Apr 8, 2016

Can concentrating foods into supplements enhance their anti-cancer effects?

supplementsIf certain foods have anti-cancer effects, then it is not unreasonable to hypothesise that concentrating them into a pill may be a good way to supplement individuals with poor diets or further enhance the benefits in those whose diets are already adequate.

People living with and beyond cancer are certainly attracted to the potential health benefits of food supplements, as over 65% report regular intake1,2.

There are two main categories of supplements commercially available: the first involves chemicals extracted from food, or made synthetically, such as vitamins and minerals; the second involves purifying and concentrating whole foods.

Vitamins and mineral supplements

The majority of studies to date have evaluated extracted chemicals, such as vitamins and minerals. Some have shown a benefit:

  • A recent meta-analysis of studies reported that women who took supplements providing an average daily intake of vitamin C over 100mg had a reduced risk of breast cancer relapse3.
  • The SU.VI.MAX study randomised French adults to a single daily capsule of ascorbic acid, vitamin E, beta carotene, selenium and zinc, or a placebo, and found no reduction in mortality or cancer-specific mortality overall4, although a further analysis in men found a reduction in the risk of prostate cancer. The authors postulated that this difference between the sexes was related to French men having a lower baseline micro-nutrient status5.
  • A major trial of selenium and vitamin supplements in a poor region of China, demonstrated reduced risks of oesophageal cancer; at the time, this population was known to have widespread micro-nutrient deficiencies6.

Unfortunately, most other studies of vitamin, minerals and other extracted nutrients have shown no benefit, or have actually shown an increased risk of cancer:

  • The CARET study found that beta carotene and retinol increased the risk of lung cancer7. The Health Professionals Follow-up study (HPFS), which followed the lifestyle habits of 51,529 male professionals for over 15 years, found that men who took very high doses of zinc (>100mg/day), or took it for long durations were more than twice as likely to develop advanced prostate cancer compared with controls8.
  • The randomised SELECT study demonstrated an increased prostate cancer incidence with vitamin E and selenium supplementation9.
  • A further analysis of the HPFS found that of the 4,459 men who had developed prostate cancer, those who took selenium supplementation of ≥140 μg/d after diagnosis were associated with a 2.60-fold greater risk of prostate cancer mortality10.
  • The negative effects of vitamin E and beta carotene were once again demonstrated in the ATBC study, which found them to increase lung cancer risk, although subsequent analysis showed that men with pre-intervention low plasma levels of beta-carotene had a lower prostate cancer risk following supplementation, and that those with high levels had a higher risk, particularly in smokers11. This u-shaped distribution of risk was also observed in the EPIC study where those with folate-deficient diets and those with the highest intake both had a higher risk of cancer12. These data have prompted organisations, such as the National Cancer Institute, to issue statements stating that long term vitamin and mineral supplements should ideally be given to correct a known deficiency13, which is rarely routinely detected unless individuals have self-funded micro-nutrient analysis (http://www.cancernet.co.uk/).

Whole-food supplements

More recently, academic attention has turned towards the evaluation of fruitconcentrated whole-food supplements, particularly foods rich in polyphenols and other phytochemicals such as herbs, spices, green vegetables, teas and colourful fruits, which have appeared to be beneficial in environmental cohort studies.

Despite some initial encouragement from smaller evaluations, studies of extracted lycopene or genistein given on their own in more scientifically robust analyses have not demonstrate a benefit for either prostate cancer or benign prostatic hypertrophy,14,15,16 and there were no links with the reduction in the risks of breast cancer with regular intake5.

Of more concern, a randomised study from Memorial Sloan Kettering reported that serum taken from women who take very high-dose soy supplementation (25.8 g twice a day) added to laboratory tumour cells caused them to proliferate faster (increased K67 expression) and overexpress the tumourigenic growth factor receptor FGFR217. This supports the notion that phytoestrogen foods are healthy, but concentrating them into strong supplements is not recommended.

