GcMAF (or Gc protein-derived macrophage activating factor) is a protein produced by modification of vitamin D-binding protein. Proponents of GcMAF claim that it is an immunomodulatory protein that has antitumor properties and strengthens the immune system by macrophage activation. Organizations including Cancer Research UK have issued warnings informing the public that there is no reliable evidence that GcMAF is effective.
Biochemically, GcMAF results from sequential deglycosylation of the vitamin D-binding protein (the Gc protein), which is naturally promoted by lymphocytes (B and T cells). The resulting protein may be a macrophage activating factor (MAF). MAFs are lymphokines that control the expression of antigens on the surface of macrophages, and one of their functions is to make macrophages become cytotoxic to tumors.
In 2008 claims were made that GcMAF can provide a permanent cure for cancer and HIV by activating macrophage white blood cell production. These claims have been the subject of criticism. The papers supporting the claims have since been retracted by the journals in which they were published. Consumers have been warned about illegal marketing of the substance over the internet. The Belgian Anticancer Fund has communicated serious concerns to other journals that published studies on GcMAF by Yamamoto and colleagues.[which?] 
GcMAF has been promoted as a cure for cancer, HIV, autism and other conditions. The integrity of the research, conducted by Nobuto Yamamoto and colleagues, that originally prompted claims regarding cancer and HIV has been questioned. Cancer Research UK has warned the public about spurious claims of clinical benefits, misleadingly based on reduced levels of the alpha-N-acetylgalactosaminidase enzyme (also known as nagalase), whose production might be increased in many cancers. Nagalase is an enzyme present in normal cells and its use to diagnose or follow-up the diseases claimed to be cured by GcMAF has not been validated. Nagalase deficiency, however, is associated to a rare congenital metabolic disorder called Schindler/Kanzaki disease.
Three out of four of the original studies authored by Yamamoto (published between 2007 and 2009) were retracted by the scientific journals in which they were published in 2014, officially due to irregularities in the way ethical approval was granted. Retraction reasons also included methodological errors in the studies.
A Japanese clinic reported its experience with three patients out of a total of 345 patients they treated with GcMAF in combination with other alternative therapies, this report was published in 2013, and concluded that observations were "hopeful".
They also published a case report that described the case of a breast cancer patient treated with GcMAF, other alternative therapies and standard of care (exemestane), the evolution was favorable.
- Galactosidases — Advances in Research and Application. Scholarly Editions. 21 June 2013. p. 52. ISBN 978-1-4816-8801-7.
- Inui, Makita, Miura, Matsuda, Kuchiike, Kubo, Mette, Uto, Nishikata, Hori, Sakamoto (2014). "Case report: A breast cancer patient treated with GcMAF, sonodynamic therapy and hormone therapy". Anticancer Research. 34: 4589–93. PMID 25075104.
- Malik, Suneil; Fu, Lei; Juras, David James; Karmali, Mohamed; Wong, Betty Y. L.; Gozdzik, Agnes; Cole, David E. C. (January–February 2013). "Common variants of the vitamin D binding protein gene and adverse health outcomes". Critical Reviews in Clinical Laboratory Sciences. 50 (1): 1–22. PMC . PMID 23427793. doi:10.3109/10408363.2012.750262.
- Arney, Kat (3 December 2008). "'Cancer cured for good?' – Gc-MAF and the miracle cure (revised 25 July 2014)". Cancer Research UK. Retrieved 10 February 2015.
- Mosser, David M. (February 2003). "The many faces of macrophage activation". Journal of Leukocyte Biology. 73 (2): 209–212. PMID 12554797. doi:10.1189/jlb.0602325.
- "GCMAF". Anticancer Fund. 24 July 2014. Retrieved 2014-07-26.
- "Tracking retractions as a window into the scientific process Yet another study of widely touted cancer "cure" retracted". Retraction Watch. Retraction Watch. Retrieved 28 July 2015.
- (Retracted) Yamamoto, Nobuto; Ushijima, Naofumi; Koga, Yoshihiko (January 2009). "Immunotherapy of HIV-infected patients with Gc protein-derived macrophage activating factor (GcMAF)". Journal of Medical Virology. 81 (1): 16–26. PMID 19031451. doi:10.1002/jmv.21376.
- Miller, Michael E. (16 July 2015). "The mysterious death of a doctor who peddled autism ‘cures’ to thousands". Washington Post. Retrieved 26 August 2015.
- (Retracted) Yamamoto, Nobuto; Suyama, Hirofumi; Yamamoto, Nobuyuki; Ushijima, Naofumi (15 January 2008). "Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (GcMAF)". International Journal of Cancer. 122 (2): 461–467. doi:10.1002/ijc.23107.
- Yamamoto, N.; Suyama, H.; Nakazato, H.; Yamamoto, N.; Koga, Y. (2014). "Retraction Note to: Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF". Cancer Immunology, Immunotherapy. 63 (12): 1349. doi:10.1007/s00262-014-1616-x.
- "Retraction". International Journal of Cancer. 135 (6): 1509. 15 September 2014. doi:10.1002/ijc.29014.
- Ivan Oransky (25 July 2014). "Paper about widely touted but unapproved "cure" for cancer, autism retracted". Retractionwatch.
- Toshio Inui, Daisuke Kuchiike, Kentaro Kubo, Martin Mette, Yoshihiro Uto, Hitoshi Hori And Norihiro Sakamoto (2013). "Clinical Experience of Integrative Cancer Immunotherapy with GcMAF". Anticancer Research.
- Pacini, Stefania; Punzi, Tiziana; Morucci, Gabriele; Gulisano, Massimo; Ruggiero, Marco (1 December 2011). "Effects of Vitamin D-binding Protein-derived Macrophage-activating Factor on Human Breast Cancer Cells". International Journal of Cancer Research and Treatment.
- Ruggiero, Marco; Pacini, Stefania; Morucci, Gabriele; Branca, Jacopo; Ward, Emma (22 August 2013). "Effects of Vitamin D-binding Protein-derived Macrophage-activating Factor on Human Breast Cancer Cells". Frontiers in Immunology. 4. doi:10.3389/conf.fimmu.2013.02.00221.
- "International Journal of Cancer Research (Int J Canc Res)". Academic Journals. Retrieved 18 January 2015.
- Mollie Bloudoff-Indelicato (23 October 2015). "Backlash after Frontiers journals added to list of questionable publishers". Nature.