L-Carnitine is beneficial for glucose oxidation

[user73636]

Acetyl-CoA and Coenzyme A (CoA) act as opposing regulators of the Pyruvate Dehydrogenase (PDH) complex, acting as a metabolic switch. Acetyl-CoA inhibits PDH to stop glucose oxidation when energy or fatty acids are plentiful, while CoA activates PDH, promoting glucose breakdown when energy is neede

Acetyl-CoA Effects on PDH (Inhibition)
Direct Product Inhibition: As a product of the PDH reaction, high levels of acetyl-CoA directly bind to the enzyme, inhibiting its activity.
Indirect Inhibition (PDK Activation): Increased acetyl-CoA/CoA ratios activate Pyruvate Dehydrogenase Kinase (PDK), which phosphorylates and inactivates PDH, decreasing carbohydrate oxidation.
Physiological State: High acetyl-CoA signals a "fed" or "fatty acid oxidation" state, preventing unnecessary glucose breakdown

Coenzyme A (CoA) Effects on PDH (Activation)
Substrate Availability: As a necessary substrate for the PDH reaction, free CoA-SH promotes the forward action of the enzyme.
Indirect Activation (PDK Inhibition): Lowered acetyl-CoA/CoA ratios (high free CoA) decrease PDK activity, allowing PDH to remain in its active, unphosphorylated state.

Heres where L carnitine comes in

L-carnitine lowers the intramitochondrial acetyl-CoA/CoA ratio by facilitating the conversion of excess acetyl-CoA into acetyl-carnitine, which is then exported out of the mitochondria. This process releases free CoA, relieving inhibition of the pyruvate dehydrogenase (PDH) complex and allowing for increased glucose oxidation and energy production.

On a high-carbohydrate, low-fat (HCLF) diet, taking carnitine primarily acts to increase glucose oxidation by further lowering the mitochondrial acetyl-CoA/CoA ratio.

While carnitine is often associated with fat burning, its role in a high-carb environment shifts toward maximizing the efficiency of carbohydrate metabolism and improving insulin sensitivity.

I think hans was right
And i think a combination of b5 and carnitine can be beneficial here with great synergy

Vitamin B5 serves as the precursor for coenzyme A (CoA) biosynthesis via the pantothenate-CoA pathway. Supplementation or adequate levels increase total CoA pools, potentially elevating free CoA and thus lowering the acetyl-CoA/CoA ratio under high acetyl load, which supports pyruvate dehydrogenase (PDH) activation and glucose oxidation .Carnitine, via carnitine acetyltransferase (CAT), reversibly transfers acetyl groups from acetyl-CoA to form acetylcarnitine, directly buffering the acetyl-CoA/CoA ratio. This reduces acetyl-CoA accumulation (e.g., from fat oxidation), relieving PDH inhibition and promoting glucose use, especially in cardiac or muscle tissue
Together, B5 expands the CoA pool while carnitine dynamically exports excess acetyl groups, synergistically maintaining a low acetyl-CoA/CoA ratio to optimize PDH activity, fatty acid oxidation balance, and redox state (NAD+/NADH). This is relevant for metabolic flexibility in conditions like exercise or nutrient stress

B5 boosts total CoA synthesis (via pantothenate kinase), raising free CoA availability to counter high-carb-induced acetyl-CoA spikes from PDH/TCA flux.
Carnitine then shuttles excess acetyl into acetylcarnitine, further lowering the inhibitory acetyl-CoA/CoA ratio and preventing PDK activation.
Moving on

L-carnitine on high-carb low-fat would generally be more favorable for optimizing the acetyl-CoA/CoA ratio compared to meldonium on high carb low-fat High-carb low-fat diets elevate pyruvate influx to PDH, generating acetyl-CoA primarily from glucose, which risks product inhibition via a high acetyl-CoA/CoA ratio—yet L-carnitine directly counters this by fueling carnitine acetyltransferase (CAT) to export acetyl as acetylcarnitine, rapidly lowering the ratio and sustaining PDH flux. In contrast, low-fat high-carb still produces some acetyl-CoA endogenously, but meldonium's carnitine depletion hampers CAT buffering, leaving acetyl-CoA/CoA higher despite reduced fatty acid input; this forces metabolic reliance on PDH indirectly but without the acute acetyl-group sink carnitine provides. Carnitine's acetyl-trap mechanism thrives precisely on high-carb conditions (pyruvate >0.25 mM), doubling PDHC activity, whereas meldonium's global fat oxidation block on a low-fat baseline offers less ratio control amid sustained glucose-derived acetyl-CoA buildup

In simple terms The Core Idea: Acetyl-CoA/CoA Ratio as a Metabolic Switch
The acetyl-CoA/CoA ratio inside mitochondria is a crucial determinant of whether pyruvate dehydrogenase (PDH) is active or suppressed.High acetyl-CoA/CoA ratio → signals energy abundance (especially from fat oxidation).
This causes:Direct PDH inhibition (product feedback).
PDK activation → PDH phosphorylation → reduced PDH activity → less glucose oxidation.
Low acetyl-CoA/CoA ratio → signals energy need or oxidative flux through glucose.
This allows:
Dephosphorylated, active PDH.Increased carbohydrate oxidation → acetyl-CoA production for the TCA cycle.
So PDH acts like a metabolic gatekeeper, determining whether pyruvate is oxidized (active) or remains in lactate and alanine (inactive).How L-Carnitine Fits In
L-Carnitine’s role isn’t only in fat transport—it also regulates acetyl buffering via the enzyme carnitine acetyltransferase (CAT):When acetyl-CoA builds up, L-carnitine helps convert acetyl-CoA to acetylcarnitine, freeing up CoA-SH. This lowers the acetyl-CoA/CoA ratio, directly relieving PDH inhibition.The exported acetylcarnitine acts like a “safety valve,” offloading excess acetyl groups to preserve mitochondrial CoA balance. So in high-carbohydrate conditions, when abundant pyruvate is converted to acetyl-CoA through PDH, carnitine maintains PDH flux and prevents bottlenecking. It’s not “burning fat” here—it’s sustaining glucose oxidation efficiency.
Why This Matters More on a High-Carb, Low-Fat Diet
In a high-carb context, most acetyl-CoA originates from pyruvate (via PDH) rather than fat. If the acetyl-CoA/CoA ratio rises too high, PDH shuts down.
L-carnitine prevents that shutdown, keeping glucose oxidation efficient.
In contrast, something like meldonium, which blocks carnitine availability, impairs this acetyl handling—even if fatty acid input is minimized—resulting in less control of mitochondrial acetyl overload.

[user73636]

I believe a stack of
B5 + carnitine + OAA/malate
High carb low fat
Eating leaner meat cuts
Lower bcaa intake
And focusing on odd chain fats (produce less acetyl coa) would be a great way to lower the acetyl coa/coa ratio further increasing the activity of pyruvate dehydrogenase
Also eat foods rich in nad precursors as the nad/nadh ratio is also important for pdh/pdk ratio

malate and OAA can not only help pull acetyl-CoA into the TCA cycle (Krebs cycle) to make energy, which frees up CoA. They also help turn NADH back into usable NAD+.
(TCA Cycle Pull)
OAA mixes with acetyl-CoA to start the cycle, releasing free CoA each turn . Malate turns into OAA inside mitochondria, keeping OAA stocked so the cycle keeps running smoothly.