Randomized, Placebo-Controlled Trials of Nutrients that Kill or Prevent Cancer
Colleen Huber, NMD
“The good thing about science
is that it’s true whether or not you believe in it.”
– Neil deGrasse Tyson
Science is a word used in various contexts much more often than it is defined. Science as an idol is sometimes vehemently defended or just as vehemently derided, without regard for what science actually is. Let’s review what constitutes science. Science is the observation of our surroundings, with no or minimal bias, along with the formulation and testing of hypotheses about the nature and function and interactions of our surroundings. That’s it; no ideology, no agenda, no strong emotions.
Strictly objective pursuit of science is usually cumbersome, time-consuming and often expensive. As a practical matter, only a researcher or a student has time to pursue small areas of the vastness of all potential science. The rest of us work with what we know of established fact, or assume of established dogma, and most people don’t usually take time to re-examine and re-test our cherished hypotheses; we simply act on them.
This haste is prevalent in medicine, because the health insurance industry pressures caregivers to hurry through each patient’s visit and care: physical exams, lab tests or imaging, diagnoses and treatment, all within a short period. Therefore, some leaps of faith are necessary. Doctors simply do not have time to test hypotheses with the pressures of the daily workload confronting them. The only expedient way to get through an entire day full of patient appointments is to keep the scrip pad close at hand.
Conventional “standard of care” physicians place their faith in drugs on two things:
(1) the familiar, friendly pharmaceutical representative and the industry behind those drug reps, and
(2) the assumption that at least once in a while the drugs that they sell have been subjected to double-blind or at least placebo-controlled trial.
Most cancer patients, and many doctors as well, would be shocked to learn that chemotherapy drugs have not passed the “gold standard” criteria for drug testing: the double-blind, placebo controlled trial. There are two reasons that these double-blind studies are not done for chemotherapy drugs:
(1) With life-threatening illness, it is considered immoral to have a placebo group, in which no treatment is given, and
(2) The one available study that compared a chemotherapy drug to no treatment at all did not appear flattering for the chemotherapy drug or the industry behind it:
That study found that lung cancer patients treated with the chemotherapy drug Docetaxel survived an average of 7.5 months, whereas those receiving merely supportive care with no chemotherapy or other treatment at all survived an average of 4.6 months. If patients knew of this small difference in survival, would they opt to lose their GI tract function, hair, neurological health, cardiovascular health and other wellbeing?
Worse yet, this study found that the group receiving Docetaxel faced the life-threatening conditions of febrile neutropenia and non-hematologic toxicity.
Was all the misery of chemotherapy worthwhile, not to mention the medical bankruptcy that so many families suffer following chemotherapy – was all of that worthwhile, simply in order to gain 3 more months of life?
On the other hand, many nutrients and herbs have been shown effective and safe against cancer. Let’s examine some of these cancer treatments that do not damage vitality or quality of life, and some double-blind, placebo controlled trials of those substances:
Gastric and esophageal cancer rates in Linxian, China are among the highest in the world. In 1994, a randomized, placebo controlled trial was conducted among 29,584 adults, in a general population study. The experimental group was given one of four nutrient treatments for 5.25 years. The doses were the same or double the US recommended daily allowances of the time. It should be kept in mind that the infamous old “RDA” figures were notoriously low, barely enough to prevent vitamin deficiency.
Even with the very low doses of the supplemented nutrients, it was found that the group having Vitamin A and zinc had 62% less gastric (stomach) cancer than the placebo group.
The group receiving beta-carotene (a small component of all of Vitamin A), Vitamin E and selenium had 42% less esophageal cancer than the placebo cohort. These are statistically significant results, and easily adopted interventions that should have been publicized much more broadly around the world, so that the use of Vitamin A, Vitamin E, and minerals would become more widespread and available.
In another double-blind, placebo-controlled, randomized trial of nutritional supplements, 5141 men were given either a placebo or a single capsule with a very low dose of each of the following sub-optimal forms of generally recognized nutrients:
Vitamin C, alpha-tocopherol (the least effective form of Vitamin E), beta-carotene (one of the least effective forms of Vitamin A), selenium and zinc. They took these daily for 8 years.
There was a statistically significant reduction in the incidence of prostate cancer in the experimental group among the 94% of the men who began the 8 years with a low PSA (<3 micrograms/L). One has to wonder if therapeutic forms and doses of these nutrients had been used, the results may have been even more remarkable.
