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IV Alpha Lipoic Acid

What is IV ALA?

IV alpha lipoic acid (ALA) is used to treat cancer, neuropathy and chronic liver disease. This fatty acid is a natural, yet powerful antioxidant, like vitamin C and E, found in many foods and helps protect cells from oxidative damage.

 

IV ALA for Cancer

We use IV ALA administration for cancer at our clinic for our patients. Yet, Dr. Burton Berkson and D. Rubin are pioneers of this alternative treatment for cancer patients. Burton and Rubin describe the long-term survival of a patient with pancreatic cancer with liver metastasis using intravenous alpha-lipoic acid and low-dose naltrexone orally (Berkson et al. 2006). The patient was told by a reputable university oncology center that there was little hope for his survival. The patient, with the above treatment, is alive and well 78 months after initial presentation. The authors report he is back at work, free from symptoms, and without appreciable progression of his malignancy.

 

Since the first case, the authors report 3 other cases of pancreatic cancer with metastasis and report one is alive and well 39 months after diagnosis, and the other two cases have had PET scans after 4-5 months of therapy that show no evidence of disease (Berkson et al. 2009). Ultimately, the benefits of using IV alpha lipoic acid for cancer treatment include:

  • an agent that reduces oxidative stress
  • its ability to stabilize NF(k)B (a protein complex that regulates DNA transcription)
  • its ability to stimulate pro-oxidant cancer cell death
  • its discriminative ability to discourage the proliferation of malignant cells
  • the ability of low dose naltrexone to modulate an endogenous immune response

 

However, ALA has also been used to treat other forms of cancer as well. ALA, in particular, protects against the death of normal cells from oxidative stress while inducing cell death in cancer cells. In colon cancer cells, this fatty acid enhances the uptake of oxidizable substrates into mitochondria, increasing oxidative stress and inducing apoptosis (i.e. cell death) in tumours (Wenzel et al. 2005). Furthermore, ALA also mediates cell death in lung cancer cells by regulating oxidative stress (Moungjaroen et al. 2006). Likewise, ALA induces apoptosis is via different biochemical pathways in lung cancer cells. Choi et al. (2009) demonstrate that ALA upregulates the caspase-dependent pathway mediated by Ca2+ as well as the caspase-independent pathways mediated by PARP (poly-ADP-ribose polymerase).

 

Other cancers that may benefit from use of IV ALA include:

  • Brain and spinal cord (specifically astroglial) (Flier et al. 2009)
  • Endometrium (Mantovani et al. 2000)
  • Head and neck (Mantovani et al. 2000)
  • Liver (Shi et al. 2008)
  • Leukemia (Dovinova et al. 1999, Pack et al. 2002)
  • Ovary (Mantovani et al. 2000)

 

Is it safe?

We’ve administered dozens of IV Alpha Lipoic Acid treatments safely at the clinic. Preparation of the IV is important as alpha lipoic acid is destroyed by light so it is delivered with protection of the IV bag from light exposure. The most severe reactions we’ve experienced are patients feeling nausea following the treatment, which clears in a short time after the therapy. In fact, IV ALA is often used to reduce the side effects of other cancer treatments.

 

Although chemotherapy is a life-saving form of treatment, a common side effect is neurotoxicity leading to peripheral neuropathy. A neuropathy gives rise to a set of symptoms from damage to the nerves controlling how our arms and legs feel and move. Typically, peripheral neuropathies stop once chemotherapy treatment has finished and neurotoxicity is reduced, but the symptoms may also last for years. However, IV ALA can be used to reduce the neuropathic pain as a side effect of chemotherapy drugs (Gedlicka et al. 2002 and 2003; Melli et al. 2008).

 

Diarrhea is another common side effect of chemotherapy – in fact, up to 50-80% of treated patients will experience this symptom because of therapy (Stein et al. 2010). Chemotherapy drugs like methotrexate often induce intestinal toxicity due to oxidative stress and DNA damage leading to intestinal cell toxicity (Dadhania et al. 2010). As such, using ALA prior to chemotherapy helps protect against intestinal toxicity and improve the consistency of stool (Dadhania et al. 2010).

 

A lesser known side effect of chemotherapy drugs is cardiac toxicity. Cardiotoxicity is typically rare, yet may occur in more than 20% of patients treated with doxorubicin, daunorubicin or fluorouracil (Pai and Nahata 2000). Pai and Nahata (2000) describe the following cardiac events that may occur as a result of such chemotherapy drugs: mild blood pressure changes, thrombosis, electrocardiographic changes, arrhythmias, myocarditis, pericarditis, myocardial infarction, cardiomyopathy, cardiac failure (left ventricular failure) and congestive heart failure (Pai and Nahata 2000). ALA not only ameliorates these symptoms (Al-Majed et al. 2002) but is also protective against the onset of cardiotoxicity (Balachandar et al. 2003).

 

Likewise, chemotherapy drugs like adriamycin and chloroquine can also cause kidney toxicity. Nonetheless, high doses and prolonged use of any chemotherapy drug increases the risk of kidney damage, regardless if the patient is at risk of kidney injury (de Jonge and Verweij 2006, Finkel and Foringer 2007, Humphreys et al. 2005, Lameire et al. 2005, Perazella and Moeckel 2010). As such, several studies have demonstrated that ALA is protective against chemotherapy-induced kidney damage (Malarkodi et al. 2003a, b, c, d; Murugavel and Pari 2004).

 

References

Al-Majed, A. A., Gdo, A. M., Al-Shabanah, O. A., et al. (2002) Alpha-lipoic acid ameliorates

myocardial toxicity induced by doxorubicin. Pharmacol Res. 46(6):499–503.

 

Balachandar, A. V., Malarkodi, K. P., and Varalakshmi, P. (2003) Protective role of DLalpha-lipoic

acid against adriamycin-induced cardiac lipid peroxidation. Hum Exp Toxicol. 22(5):249–

54.

 

Berkson, B. M., Rubin, D. M., and Berkson, A. J. (2006) The long-term survival of a patient with

pancreatic cancer with metastases to the liver after treatment with the intravenous

alpha-lipoic acid/low-dose naltrexone protocol. Integr Cancer Ther. 5(1):83–9.

 

Berkson, B. M., Rubin, D. M., and Berkson, A. J. (2009) Revisiting the ALA/N (alpha-lipoic acid/low-

dose naltrexone) protocol for people with metastatic and nonmetastatic pancreatic

cancer: a report of 3 new cases. Integr Cancer Ther. 8(4):416–22.

 

Choi, S. Y., Yu, J. H., and Kim, H. (2009) Mechanism of alpha-lipoic acid-induced apoptosis of lung

cancer cells. Ann N Y Acad Sci. 1171:149–55.

 

Dadhania, V. P., Tripathi, D. N., Vikram, A., et al. (2010) Intervention of alpha-lipoic acid

ameliorates methotrexate-induced oxidative stress and genotoxicity: A study in rat

intestine. Chem Biol Interact. 183(1):85–97.

 

de Jonge, M. J. A. and Verweij, J. (2006) Renal toxicities of chemotherapy. Semin Oncol. 33:68–

73.

 

Dovinova, I., Novotny, L., Rauko, P., et al. (1999) Combined effect of lipoic acid and doxorubicin

in murine leukemia. Neoplasma46:237–41.

 

Finkel, K. W. and Foringer, J. R. (2007) Renal disease in patients with cancer. Nat Clin Pract

Nephrol3:669–78.

 

Flier, J., Van Muiswinkel, F. L., Jongenelen, C. A., et al. (2002) The neuroprotective antioxidant

alpha-lipoic acid induces detoxication enzymes in cultured astroglial cells. Free Radic Res.

36:695–9.

 

Gedlicka, C., Scheithauer, W., Schull, B., a et al. (2002) Effective treatment of oxaliplatin-induced

cumulative polyneuropathy with alpha-lipoic acid. J Clin Oncol. 20:3359–61.

 

Gedlicka, C., Kornek, G. V., Schmid, K., et al. (2003) Amelioration of docetaxel/cisplatin induced

polyneuropathy by alpha-lipoic acid. Ann Oncol. 14:339–40.

 

Humphreys, B. D., Soiffer, R. J., and Magee, C. C. (2005) Renal failure associated with cancer and

its treatment: An update. J Am Soc Nephrol. 16:151–61.

 

Lameire, N. H., Flombaum, C. D., Moreau, D., et al. (2005) Acute renal failure in cancer patients.

Ann Med. 37:13–25.

 

Mantovani, G., Macciò,A.,Melis, G., et al. (2000) Restoration of functional defects in peripheral

blood mononuclear cells isolated from cancer patients by thiol antioxidants alpha-lipoic

acid and N-acetyl cysteine. Int J Cancer. 86:842–7.

 

Malarkodi, K. P., Balanchandar, A. V., and Varlakshmi. P. (2003a) The influence of lipoic acid on

adriamycin induced nephrotoxicity in rats. Mol Cell Biochem. 247:15–22.

 

Malarkodi, K. P., Balanchandar, A. V., and Varlakshmi. P. (2003b) The influence of lipoic acid on

adriamycin-induced hyper-lipidemic nephrotoxicity in rats. Mol Cell Biochem. 247:139–

45.

 

Malarkodi, K. P., Balanchandar, A. V., and Varlakshmi. P. (2003c) Protective effect of lipoic acid

on adriamycin-induced lipid peroxidation in rat kidney. Mol Cell Biochem. 247:9–13.

 

Malarkodi, K. P., Balanchandar, A. V., Sivaprasad, R., et al. (2003d) Prophylactic effect of lipoic

acid against adriamycin-induced peroxidative damages in rat kidney. Ren Fail25:367–77.

 

Melli, G., Taiana, M., Camozzi, F., et al. (2008) Alpha-lipoic acid prevents mitochondrial damage

and neurotoxicity in experimental chemotherapy neuropathy. Exp Neurol. 214(2):276–84.

 

Moungjaroen, J., Nimmannit, U., Callery, P. S., et al. (2006) Reactive oxygen species mediate

caspase activation and apoptosis induced by lipoic acid in human lung epithelial cancer

cells through Bcl-2 down-regulation. J Pharmacol Exp Ther319:1062–9.

Murugavel, P. and Pari, L. (2004) Attenuation of chloroquine-induced renal damage by alpha-

lipoic acid: possible antioxidant mechanism. Ren Fail. 26(5):517–24.

 

Pack, R.A., Hardy, K., Madigan, M. C., et al. (2002) Differential effects of the antioxidant alpha-

lipoic acid on the proliferation of mitogen-stimulated peripheral blood lymphocytes and

leukaemic T cells. Mol Immunol. 38:733–45.

 

Pai, V. B. and Nahata, M. C. (2000) Cardiotoxicity of chemotherapeutic agents: incidence,

treatment and prevention. Drug Saf. 22(4):263–302.

 

Perazella, M. A. and Moeckel, G. W. (2010) Nephrotoxicity from chemotherapeutic agents:

Clinical manifestations, pathobiology, and prevention/therapy. Semin Nephrol. 30:570–

81.

 

Shi, D. Y., Liu, H. L., Stern, J. S., et al. (2008) Alpha-lipoic acid induces apoptosis in hepatoma cells

via the PTEN/Akt pathway. FEBS Lett. 582:1667–71.

 

Stein, A., Voigt, W., and Jordan, K. (2010) Chemotherapy-induced diarrhea: pathophysiology,

frequency and guideline-based management. Ther Adv Med Oncol. 2(1):51–63.

 

Wenzel, U., Nickel, A., and Daniel, H. (2005) alpha-Lipoic acid induces apoptosis in human colon

cancer cells by increasing mitochondrial respiration with a concomitant O2-*-

generation. Apoptosis. 10(2):359–68.