On the other hand, no study of non-phytoestrogenic foods supplements have shown any detrimental effects on cancer outcomes and some have beneficially influenced progression rates:

  • A study carried out at John Hopkins involving pomegranate seed extract, found that men taking the supplements had a reduction in prostate-specific antigen (PSA) progression rate18.
  • A study conducted at the Mayo Clinic found that green tea concentrate decreased the abnormal white cell count in 30% of patients with chronic leukaemia, and a small study from Louisiana University reported that green tea concentrate significantly reduced levels of several cancer-promoting growth factors as well as PSA levels in participants19.
  • In the Vitamins and Lifestyle (VITAL) cohort study, a regular intake of grapeseed extract was shown to be linked with a lower risk of prostate cancer16, and another small randomised study found that a dietary supplement containing isoflavones, plus other phytochemicals and anti-oxidants delayed PSA progression20. Interestingly one of the most popular supplements, Saw Palmetto, despite an effect in early small studies, showed no benefit for prostate cancer or benign prostatic hypertrophy in the largest randomised evaluation21. Likewise, another popular supplement, lycopene, despite similar suggestions from smaller non-randomised trials14,15, demonstrated no benefits in a more robust evaluation.
  • So far, the largest trial analysing phytochemical-rich food extracts was the National Cancer Research Network-adopted Pomi-T study22. This study combined four different food types (pomegranate, green tea, broccoli and turmeric) in order to provide a wide spectrum of synergistically acting nutrients, while at the same time avoiding over-consumption of one particular phytochemical. It involved two hundred men, with localised prostate cancer managed with active surveillance or watchful waiting experiencing a PSA relapse, following initial radical interventions. The results, presented as an oral presentation at the American Society of Clinical Oncology (ASCO) conference showed a statistically significant 63% reduction in the median PSA progression rate compared to placebo in both men on active surveillance and experiencing a PSA relapse post-treatment. A further analysis of MRI images, demonstrated the cancer size and growth patterns correlated with PSA changes, excluding the possibility that this was just a PSA rather than tumour effect22. It was well tolerated, apart from some mild loosening of the bowels in 10% of men, and there was no effect on testosterone levels. At 6 months, significantly more men opted to remain on surveillance rather than proceeding to expensive radiotherapy, surgery or medical castration, which can cause unpleasant effects such as depression, hot flushes, weight gain, osteoporosis and erectile dysfunction22.

A number of other randomised trials involving whole-food phytochemical-rich supplements have demonstrated benefits for some of the distressing symptoms common after cancer treatments, such as fatigue23 and urinary infections24. There are currently over ten on-going studies registered with the National Institute of Health. In the UK, the Institute of Preventative Medicine has plans to include the Pomi-T supplement into the next national prostate cancer prevention study. This study will be recruiting men with a higher genetic risk of prostate cancer identified in the national RAPPER study, co-ordinated by the Institute of Cancer Research. Further trials are being designed involving men with prostate cancer already on androgen-deprivation therapy and individuals with skin, colorectal and bladder cancer. In the meantime, a trial is passing through the regulatory process to investigate whether the natural anti-inflammatory properties of these ingredients could help joint pains after breast cancer.

Sources:

  1. Bauer CM, Johnson EK, Beebe-Dimmer JL, et al. Prevalence and correlates of vitamin and supplement usage among men with a family history of prostate cancer. Integrative Cancer Therapies 2012;11(2): 83-89.
  2. Uzzo RG, Brown JG, Horwitz EM, et al. Prevalence and patterns of self-initiated nutritional supplementation in men at high risk of prostate cancer. British Journal of Urology International 2004;93(7): 955-960.
  3. Harris HR, Orsini N and Wolk A. Vitamin C and survival among women with breast cancer: a metanalysis. European Journal of Cancer 2014;50(7): 1223-1231.
  4. Hercberg S Galan P, Preziosi P, et al. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Archives of Internal Medicine 2004;164(21): 2335-2342.
  5. Meyer F, Galan P, Douville P, et al. Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial. National Library of Medicine. International Journal of Cancer 2005;116(2): 182-186.
  6. Blot WJ, Li JY, Taylor PR, et al. Nutritional intervention trials in Linxian China: supplementation with specific vitamin/mineral combinations, cancer incidence and disease specific mortality in the general population. Journal of the National Cancer Institute 1993;85: 1483-1491.
  7. Omenn GS, Goodman GE, Thornquist MD, et al. Risk factors for lung cancer and for intervention effects in CARET, the beta-carotene in retinol efficacy trial. Journal of the National Cancer Institute 1996;88: 1550-1559.
  8. Leitzmann MF, Stampfer MJ, Wu K, et al. Zinc supplementation and the risks of prostate cancer. Journal of the National Cancer Institute 2003;95(13): 1004-1007.
  9. Klein EA, Thompson IM, Tangen CM, et al. Vitamin E and the risk of prostate cancer. The selenium and vitamin E cancer prevention trial (SELECT). Journal of the American Medical Association 2011;306(14): 1549-1556.
  10. Kenfield SA, Van Blarigan EL, DuPre N, et al. Selenium supplementation and prostate cancer mortality. Journal of the National Cancer Institute 2014;107(1): 360.
  11. Heinonen O, Albanes D, Virtamo J, et al. Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. Journal of the National Cancer Institute 1998;90: 440-446.
  12. Chuang S. A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. European Journal of Cancer 2011;47: 1808-1816.
  13. Greenwald P, Milner JA, Anderson DE, et al. Micronutrients in cancer chemoprevention. Cancer and Metastasis Review 2002;21(3-4): 217-230.
  14. Clark PE, Hall MC, Borden LS, et al. Phase I-II prospective dose-escalating trial of lycopene in patients with biochemical relapse of prostate cancer. Urology 2006;67(6): 1257-1261.
  15. Clark PE, Rimm EB, Liu Y, et al. A prospective study of tomato products, lycopene and prostate cancer risk. Journal of the National Cancer Institute 2002;94: 391-398.
  16. Brasky TM, Kristal AR and Navarro SL. Specialty supplements and prostate cancer risk in the VITamins and Lifestyle (VITAL) cohort. Nutrition and Cancer 2011;63(4): 573-582.
  17. Shike M, Doane A, Russo L, et al. The Effects of Soy Supplementation on Gene Expression in Breast Cancer: A Randomized Placebo-Controlled Study. Journal of the National Cancer Institute 2014;106(9).
  18. Carducci MA, Paller CJ, Wozniak P, et al. A phase II study of pomegranate extract for men with rising PSA. Journal of Clinical Oncology 2011;29(7): 11-19.
  19. Shanafelt TD, Call TG, Zent CS, et al. Phase I trial of daily oral polyphenon E (green tea extract) in patients with asymptomatic stage 0-II chronic lymphatic leukaemia. Journal of Clinical Oncology 2009;27(23): 3808–3814.
  20. Schröder FH, Roobol MJ, Boevé ER, et al. Randomized, double-blind, placebo-controlled crossover study in men with prostate cancer and rising PSA: effectiveness of a dietary supplement. European Urology 2005;48(6): 922-930.
  21. Bent S, Kane C, Shinohara K, et al. Saw Palmetto for Benign Prostatic Hyperplasia. New England Journal of Medicine 2006;354(6): 557-566.
  22. Thomas R, Williams M, Bellamy P, et al A double blind, placebo controlled randomised trial (RCT) evaluating the effect of a polyphenol rich whole food supplement on PSA progression in men with prostate cancer – The UK National Cancer Research Network (NCRN) Pomi-T study. Prostate Cancer and Prostatic Diseases 2014;17: 180–186.
  23. Barton DL, Liu H, Dakhil SR, et al. Wisconsin Ginseng (Panax quinquefolius) to improve cancer-related fatigue: a randomized, double-blind trial. Journal of the National Cancer Institute 2013;105(16): 1230-1238.
  24. Bonetta A and Di Pierro F. Enteric coated highly standardized cranberry extract reduces risk of UTI’s and urinary symptoms during and after radiotherapy for prostate cancer. Cancer Management and Research 2012;4: 281-286.

 

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