Leukemia Supplement Recommendations

Multiple nutritional supplements have been associated with reduced cancer occurrence and/or cancer progression. The list below contains those with the greatest evidence-base and benefit, though it is not necessary that they all be included.

Vitamin D

  • Human trials have shown that low levels of vitamin D are related to a higher risk of developing leukemia and also with a worsening prognosis following a diagnosis of AML.[1] Increased vitamin D level was associated with higher survival rate in elderly patients with acute myeloid leukemia.[2] Individuals with a history of lymphoma should also monitor 1,25 dihydroxy-vitamin D levels, as rapid conversion to this active form has been observed in patients with lymphoma.
  • Suggested dose is that sufficient to raise vitamin D blood levels to >40 ng/mL, which may require 5000 IU per day or more.[3]

Grape seed extract

  • Grape seed extract used on leukemia cell lines decreased uncontrolled cell proliferation and survival and increase cell death in leukemia cells.[4],[5] Other studies indicate that the antioxidant in grape seeds called proanthocyanidins are likely to induce monocytic differentiation in leukemia cells (which prevents proliferation).[6],[7]
  • Suggested dose: 500 mg of a 90% OPC extract.

Cordyceps

  • Cordyceps is a fungus which has shown promising effects on immune stimulation, including aiding in cancer cell death. In cell studies, this plant induced apoptosis (programmed cell death) in human promyelocytic leukemia cells.[8] More recently cell studies have shown that cordyceps specifically suppresses proliferation in leukemia cells.[9]
  • Suggested dose: 3 to 6 grams per day.

DIM & Isothiocyanates

  • Isothiocyanates, which are abundant in cruciferous vegetables, like broccoli, cauliflower and cabbage, have shown anti-tumor activity as well as DIM (3,3′-Diindolylmethane), also found in these same vegetables. Treatment of the T-ALL human cell lines CCRF-CEM, CCRF-HSB2, SUP-T1 and Jurkat with DIM in vitro significantly reduced cell proliferation and viability.[10] Other animal cell studies demonstrated that DIM induced cell death in myeloid cell leukemia.[11]
  • Suggested dose: DIM 250mg & Isothiocyanates 600mcg per day.

Curcumin

  • The active extract from the spice turmeric, curcumin, has been shown to cause cell death in a variety of cancer cell lines. In trials with the human acute leukemia cell line THP-1, curcumin inhibited proliferation and induced apoptosis of these cancer cells.[12]
  • Suggested dose: 1-2g per day of Meriva® or Longvida® curcumin.[13],[14]

Olive Leaf Extract

  • Olive leaf contains the antioxidants oleuropein and hydroxytyrosol, which are believed to have anti-cancer affects. Olive leaf extracts induced apoptosis (programmed cell death) as well as induction of differentiation (moving them toward a more normal phenotype) of human leukemia cells.[15],[16]
  • Suggested dose: 250 to 500 mg of a standardized extract, 1-3 times per day.

Green tea extract

  • Catechins, antioxidants found in green tea, particularly EGCG (epigallocatechin-3-gallate), are known to have many anti-tumor affects. In human adult T-cell leukemia cells, ECGC reduced cancer cell proliferation.[17] In animal studies of leukemia cells, a similar mechanism of tumor cell death was found.[18]
  • Suggested dose: 1g EGCG and mixed catechins.

Milk thistle

  • Silymarin and silibinin from milk thistle have anti-proliferative and anti-metastatic properties, and may reduce the liver damaging effects of chemotherapy, especially in children. In children with ALL and liver toxicity, milk thistle was associated with a trend toward significant reductions in liver toxicity.[19]
  • Suggested dose: At least 500mg silymarin per day.

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[1] Lee HJ, Muindi JR, Tan W, Hu Q, Wang D, Liu S, Wilding GE, Ford LA, Sait SN, Block AW, Adjei AA, Barcos M, Griffiths EA, Thompson JE, Wang ES, Johnson CS, Trump DL, Wetzler M. Low 25(OH) vitamin D3 levels are associated with adverse outcome in newly diagnosed, intensively treated adult acute myeloid leukemia. Cancer. 2014 Feb 15;120(4):521-9. doi: 10.1002/cncr.28368. Epub 2013 Oct 25.

[2] Paubelle E, Zylbersztejn F, Alkhaeir S, Suarez F, Callens C, Dussiot M, Isnard F, Rubio MT, Damaj G, Gorin NC, Marolleau JP, Monteiro RC, Moura IC, Hermine O. Deferasirox and vitamin D improves overall survival in elderly patients with acute myeloid leukemia after demethylating agents failure. PLoS One. 2013 Jun 20;8(6):e65998. doi: 10.1371/journal.pone.0065998. Print 2013.

[3] Garland CF, French CB, Baggerly LL, et al. Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention. Anticancer Res. 2011 Feb;31(2):607-11.