In another study, which was retrospective, rather than randomized and placebo-controlled, of 37,916 US women, dietary folate and vitamin B-6 was found to reduce the risk of colorectal cancer over the 10 years of the study.
Vitamin D has been shown to be effective against cancer by a number of mechanisms and against a wide range of cancers.
The following randomized, double-blind, placebo-controlled trials show Vitamin D to be effective against the following cancers:
A study that found low levels of vitamin D intake had no effect against cancer mortality in this randomized trial may have come to a different conclusion if therapeutic doses had been used.
Other smaller studies and animal studies have shown benefit of 1,25-D3, the active form of Vitamin D, against the following cancers. Here are a few of those:
Vitamin D metabolites have been shown to have cancer-disrupting effects by several key mechanisms. Vitamin D has been shown to induce differentiation, and apoptosis, to reduce proliferation by effect on signal transduction, to improve intercellular communication by means of gap junction communication preservation, to inhibit angiogenesis,  and to inhibit metastasis.
Very promising research abounds regarding synergistic effect between Vitamin D and Vitamin A. Each of these nutrients used alone induces differentiation – which is a way to normalize the nature and function of cancer cells – in a dose-dependent way. The more consumed, the more differentiation observed, for each of the two vitamins. But this differentiation effect was significantly enhanced when Vitamins A and D were combined  
It may be even more helpful that the synergistic effect of Vitamin A and D together produced permanently ongoing differentiation of cells, even after both nutrients were discontinued, and even though the differentiation achieved by each of those vitamins used alone was reversible.
This synergy of nutrients should of course come as no surprise to those who understand the metabolic pathways in the human body. These pathways, as filtered by our still limited academic understanding of them, make clear that the nutrients are synergistic in their effects on the cells in our bodies. Just as a well-balanced meal is not all one nutrient alone, optimal nutrition is always multi-faceted.
Double-blind, placebo-controlled trials of any therapy are highly risky in cancer patients due to the higher mortality awaiting the group that fares worse. Clinical trials are ended early if it is clear that one group is benefitting much more than the other cohort, in order for both groups to benefit from the more effective treatment. Therefore, I do not encourage or condone further double-blind, placebo-controlled studies of cancer treatments. The consequences of suffering or death in the less fortunate cohort of cancer patients is unacceptable under any circumstances.
However, now that some of these trials have been done, it is very important that we not allow ourselves to forget the knowledge gained from them, because such knowledge may be decisive in saving the lives of cancer patients.
For optimal dosing of the above nutrients in either cancer treatment or cancer prevention, there is no substitute for consulting a licensed naturopathic physician. At our clinic we schedule a lengthy (one hour) initial consult, in order to begin to evaluate the specific nutritional needs of the individual. Other naturopathic physicians whose practices focus on cancer patients may be found at Naturopathic Cancer Society, at www.NatOnco.org, and at Naturopathic Oncology Research Institute, www.NaturopathicStandards.org.
 Shepherd F, Dancey J, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol, 18(10) 2095-2103. May 2000. Pub Med 10811675. https://www.ncbi.nlm.nih.gov/labs/pubmed/10811675-prospective-randomized-trial-of-docetaxel-versus-best-supportive-care-in-patients-with-non-small-cell-lung-cancer-previously-treated-with-platinum-based-chemotherapy/
 Naturopathic Cancer Society. Which cancer are you researching? www.NatOnco.org.
