There are several ways to jumpstart mitochondrial activity. The first is to correct this gigantic metabolic traffic jam which characterizes the cancer cell. The mitochondria cannot burn and release entropy in the form of heat because the nutrient does not reach the mitochondria. There is a protein, called pyruvate dehydrogenase (PDH). It allows the passage of pyruvate, the main breaking down product of glucose, to the mitochondria to be transformed into Acetyl-CoA. If PDH is blocked, pyruvate cannot be burnt by the mitochondria. This provokes an accumulation of pyruvate that will take another path and will be excreted in the form of lactic acid. This is the Warburg effect. Another metabolic pathway will also open up, called the pentose phosphate pathway by specialists. It will lead to the synthesis of building blocks (DNA, proteins, etc.) that makes growth possible. The disconnection of the mitochondria due to inactivated PDH results in tumor growth.
PDH is not a simple protein, it is a complex of multiple subunits. In other words, a nightmare for a biochemist! One of the 12 cofactors of this complex is a drug frequently prescribed in Northern Europe: α-lipoic acid. The addition of α-lipoic acid stimulates PDH leading to the degradation of the pyruvate by the mitochondria that was simply “disconnected”. Dozens of scientific publications describe the anti-tumor efficacy of this drug. If the mitochondria start functioning again, it will generate heat as entropy by burning pyruvate. As a direct consequence, growth will slow down.
In cancer, the mitochondria cannot burn glucose. In addition, it leaks citrate which will be exported to make cell membranes. Citrate, an acid substance present, in large quantities, in citrus fruits, especially in lemon, leaves the mitochondria to go into the surrounding cytoplasm. To counteract this leak of citrate, another key enzyme, citrate lyase, must be blocked with hydroxycitrate.
If the non-scientific reader ignores the technical terms, the demonstration may seem elementary. However, it took more than ten years to develop it and several more years of experimentation, not to mention the sacrifice of nearly 20,000 mice! We would like to point out to sensitive people that medical research unfortunately does not yet make it possible to do without animal experimentation. But researchers limit the use of mice as much as possible, which constitute 4/5 of the animals used in the research.
Injecting tumor cells into the flank of mice turns into a palpable tumor within days, and the mouse dies within weeks. Treatment with α-lipoic acid or hydroxycitrate, taken alone, had little effect. On the other hand, the combination of the two products is extremely effective in slowing the growth of cancers of all types (bladder, colon, lung, cutaneous melanoma, etc.).
Like any other citizen, the doctor must respect the law. He can only conduct therapeutic trials within the regulated framework of institutions. However, another law in some countries and a few of the states in the United States, and not the least, stipulates “assistance to person in danger”. When a physician knows his patient has a short life expectancy, but thinks that treatment can extend his life under the right conditions, he wants to do the impossible. Unfortunately, oncologists, are caught between two fires, the upcoming death of the patient and the absence of effective treatment.
Legally, α-lipoic acid is both a drug (there is an intravenous form) and a dietary supplement in oral form. The hydroxycitrate is sold as a dietary supplement. These two molecules have already been prescribed separately to hundreds of thousands of patients.
Lipoic acid is over sixty years old. It is an effective treatment for complications of diabetes with effects confirmed by multiple clinical trials. It is manufactured by well-established manufacturers, and can be obtained without a prescription in pharmacies in Germany, Austria or Andorra where it is prescribed larga manu. On the other hand, it cannot be found in France. No longer benefiting from the protection proper to patents, no French industrialist wants to pay registration fees to produce it if it is not assured of a “legal monopoly”.
Contrary to popular belief, hydroxycitrate does help with weight loss, though it is still sold as an appetite suppressant. We advised patients the same prescribed doses to treat other illnesses.
It is not science, but caution. Italian colleagues had done the same and observed both an absence of toxicity and unexpected results, which they had also published in a peer-reviewed journal.
Baronzio, G., Schwartz, L., Crespi, E., Guais, A., Sanders, E., Delépine, N., & Fiorentini, G. (2012). Early clinical and toxicological results of a combination of natural glycolysis inhibitors (METABLOC™) on cancer patients. Biomedical Research, 23, 219-222.
In these preliminary studies, the treatment is as follows:
- Lipoic acid: 800 mg in tablets morning and evening
- Hydroxycitrate: 500 mg in tablets, morning, noon and evening
Lipoic (or α-lipoic) acid and hydroxycitrate can be found in pharmacies or online. Hydroxycitrate is extracted from an exotic fruit, Garcinia cambodgia or the Malabar tamarind tree. It looks like a pumpkin and is high in hydroxycitrate. Hoffmann-la Roche, a large Swiss pharmaceutical company, proposed it to treat obesity fifty years ago, but due to lack of efficacy for obesity treatment had to stop its marketing. Pure hydroxycitrate is not commercially available. This has forced patients to take a dietary supplement rich in 60% hydroxycitrate, the remaining 40% consisted of salt and excipient (other inactive ingredients).
This treatment has no major side effect. Some patients have complained of fleeting discomfort. Contrary to the usual history of cancer patients, the addition of low doses of oral chemotherapy has enabled them to pass the milestone and survive in acceptable conditions. It may not be a panacea, but it is already a huge step forward.
Schwartz, L., Buhler, L., Icard, P., Lincet, H., Summa, G. M., Steyaert, J. M. (2014). Metabolic cancer treatment: Intermediate results of a clinical study. Cancer Ther, 10, 13-19.