[4] Espino J, González-Gómez D, Moreno D, Fernández-León MF, Rodríguez AB, Pariente JA, Delgado-Adámez J. Tempranillo-derived grape seed extract induces apoptotic cell death and cell growth arrest in human promyelocytic leukemia HL-60 cells. Food Funct. 2013 Dec;4(12):1759-66.

[5] Gao N, Budhraja A, Cheng S, Yao H, Zhang Z, Shi X. Induction of apoptosis in human leukemia cells by grape seed extract occurs via activation of c-Jun NH2-terminal kinase. Clin Cancer Res. 2009 Jan 1;15(1):140-9. doi: 10.1158/1078-0432.CCR-08-1447.

[6] Wang M, Wang L, Pan XJ, Zhang H. Monocytic differentiation of K562 cells induced by proanthocyanidins from grape seeds. Arch Pharm Res. 2012 Jan;35(1):129-35.

[7] Hu H, Qin YM. Grape seed proanthocyanidin extract induced mitochondria-associated apoptosis in human acute myeloid leukaemia 14.3D10 cells. Chin Med J (Engl). 2006 Mar 5;119(5):417-21.

[8] Zhang QX, Wu JY. Cordyceps sinensis mycelium extract induces human premyelocytic leukemia cell apoptosis through mitochondrion pathway. Exp Biol Med (Maywood). 2007 Jan;232(1):52-7.

[9] Ko BS, Lu YJ, Yao WL, Liu TA, Tzean SS, Shen TL, Liou JY. Cordycepin regulates GSK-3β/β-catenin signaling in human leukemia cells. PLoS One. 2013 Sep 26;8(9):e76320. doi: 10.1371/journal.pone.0076320. eCollection 2013.

[10] Shorey LE, Hagman AM, Williams DE, Ho E, Dashwood RH, Benninghoff AD. 3,3′-Diindolylmethane induces G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia cells. PLoS One. 2012;7(4):e34975. doi: 10.1371/journal.pone.0034975. Epub 2012 Apr 13.

[11] Gao N, Cheng S, Budhraja A, Liu EH, Chen J, Chen D, Yang Z, Luo J, Shi X, Zhang Z. 3,3′-Diindolylmethane exhibits antileukemic activity in vitro and in vivo through a Akt-dependent process. PLoS One. 2012;7(2):e31783. doi: 10.1371/journal.pone.0031783. Epub 2012 Feb 21.

[12] Guo Y, Shan Q, Gong Y, Lin J, Shi F, Shi R, Yang X. Curcumin induces apoptosis via simultaneously targeting AKT/mTOR and RAF/MEK/ERK survival signaling pathways in human leukemia THP-1 cells. Pharmazie. 2014 Mar;69(3):229-33.

[13] Marczylo TH, Verschoyle RD, Cooke DN, et al. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine. Cancer Chemother Pharmacol. 2007 Jul;60(2):171-7

[14] DiSilvestro RA1, Joseph E, Zhao S, Bomser J. Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J. 2012 Sep 26;11:79. doi: 10.1186/1475-2891-11-79.

[15] Samet I, Han J, Jlaiel L, Sayadi S, Isoda H. Olive (Olea europaea) leaf extract induces apoptosis and monocyte/macrophage differentiation in human chronic myelogenous leukemia K562 cells: insight into the underlying mechanism. Oxid Med Cell Longev. 2014;2014:927619.

[16] Abaza L, Talorete TP, Yamada P, Kurita Y, Zarrouk M, Isoda H. Induction of growth inhibition and differentiation of human leukemia HL-60 cells by a Tunisian gerboui olive leaf extract. Biosci Biotechnol Biochem. 2007 May;71(5):1306-12.

[17] Harakeh S, Diab-Assaf M, Azar R, Hassan HM, Tayeb S, Abou-El-Ardat K, Damanhouri GA, Qadri I, Abuzenadah A, Chaudhary A, Kumosani T, Niedzwiecki A, Rath M, Yacoub H, Azhar E, Barbour E. Epigallocatechin-3-gallate inhibits tax-dependent activation of nuclear factor kappa B and of matrix metalloproteinase 9 in human T-cell lymphotropic virus-1 positive leukemia cells. Asian Pac J Cancer Prev. 2014;15(3):1219-25.

[18] Huang AC, Cheng HY, Lin TS, Chen WH, Lin JH, Lin JJ, Lu CC, Chiang JH, Hsu SC, Wu PP, Huang YP, Chung JG. Epigallocatechin gallate (EGCG), influences a murine WEHI-3 leukemia model in vivo through enhancing phagocytosis of macrophages and populations of T- and B-cells. In Vivo. 2013 Sep-Oct;27(5):627-34.

[19] Ladas EJ, Kroll DJ, Oberlies NH, Cheng B, Ndao DH, Rheingold SR, Kelly KM. A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL). Cancer. 2010 Jan 15;116(2):506-13.

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