 Taylor P, Li B, et al. Prevention of esophageal cancer: the nutrition intervention trials in Linxian, China. Linxian Nutrition Intervention Trials Study Group. Cancer Res. Apr 1994. 1;54(7 Suppl): 2029s-2031s. https://www.ncbi.nlm.nih.gov/pubmed/8137333
 Greenwald P, Anderson D, et al. Clinical trials of vitamin and mineral supplements for cancer prevention. American Journal of Clinical Nutrition. Jan 2007. 85(1); 3145-3175. http://ajcn.nutrition.org/content/85/1/314S.full#ref-21
 Zhang S, Moore S et al. Folate, vitamin B6, multivitamin supplements and colorectal cancer risk in women. Am J Epidemiol 2006; 163:108-15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1363749/
 Wei M, Garland C, Gorham E, et al. Vitamin D and prevention of colorectal adenoma: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2008 Nov; 17(11): 2958-69. https://www.ncbi.nlm.nih.gov/pubmed/?term=.++Vitamin+D+and+prevention+of+colorectal+adenoma%3A+a+meta-analysis.++Cancer+Epidemiol+Biomarkers+Prev
 Garland C, Gorham E, Mohr F. Vitamin D for cancer prevention: global perspective. Ann Epidem 2009 Jul;19(7):468-83. https://www.ncbi.nlm.nih.gov/pubmed/?term=.++Vitamin+D+for+cancer+prevention%3A+global+perspective.++Ann+Epidem
 Giovannucci E. Vitamin D and cancer incidence in the Harvard cohorts. Ann Epidem. 2009 Feb 19(2): 84-8. https://www.ncbi.nlm.nih.gov/pubmed/?term=Vitamin+D+and+cancer+incidence+in+the+Harvard+cohorts.++Ann+Epidem
 Vahedpoor Z, Jamilian M, et al. Effects of long-term vitamin D supplementation on regression and metabolic status of cervical intraepithelial neoplasia: a randomized, double-blind, placebo-controlled trial. Horm Cancer. Feb 2017. 8(1): 58-67. https://www.ncbi.nlm.nih.gov/pubmed/28050798
 Bostick RM. Effects of supplemental vitamin D and calcium on normal colon tissue and circulating biomarkers of risk for colorectal neoplasms. J Steroid Biochem Mol Biol. Apr 2015, 148:86-95. https://www.ncbi.nlm.nih.gov/pubmed/25597952
 Fedirko V, Bostick R, et al. Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in normal colorectal mucosa: a randomized clinical trial. Cancer Epidemiol Biomarkers Prev. Jan 2010. 19(1): 280-91. https://www.ncbi.nlm.nih.gov/pubmed/20056649
 De Smedt J, Van Kelst S, et al. Vitamin D supplementation in cutaneous malignant melanoma outcome (ViDMe): a randomized controlled trial. BMC Cancer. Aug 2017. 17(1): 562. https://www.ncbi.nlm.nih.gov/pubmed/28835228
 Jarrard D, Konety B, et al. Phase IIa, randomized placebo-controlled trial of single high dose cholecalciferol (vitamin D3) and daily genistein (G-2535) versus double placebo in men with early stage prostate cancer undergoing prostatectomy. Am J Clin Exp Urol. Sept 2016. 20;4(2): 17-27. https://www.ncbi.nlm.nih.gov/pubmed/27766277.
 Schumann, S, Ewigman B. Double-dose vitamin D lowers cancer risk in women over 55. J Fam Pract. Nov 2007. 56(11): 907-910. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294452/
 Lappe J, Travers-Gustafson D. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. Jun 2007. 85(6):1586-91. https://www.ncbi.nlm.nih.gov/pubmed/17556697
 Brunner R, Wactawski-Wende J, et al. The effect of calcium plus vitamin D on risk for invasive cancer: results of the Women’s Health Initiative (WHI) calcium plus vitamin D randomized clinical trial. Nutr Cancer. 2011. 63(6): 827-41. https://www.ncbi.nlm.nih.gov/pubmed/21774589
 Li M, Li L, et al. 1,25-dihydroxyvitamin D3 suppresses gastric cancer cell growth through VDR- and mutant p53-mediated induction of p21. Life Sci. Jun 2017. 179: 88-97. https://www.ncbi.nlm.nih.gov/pubmed/?term=1%2C25-dihydroxyvitamin+D3+suppresses+gastric+cancer+cell+growth+through+VDR-+and+mutant+p53-mediated+induction+of+p21.++Life+Sci
 Saez S, Falette N, et al. 1,25(OH)2D3 modulation of mammary tumor cell growth in vitro and in vivo. William L. McGuire Memorial Symposium. Breast Cancer Res Treat. 1993. 27(1-2):69-81. https://www.ncbi.nlm.nih.gov/pubmed/8260731
 Shen M, Yen A. Nicotinamide cooperates with retinoic acid and 1,25 dihydroxyvitamin D(3) to regulate cell differentiation and cell cycle arrest of human myeloblastic leukemia cells. Oncology 2009; 76(2): 91-100. https://www.ncbi.nlm.nih.gov/pubmed/?term=Nicotinamide+cooperates+with+retinoic+acid+and+1%2C25+dihydroxyvitamin+D(3)+to+regulate+cell+differentiation+and+cell+cycle+arrest+of+human+myeloblastic+leukemia+cells.++Oncology
 Kizildag S, Ates H. Treatment of K562 cells with 1,25 dihydroxyvitamin D(3) induces distinct alterations in the expression of apoptosis-related genes BCL-2, BAX, BCL(XL) and p21. Ann Hematol. 2009 May 28. (Epub ahead of print.) https://www.ncbi.nlm.nih.gov/pubmed/?term=Treatment+of+K562+cells+with+1%2C25+dihydroxyvitamin+D(3)+induces+distinct+alterations+in+the+expression+of+apoptosis-related+genes+BCL-2%2C+BAX%2C+BCL(XL)+and+p21.++Ann+Hematol.
