We know from Ray and other authors that thiamin, niacin, and aspirin have therapeutic potential in cancer. It seems that biotin was included in the combination without much consideration, and Jorge had access to more promising options already in his store.
I know that the priority is to nourish the person, but it's most effective when we limit nourishment to cancer cells. Biotin is a vitamin whose anabolic functions prevail, making supplementation a questionable intervention.
The assumption might have been that if pyruvate dehydrogenase (PDH) is inhibited, the alternative means to metabolize pyruvate away from lactate would be with the biotin-dependent pyruvate carboxylase (PC) to oxaloacetate.
Mitochondria are not just energy-producing organelles, they're also biosynthetic sites, with pyruvate carboxylase having an important role in this anabolic picture.
Oxaloacetate can help to export excess mitochondrial acetyl-CoA (that reinforces PDH inhibition and stimulates PC). This acetyl-CoA can then be used to synthesize fats in the cytosol, a process that's started by acetyl-CoA carboxylase (ACC)--another biotin-dependent enzyme.
Roles of pyruvate carboxylase in human diseases: from diabetes to cancers and infection
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Yes, PC-derived oxaloacetate can refill the TCA cycle, but so does ketoglutarate from glutamate or glutamine, and they can cooperate.
Two other biotin-dependent enzymes (MCC and PCC) are involved in amino acid metabolism and can also channel the products to refill the cycle. These products would enter the TCA cycle right where ATP is synthesized through substrate-level phosphorylation (Tommy), with higher chances of bypassing inhibitions.
Therefore, all 4 biotin enzymes can converge in anabolic processes that may be problematic in the context of cancer.
To compound the concerns, simple conversion of pyruvate to oxaloacetate is one step away from aspartate synthesis, needed for the upregulated nucleotide synthesis.
Maintaining cytosolic aspartate levels is a major function of the TCA cycle in proliferating cells
This aspartate can also participate in the malate-aspartate shuttle, that serves to import cytosolic NADH. Normally, oxalate is formed from malate, but if this is reversed with the help of pyruvate carboxylase, the shuttle could perhaps work in reverse, and it would contribute to the export of NADH, with higher cytosolic NADH/NAD⁺ promoting lactate synthesis. In addition, it can be an alternative way to regenerate NAD⁺ when respiratory complexes are compromised, to allow the TCA cycle to keep functioning.
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⠀(TCA cycle | Wikimedia)
In fairness, some of these processes concentrate in liver and kidneys, and biotin may also relieve the burden in supporting clearance of excess lactate from cancerous tissues (lactate → pyruvate –B7→ oxaloacetate → pyruvate enolphosphate →→ glucose), possibly more so than thiamin, as local pyruvate oxidation without redistribution as glucose could perhaps overwhelm such organs. However, thiamin could be of better service for other tissues, that clear lactate through complete oxidation.
Even in cases where biotin supplementation normalizes glucose metabolism, the anabolic component can't be discarded.
Some Aspects of Carbohydrates Metabolism in Biotin-Deficient Rats
"It is possible, therefore, that these changes in the fatty acid composition of the lipid might alter the structural integrity of mitochondria with the consequent effect on oxidative phosphorylation. This defect, as reflected by amino acid incorporation studies, was compensated during early stages of the deficiency when the animals received an oxidizable substrate such as succinate (see reference 1) or fructose or sorbitol in the basal diet. It is, therefore, possible that a moderate decrease in oxidative phosphorylation does not limit the efficiency of the biotin-deficient animal as long as adequate levels of oxidizable substrates are maintained. However, in advanced deficiency as observed after 8 weeks on the deficient diet, succinate, sorbitol, or fructose feeding did not help the animal. Only administration of biotin restwed fatty acid synthesis and the integrity of mitochondria for normal oxidative phosphorylation."
It's no wonder that symptoms of biotin deficiency point to anabolic defects, such as disturbed skin lipids.
I would be careful with its supplementation in advanced cancer and observe reactions. It's preferable to avoid B-vitamins formulas and have the vitamins separately for better control.
This is not to suggest that thiamin, niacin, and aspirin are entirely beneficial in cancer because they're not, but their positive outweigh negative effects. Biotin isn't invariably problematic, but seems riskier.
