To reinforce, the bright side of biotin is unlikely to be in diverting pyruvate away from lactate when its oxidation is inhibited, but in helping to process this lactate once it's taken up by normal cells.
For an idea of the extent of lactate production:
Lactate Metabolism in Patients with Metastatic Colorectal Cancer
"Using an isotope tracer technique, we found increased rates of lactate production in 20 patients with metastatic colorectal cancer [Ca] compared to 13 control subjects [C] of comparable age and sex (15.6 ± 1.3 μmol/kg/min versus 10.4 ± 0.6 μmol/kg/min; p < 0.01)."
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Their most extreme case produced lactate at 34.5 μmol/kg/min (3.48 mol/70 kg/24 h).
2 lactates per 1 glucose:
3.48 ÷ 2 → 1.74 mol/70 kg/24 h
Unit conversion:
1.74 mol/70 kg/24 h ×
180 g/mol =
313 g/70 kg/24 h
They discount the typical production based on the control group, which was 10.4 μmol/kg/min (1.05 mol/70 kg/24 h):
1.05 ÷ 2 → 0.53 mol/70 kg/24 h
Unit conversion again:
0.53 mol/70 kg/24 h × 180 g/mol =
95 g/70 kg/24 h
The difference:
313 –
95 =
218 g lactate/70 kg/24 h
However, lactate must not be a burden to normal tissues if it's widely distributed and metabolized oxidatively, because it's the catabolism of glucose continued elsewhere (glucose →→ pyruvate → lactate → pyruvate →→ carbon dioxide + water).
"When control subjects were compared to the cancer patients, no significant difference was observed in the percentage of CO2 derived from lactate oxidation (21 ± 1.6 versus 25.3 ± 1.7%)."
"The percentage of the lactate production which was immediately oxidized was not related to the rate of lactate production, the mean values in the control subjects and cancer patients being 68.3 ± 2.7 and 62.1 ± 2.4%, respectively.
"Lactate disposal by mechanisms other than immediate oxidation, i.e., the difference between the lactate production rate and the oxidation rate, was significantly increased (p < 0.001) in the cancer patients (227 ± 24 versus 128 ± 8 μmol/sq m/min or 6.0 ± 0.7 versus 3.2 ± 0.3 μmol/kg/min)."
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"The rate of nonoxidative lactate disposal was directly related to the lactate production rate (Chart 4). At least in part, conversion of lactate to glucose may account for the greater difference observed in the nonoxidative disposal in cancer patients in whom the percentage of glucose derived from lactate was significantly increased, (23.1 versus 15.8 ± 1.7%; p < 0.01). The percentage of glucose derived from lactate was also directly related to the lactate production rate (Chart 5)."
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The burden comes when lactate reforms glucose, which occurs concentrated in specific organs. Not only the synthesis of glucose from lactate consumes more energy (–6ATP) than is produced (+2ATP) in the partial breakdown of glucose, but the energy produced may be left behind where breakdown occurred, making the site of clearance an exclusive energy consumer. Yet, the body has the option to oxidize it at any time in place of glucose to avoid ATP shortage.
But an additional concern is that glycogen is found in cancer cells as well, giving them metabolic independence to maintain activity when nutrients are scarce.
Hypoxia Promotes Glycogen Accumulation through Hypoxia Inducible Factor (HIF)-Mediated Induction of Glycogen Synthase 1
Cells go through cycles of depletion and repletion, and with excess lactate around, it's possible that part of it is channeled to glycogen synthesis. Therefore, we have to wonder where glucose resynthesis (through pyruvate carboxylase) is desirable.
An assumption is that tumor lactate stems only from cancer cells, but it can be formed in surrounding cells (fibroblasts or macrophages, for example) and cancer cells may exploit it to their advantage, whether in oxidizing it or as speculated above. It's also possible to have neighboring cancer cells fermenting and respiring in cooperation.
Metabolic interplay between glycolysis and mitochondrial oxidation: The reverse Warburg effect and its therapeutic implication
This adds a layer of complication in trying to explain the benefit of nutrient supplementation with a focus on local metabolism.
