How Nutraceutical Research Should be Done: Lycopene for Osteosarcoma in Dogs

Proponents of nutraceuticals, nutritional supplements thought to have therapeutic or preventative effects, often promote the use of such products despite little or no legitimate evidence to suggest they will be safe or helpful. When skeptics challenge these unsupported claims, they are frequently accused of being opposed to nutraceuticals or supplements per se regardless of the evidence, or of not wanting such things to be studies for fear that “free” remedies (not that any of these aren’t making a buck for somebody) would crowd the drug companies’ territory.

These are empty strawmen, of course, but it is true that I often find myself criticizing the inadequate evidence given to support using such products, or the poor quality of the research cited. I am pleased, then to be able to cite an example of how good quality, science-based research into the potential benefits of nutritional supplements should be done.

Wakshlag JJ, Balkman CE. Effects of lycopene on proliferation and death of canine osteosarcoma cells. American Journal of Veterinary Research 2010;71(11):1362-70.

The authors begin by pointing out that despite the fact “there is little evidence that single dietary carotenoids are beneficial,… carotenoid-rich nutraceuticals are available as over-the-counter products in both the veterinary and human market, and the incidence of nutraceutical use in pets with cancer is approximately 40%; therefore, understanding the functional importance of such carotenoids is extremely important, particularly when other chemotherapuetic agents are used.” The market, and those making money selling such supplements, are as usual well ahead of the research. However, there is some evidence of possible benefit in humans, so preliminary, pre-clinical studies to see if there might be benefit in dogs is appropriate.

One level of such research is showing that the substance can be taken orally by dogs and reach meaningful levels in the blood. One of the weaknesses in the preclinical data concerning glucosamine was the uncertainty over this point, which ought to be established before resources are wasted on clinical trials. According to the authors of this paper, such studies have been done and do show potentially meaningful blood and tissue levels of lycopene can be achieved by oral administration, so there is enough plausibility to justify further research.

The current study was intended investigate whether lycopene has an effect on canine osteosarcoma cells in vitro (that is, outside of the body), and also critically whether or not the substance appears to interfere with the effect of a common chemotherapy drug used against this cancer. As I’ve mentioned before, Vitamin C has been shown to potentially reduce the effectiveness of chemotherapy, and since many of the supplements now touted for cancer treatment are anti-oxidants, there is a real risk that they will interfere with the oxidative mechanisms by which established cancer treatments work, yielding a net loss for patients. In this case, the lycopene did seem to have a significant effect inhibiting the growth of the cancer cells, and it did not seem to enhance nor impede the effect of the chemotherapy agent tested.

Now, in vitro studies are important in establishing potential mechanisms by which drugs might have benefits, and in identifying potential sources of harmful effects. But the test tube is not the body, and they are not very reliable guides to the chances for real-world benefits in actual patients. After all, bleach kills cancer cells in a test tube, but it wouldn’t make a very good drug for cancer patients. The overwhelming majority of substances that show promise in the lab turn out not to be useful in actual patients, which is part of why development of effective medicines is so expensive.

Proponents of herbs and dietary supplements often try to support their claims with such laboratory research without recognizing the important limitations of such studies. To their credit, the authors of this paper not only did excellent research, but they recognized the limits to what their research means.

…regardless of the similar biological nature of osteosarcoma cells clinically, their reactivity to antineoplastic agents in vitro and in soft agar assays can differ dramatically from their in vivo reactivity, and further investigation into the antiproliferative effects of lycopene in vivo would be needed to prove the potential efficacy of such treatment.

Lycopene concentrations in tissue range from 100nM to 5?M, which makes tissue distribution highly variable but promising depending on tumor location. However, without knowing tissue concentrations of lycopene in tumors and having knowledge about cellular distribution, any suggestions of physiologic relevance are merely speculative.

The fact that physiologic doses of lycopene may be achievable in dogs, in conjunction with the efficacy of the in vitro study reported here, warrants future investigation into the use of lycopene as a chemopreventative, and possibly even as a chemotherapeutic, agent in the treatment of osteosarcoma in dogs.

It is likely that this study will eventually be cited in support of recommending lycopene for dogs with osteosarcoma. Regardless of whether or not the substance eventually turns out to be useful for treating this cancer, recommending it on the basis of this paper would be inappropriate. The authors themselves have the humility to understand this and not to extend the significance of their results beyond appropriate bounds. I wholeheartedly support such research, and I agree that the plausibility suggested by this report justifies further study.

While it is painful to see patients in my practice suffering from osteosarcoma, and to not have therapies as safe and effective as I would like to offer them, I understand, as do the authors of this excellent study, that I am doing my patients no service by recommending supplements that have yet to demonstrate they are safe and effective unless I am prepared to do so within the context of a research project appropriately designed to find this out. False hope and uncontrolled, haphazard use of nutraceuticals is not good for our patients, and if we really want to help them we must have the humility and discipline to accept and disclose the limitations in our knowledge.

I hope the authors of this study continue to pursue this promising line of research, and if at the end of the line is a therapy of real benefit I will be joyful. And if the end of the line is one of the far more common dead ends, I am confident the authors will see and accept that and move on to investigate other promising avenues. Such careful and honest work is why science-based medicine is so successful.

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