 Wu W, Zhang X, Zanello L. 1alpha, 25 dihydroxyvitamin D(3) anti-proliferative actions involving vitamin D receptor-mediated activation of MAPK pathways and AP-1/p21 (waf1) upregulation in human osteosarcoma. Cancer Lett. 2007 Aug 28. 254(1): 75-86. https://www.ncbi.nlm.nih.gov/pubmed/?term=MAPK+pathways+and+AP-1%2Fp21+(waf1)+upregulation+in+human+osteosarcoma
 Fujioka T, Suzuki Y, Okamoto T, et al. Prevention of renal cell carcinoma by active vitamin D(3). World J Surg. 2000 Oct; 24(10): 1205-10. https://www.ncbi.nlm.nih.gov/pubmed/?term=.++Prevention+of+renal+cell+carcinoma+by+active+vitamin+D(3).++World+J+Surg
 Bao B, Yao J, Lee Y. 1alpha, 25-dihydroxyvitamin D3 suppresses interleukin-8-mediated prostate cancer cell angiogenesis. Carcinogenesis. 2006 Sep; 27(9): 1883-93. https://www.ncbi.nlm.nih.gov/pubmed/?term=.++1alpha%2C+25-dihydroxyvitamin+D3+suppresses+interleukin-8-mediated+prostate+cancer+cell+angiogenesis.++Carcinogenesis
 Chung I, Han G, Seshadri M, et al. Role of Vitamin D receptor in the antiproliferative effects of calcitriol in tumor-derived endothelial cells and tumor angiogenesis in vivo. Cancer Res. 2009 Feb 1; 69(3):. 967-75. https://www.ncbi.nlm.nih.gov/pubmed/?term=Role+of+Vitamin+D+receptor+in+the+antiproliferative+effects+of+calcitriol+in+tumor-derived+endothelial+cells+and+tumor+angiogenesis+in+vivo.++Cancer+Res
 Yudoh K, Matsuno H, Kimura T. 1alpha, 25-dihydroxyvitamin D3 inhibits in vitro invasiveness through the extracellular matrix and in vivo pulmonary metastasis of mouse melanoma. J Lab Clin Med. 1999 Feb 133(2): 120-8. https://www.ncbi.nlm.nih.gov/pubmed/?term=.++1alpha%2C+25-dihydroxyvitamin+D3+inhibits+in+vitro+invasiveness+through+the+extracellular+matrix+and+in+vivo+pulmonary+metastasis+of+mouse+melanoma.++J+Lab+Clin+Med
 Defacue H, Commes T. Synergistic differentiation of U937 cells by all-trans retinoic acid and 1 alpha, 25-dihydroxyvitamin D3 is associated with the expression of retinoid X receptor alpha. Biochem Biophys Res Commun. Aug 1994. 203(1):272-80. https://www.ncbi.nlm.nih.gov/pubmed/8074666
 Blutt S, Allegretto E. 1,25-dihydroxyvitamin D3 and 9-cis-retinoic acid act synergistically to inhibit the growth of LNCaP prostate cells and cause accumulation of cells in G1. Endocrinology. Apr 1997. 138(4):1491-7. https://www.ncbi.nlm.nih.gov/pubmed/9075707
 Verstuyf A, Mathieu C. Differentiation induction of human leukemia cells (HL60) by a combination of 1,25-dihydroxyitamin D3 and retinoic acid (all trans or 9-cis). J Steroid Biochem Mol Biol. Jun 1995. 53(1-6):431-41. https://www.ncbi.nlm.nih.gov/pubmed/7626492