Liz Sutherland: today I have the pleasure of interviewing Dr. Donald Abrams, who will be presenting at the Restorative Medicine Conference in San Diego. Dr. Abrams is currently an integrative oncologist at the UCSF Osher Center for Integrative Medicine, and professor of clinical medicine at the University of California at San Francisco. Dr. Abrams please tell us some of the highlights of your background and how you came to the practice of integrative oncology.
Donald Abrams: At the beginning of my training to be an oncologist, AIDS suddenly came out of the blue. We didn't know what it was or what to do about it, and so I became a champion of alternative therapies, even when there was no conventional therapy to be alternative to. I wrote the chapters in all the AIDS textbooks on complementary and alternative therapies in HIV. In 1992, somebody challenged me to study cannabis as a treatment for the AIDS wasting syndrome. I went to college in the 60s so I fought the government and ultimately won and got access to marijuana and money to do research, which gave me a strong appreciation of the power of plants as medicine.
A little later I met Andrew Weil At the Telluride Mushroom Festival, and I signed up for his program in integrative medicine at the University of Arizona. It changed my life. When I finished, I decided that after 25 years I was done with HIV AIDS research. I wanted to do integrative oncology, working with people living with and beyond cancer, and helping them to integrate these other modalities into their conventional care." In 2005 I went to our Osher Center for Integrative Medicine and began my integrative oncology practice there and subsequently at San Francisco General Hospital. At the Osher Center I treat people living with cancer. I tell them that cancer is like a weed and someone else is taking care of that weed, so it's my job to work with the garden and make the soil as inhospitable as possible to growth and spread of the weed. I do that by looking to see what they eat and what supplements they take.
LS: I noticed in the 2018 American Institute for Cancer Research Report they recommend against the use of supplements for cancer prevention. Do you have any thoughts about that?
DA: That’s because most of the studies looking at individual vitamins, particularly for decreasing the risk of cancer, have failed to demonstrate a benefit. In fact, most of them have demonstrated a detriment. Let's start with A or beta-carotene. The first study, the CARET Study, looked at 30,000 men who smoked tobacco to see if vitamin A in the form of a beta-carotene supplement, vitamin E, both, or neither could decrease the risk of lung cancer. This study was stopped early because the people getting beta-carotene supplementation actually had an increased risk of lung cancer. It was confirmed in two other large 30,000 plus studies. The CARET Study did suggest that men receiving Vitamin D supplementation may have had a decreased risk of prostate cancer. That led to the SELECT Study, which compared vitamin E, selenium, both, or neither as an intervention to reduce the risk of prostate cancer in older men. That study was also stopped early because it appeared that vitamin E increased the risk of prostate cancer. A more prolonged follow up confirmed that both vitamin E and selenium in men who already had adequate selenium levels increased the risk of prostate cancer. However, as you know, vitamin E in nature exists in eight different isoforms: alpha, beta, gamma, and delta tocopherol; and alpha, beta, gamma, and delta tocotrienol. Most multivitamins, including the vitamin E in this study, use only d-alpha tocopherol. Critics said, "If you're giving people 400 times their daily requirement of d-alpha, they're not going to absorb the gamma tocotrienol, which may be the anticancer agent."
This was a concern about the studies, but two studies of fat soluble vitamins showed a detriment. What about water soluble vitamins? A study was done in elderly adults to see if B vitamins could decrease the progression of their heart disease. They were randomized to receive vitamin B6, folic acid and B12, all three, or placebo. There were about 2,000 people in each group followed for three and a half years. At the end of the study, patients randomized to B12 and folic acid had increased rates of cancer, death from cancer, and death from all-cause mortality. I think the bad actor there is folic acid, which is synthetic folate. It’s been shown to increase prostate cancer risk. I think folic acid allows pre-malignant cells to continue to divide to the point where the malignant switch turns on and they become cancer.
I'm a big proponent of vitamin D. There's significant epidemiologic data to suggest that people with low vitamin D levels are at greater risk for cancer, and people with cancer whose vitamin D levels are low, don't do as well as people whose vitamin D levels are normal. The only blood test I get on patients I see in my integrative oncology practice is a 25-hydroxy vitamin D level. I like my patients to be between 40 and 50 ng/ml. However, the VITAL study, which was recently published in the New England Journal, put a slight dampener on my enthusiasm. This study looked at 20,000 older adults randomized to receive vitamin D, Omega-3, both, or neither. One paper has been published on Omega-3 and one on the vitamin D outcome. Neither of them showed these supplements improved the primary endpoint, which was death from cancer or cardiovascular disease. I think the Omega-3s did decrease the number of myocardial infarctions. And the vitamin D decreased death from some cancers but not all cancers. That being said, I still like vitamin D and Omega-3s. I use them to prevent subsequent cancer because all the patients I see already have cancer. We think that cruciferous vegetables and green tea decrease the risk of cancer, again from large epidemiologic studies, but we're not saying, "Take sulforaphane capsules or an ECGC capsule." We're saying, "Eat the foods and obtain the benefit from your nutrition."
LS: All of this points to the complexity of doing nutritional research. I'm sure you appreciate it’s not realistic to just start with day one of a trial as being all that matters about a person’s nutritional history.
DA: Right. I always say that.
LS: Have the negative associations of the research on using supplements for cancer prevention made you more circumspect about prescribing supplements or botanical medicines for your patients?
DA: I don't prescribe because I'm not their primary oncologist. I usually write a prescription for vitamin D for my patients at San Francisco General. I also think that calcium is an important supplement. I ask people to decrease or eliminate dairy, and dairy is the major source of calcium in the diet. Calcium and magnesium may both help decrease the risk of colon cancer. Calcium may increase the risk of prostate cancer, so I don't recommend huge doses for men in that age group. Generally I recommend calcium, magnesium, vitamin D (to bring levels to 40 or 50), and Omega-3s. I like turmeric as an anti-inflammatory and perhaps having some anticancer activity. I'm also a big fan of medicinal mushrooms. The 1,3-beta glucan wall of the mushroom resembles a bacterial cell wall, so our body thinks it's being infected by bacteria and mounts a nonspecific immune response, which may be useful in fighting cancer. When patients have had chemo, which is a pretty potent antibiotic, I also suggest they take a probiotic.
LS: Is there anything you recommend your patients either avoid or supplement prior to undergoing chemotherapy, radiation, or immunotherapy?
DA: Regarding immunotherapies, there is no evidence that medicinal mushrooms would be contraindicated, but I tell my patients not to take them when they're getting immunotherapy because they're both immune enhancers. If immunotherapy works, it really has potential to be quite effective, and so I wouldn't want the mushrooms to interfere. There's also evidence that the microbiome is very important in response to these PDL 1 inhibitor immunotherapies, and that patients who take probiotic capsules don't generally do as well as people who don't. I ask patients on immunotherapy to forgo both their probiotic capsules and medicinal mushrooms.
I generally allow people to eat an antioxidant-rich diet throughout their cancer treatment, but recommend they not take supplemental antioxidants when they're getting radiation, or if they're getting chemo that is working through generating free radicals. For patients having surgery, I often recommend they take vitamin C and zinc in the perioperative period to increase wound healing, but to stop the rest of the time. I see a lot of people who take melatonin, which some people say is an antioxidant, but most of the integrative oncologists I know aren't fearful of patients taking melatonin while they're getting radiation or chemotherapy. I use Coenzyme Q 10 for energy or especially in people who are on statins because statins deplete coenzyme Q 10. I also use it for women who have had radiation to their left breast because it's cardio-protective. If the goal of treatment is palliation not cure, and the patient really wants to take vitamin C or whatever while they're getting chemo, I'm not about to argue with them.
LS: You'll be presenting on cannabis at the conference. Can you give us a preview regarding what you recommend cannabis for, in what form, and how you recommend dosing it?
DA: We cannot prescribe cannabis, we can only recommend it. I think cannabis is a very useful anti-emetic. We have dronabinol and nabilone, which are delta-9 tetrahydrocannabinols, the single most psychoactive moieties of cannabis. These are licensed and available for treatment of chemotherapy-induced nausea and vomiting based on studies. If the single most active ingredient is effective, then you’d think the plant would be as well. Although there are not a lot of clinical studies in the literature to support that, my experience over 36 years as an oncologist tells me that cannabis is an effective anti-emetic. It's also the only anti-emetic that increases appetite.
Our endogenous cannabinoid system probably helps modulate our response to pain. The largest evidence base for this in the literature is for neuropathic pain, not necessarily chemo-induced neuropathy, but HIV neuropathy and even a small study in diabetic neuropathy. In animal models, laboratory cannabinoids seem to not only treat but also prevent chemotherapy-induced neuropathy caused by the vinca alkaloids, taxanes, and platinums, which are the three main classes of chemotherapy agents. In addition, insomnia seems to be something that both THC and CBD may be able to address. Some people get increased anxiety and in fact paranoia from cannabis. Other people appreciate the mellow, chill effect. This probably depends on the strain and maybe even pharmacogenomics. Those are most of the indications that I recommend cannabis for.
Some patients think that cannabis is going to cure their cancer. There is no evidence that cannabis or even highly concentrated oils of CBD or THC have any effect on malignant disease in humans. Patients sometimes wait a few months to see me, and they're treating a potentially curable cancer with these highly concentrated oils hoping that I'm going to tell them it was a good idea when in fact now they might have metastatic disease. This upsets me a great deal.
LS: Are you allowed within your recommendations to discuss how to dose and what form of cannabis would be more effective?
DA: I am but I don't. First of all, I don't know what the dispensaries carry. Next, the only evidence in the medical literature comes from NIDA marijuana. NIDA is the only legal source of cannabis for research in the country. My as yet unpublished study in sickle cell disease is the first study that's going to investigate a blend of NIDA cannabis that contains CBD as well as THC. The literature is not very helpful in giving me evidence from which to make recommendations.
I do know from my own studies that with inhaled cannabis either vaporized or smoked, plasma concentration of THC peaks in two and a half minutes and then dissipates quite rapidly over the next 30 minutes. If you take cannabis by mouth as an edible product, peak plasma concentration is much lower and occurs in two and a half hours.
When delta-9 THC is taken by mouth, however, it goes through the liver and is converted into an even more psychoactive 11-hydroxy metabolite via first-pass metabolism. The terminal half-life when taken by mouth is 20 to 30 hours. I tell my patients, if you want better control over the onset, depth, and duration of effect, inhalation is probably better than ingestion. Sublingual tinctures and oils seem to provide rapid absorption, so they might prove to be a hybrid in the pharmacokinetics between inhaled and ingested. But again, I don't know what the dispensary has. Even 23 years into this here in California, I tell my patients, go to the dispensary, tell them what it is we're trying to treat and ask them what they think works best because they are the ones on the front line and they have a lot more experience with their products than I do.
LS: Thank you so much, Dr. Abrams. We look forward to hearing you present in San Diego.