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.
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).
“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.”
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.
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:
Pantothenic acid → 4’-phosphopantothenate (by pantothenate kinase, the rate-limiting enzyme).
Series of steps → Coenzyme A.
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.
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).
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.
Apparently pantothenic acid but not pantethine crosses the BBB:
Pantothenic Acid Transport Through the Blood-Brain Barrier 1986: “Thus, PA is transported through the blood-brain barrier by a lowcapacity, saturable transport system with a half-saturation concentration -10 times the plasma PA concentration. Although involved in the transfer of PA from blood into brain, this system does not play an important regulatory role in the synthesis of CoA from PA in brain.”
The decline in adult stem cell performance is closely linked to tissue malfunction and the rising incidence of age-related diseases. To investigate the molecular basis of these impairments, our screening strategy identified reduced activity in the pantothenate/coenzyme A (CoA) pathway within aged ISCs. Furthermore, exogenous CoA supplementation restructured ISC metabolic pathways, reversing age-induced hyperproliferation and intestinal dysfunction, and thus extending Drosophila lifespan by curbing excessive iron accumulation in ISCs. These findings uncover a new mechanism of stem cell aging and propose that pantothenate and CoA could be potential therapeutic targets for treating age-related diseases and enhancing healthy aging in humans.
To demonstrate the impact of CoA on Drosophila ISC function in aging flies, we assessed the suppressive effects on age-related accumulation of esg+ cells utilizing an “esg-luciferase” reporter system (Fig 1A and 1B). Supplementing with pantothenate, a precursor to CoA or CoA starting at a moderate age (26 days) demonstrated a significant inhibitory impact on the esg-expressing cells accumulation in the midguts of older (40 days) flies (Fig 1C and 1D). In our investigation, we examined three different concentrations of pantothenate supplementation (0.1, 1, and 10 mM), and determined that 1 mM pantothenate, was efficacious in suppressing esg+ cell accumulation in aged midguts, as evidenced by a substantial reduction in luciferase activity (Fig 1C). Furthermore, our findings revealed that supplementing with 0.5 mM of CoA was similarly effective in inhibiting the esg+ cells’ accumulation within the aged flies’ midguts (Fig 1D). Thus, we selected a drug concentration of 1mM for pantothenate and 0.5 mM for CoA in the following experiments
Moreover, CoA supplementation significantly rescued the ISC differentiation capability of flies with dPANK/fbl depletion as indicated by NRE-lacZ staining (Fig 3D–3H) and esg-GFP+Pros+ staining (Figs 3E–3H and S1I). However, pantothenate supplementation failed to mitigate the ISC accumulation and disruption in differentiation ability triggered by dPANK/fbl deficiency in these young flies (Figs 3B–3H and S1D–S1I).
I am in a bar following a gig so I don’t have my usual records access, but some of the v early lifespan experiments were with the CoA B5 pathway. A lot of this has been forgotten.
Pantothenate kinases (PANKs), which regulate the first and rate-limiting step of coenzyme A (CoA) biosynthesis, have emerged as therapeutic targets for various human diseases. PANKs family consists of PANK1, PANK2, PANK3, and PANK4. We summarized the research progress of the PANK family in the last two decades. Notably, PANKs play critical roles in diverse pathophysiological mechanisms underlying human diseases, including pantothenate kinase-associated neurodegeneration (PKAN), propionic acidemia ¶, lipid metabolic disorders, Parkinson’s disease (PD), glioma, clear cell renal cell carcinoma (ccRCC), and insulin resistance (IR). Nevertheless, the precise relationship between PANKs and human diseases remained ambiguous. Therefore, this review provides a comprehensive summary of the structural properties, molecular mechanisms, and relevant modulators that govern PANK activity. In conclusion, targeting PANKs as regulators of CoA biosynthesis and disease pathogenesis contributes to connecting biochemistry with pharmacotherapy.
Through high-throughput virtual screening, this work identifies Pantethine as a potent PSMD14 activator that enhances deubiquitinase activity, restores SLC7A11 expression in osteocytes, and mitigates osteoporosis.
We found that autoreactive encephalitogenic T cells display an altered coenzyme A (CoA) synthesis pathway, compared to resting T cells. CoA fueling with the CoA precursor pantethine (PTTH) affected essential immune-related processes of myelin-specific T cells, such as cell proliferation, cytokine production, and cell adhesion, both in vitro and in vivo. Accordingly, pre-clinical treatment with PTTH before disease onset inhibited the development of EAE by limiting T cell pro-inflammatory potential in vivo. Importantly, PTTH also significantly ameliorated the disease course when administered after disease onset in a therapeutic setting. Finally, PTTH reduced pro-inflammatory cytokine production by human T helper 1 (Th1) and Th17 cells and by T cells from MS patients, confirming its translational potential.
Our data demonstrate that CoA fueling with PTTH in pro-inflammatory and autoreactive T cells may represent a novel therapeutic approach for the treatment of autoimmune neuroinflammation. We thus propose that PTTH supplementation may serve as an adjuvant treatment in MS and other human neuroinflammatory and autoimmune disorders in combination with disease-modifying drugs, in order to boost their overall efficacy.
The point about Pantethine is that it is following the rate limiting step in the CoA creation pathway. That could be an issue at high levels, but I have not noticed anything negative from 4-5 grams. It may extend bruising, however.
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.
Summary of Key Points:
