Antioxidants and Chemotherapy

A listserv friend recently wrote a post about a study titled Impact of antioxidant supplementation on chemotherapeutic efficacy: A systematic review of the evidence from randomized controlled trials, published in Cancer Treatment Reviews in January 2007. With the help of an Italian friend (grazie mille!), I managed to gain access to the full study, not just the abstract (which is available at: http://tinyurl.com/24xm2u). It is estimated that between 13 and 87 % of all cancer patients take antioxidant supplements. Significant numbers. Yet many MM patients have told me that their doctors warned them, sometimes quite strongly!, against taking any supplements while doing chemotherapy, based on the myth that supplements could interfere with and even diminish treatment efficacy. Well, perhaps this 2007 study will debunk the myth once and for all.

This group of researchers went through electronic databases and looked at the randomized, controlled clinical trials that reported survival and/or tumor response 19 trials met the inclusion criteria. Antioxidants evaluated were: glutathione (7), melatonin (4), vitamin A (2), an antioxidant mixture (2), vitamin C (1), N-acetylcysteine (1), vitamin E (1) and ellagic acid (1). Subjects of most studies had advanced or relapsed disease. A total of 1554 patients were evaluated. Most of the 845 trials were excluded for a variety of reasons–because they were not controlled trials, because antioxidants were not given together with chemotherapy, etc.

An aside: since ellagic acid is on my June list, I was interested to read that prostate cancer patients taking ellagic acid had significantly decreased neutropenia over patients taking a placebo (33 versus 75 %). Those patients also lived longer and had a better response to treatment. Another interesting bit of news is that all studies reported similar or less neurotoxicity in the antioxidant group than the control group.

The study concludes that patients taking antioxidants during chemotherapy had increased survival, increased tumour responses and fewer toxic side effects. The researchers hope that their data will pave the way to larger studies on the concurrent use of antioxidants with chemotherapy. However, even though this study examined only a small sample of clinical trials, I believe its findings are significant enough to make dubious doctors change their minds on supplements. About time.

Honokiol and MM

When we moved into our house about six years ago, the most imposing feature in our small front yard was (is!) a huge magnolia tree that was planted, I was told, about 45 years ago (yes, it’s as old as I am, what an odd coincidence, huh?) by the previous owners and never pruned. I used to think this tree (see photo) was such a nuisance because it is so messy. Its fallen leaves suffocate my herb plants and flower beds. However, recently I have come to look at it as a symbol of my quest to find alternative treatments for my MM. Why? Because magnolia trees contain a very important active component called honokiol, extracted from its bark and seed cones. Honokiol has been used for about two thousand years in China and Japan to treat a variety of disorders €”anxiety, nausea, fever, coughs, headaches, digestive problems, etc.

In 2005, a study carried out by a group of researchers at the Dana Farber/Harvard Medical School and published in “Blood” revealed that honokiol induces apoptosis in B-cell chronic lymphocytic leukaemia cells (http://tinyurl.com/3dqfdm), without killing normal B-cells (good news!). Another bit of good news is that low doses of honokiol increase the cytotoxicity potential of three chemo drugs used in B-CLL. Detail of my magnolia tree

A few months later, a study on honokiol and MM was published in Blood (http://tinyurl.com/2kgdoh). A group of researchers found that honokiol has antioxidant, antifungal and antibacterial properties (sound familiar? Yep, curcumin!). Their most significant discovery, however, was that honokiol inhibits growth and induces apoptosis of MM cells. Honokiol, or HNK, was also found to enhance the anti-MM properties of bortezomib (Velcade). The growth of MM cells taken from patients with relapsed/refractory MM was also greatly reduced by honokiol. And I would like to underline that normal cells treated with honokiol were not negatively affected. More similarities with curcumin, which affects only cancer cells. The study concludes that HNK induces apoptosis via caspase-dependent and -independent pathways in MM cells. It induces cell death in drug-resistant MM cells and overcomes the growth-promoting activities of IL-6, IGF-1, and BMSCs; its antiangiogenesis activity further supports its anti-MM potential in the BM milieu. These results suggest that HNK, used either alone or in combination with other drugs, represents a promising novel targeted approach to overcome drug resistance and improve patient outcome in MM.

A 2006 study (http://tinyurl.com/3xyxcc) reports that the NF-kB and NF-kB-regulated gene expression inhibited by honokiol enhances apoptosis and suppresses osteoclastogenesis and invasion. Another osteoclastogenesis inhibitor. Well, well. However, how do we figure out dosages and how can we be sure that what we buy is absolutely pure and safe? Good question. And what about side effects (apart from possible drowsiness, which I did read about) with high doses of honokiol? Another good question. There are currently no clinical trials testing honokiol, which I think is a shame, given its potential in vitro and in vivo. Perhaps I should just begin chewing on the bark from my magnolia tree. 😉

A selection of studies on honokiol and:

angiogenesis (http://tinyurl.com/2f4y9t);

breast cancer (http://tinyurl.com/2a29jz);

prostate cancer (http://tinyurl.com/ytjamb);

neurodegenerative diseases (http://tinyurl.com/yus8qv);

colorectal carcinoma, (http://tinyurl.com/2eqmxs);

acute promyelocytic leukaemia (http://tinyurl.com/yrk48x);

cerebral infarction (http://tinyurl.com/yo622p);

antimicrobial activity (http://tinyurl.com/2z35o8);

myocardial ischemia (http://tinyurl.com/yotpdw);

hematologic malignancies (http://tinyurl.com/3e3dj8);

acetylcholine levels (Alzheimer’s disease) (http://tinyurl.com/36y5a3)

Friday Humour

It’s Friday, and I feel happy today: the weekend is around the corner, plus it’s another glorious sunny day in Florence! So, after writing about crazed osteoclasts yesterday, I am going for a bit of humour today, following my own advice to laugh as much as possible in order to stimulate my immune system and natural killer cells. Are you afraid of flying? Well, I wasn’t, until I reached my early 30s when for some unknown reason I began to develop a bit of flying anxiety. Hmmm, well, on second thought, it could have started when I landed in Toronto once during a snowstorm. That was NOT fun. At any rate, what follows is a collection of (apparently!) REAL in-flight announcements. I saved the best for last

Heard on a Southwest Airline flight. “Ladies and gentlemen, if you wish to smoke, the smoking section on this airplane is on the wing and if you can light ’em, you can smoke ’em.”

“Thank you for flying Delta Business Express. We hope you enjoyed giving us the business as much as we enjoyed taking you for a ride.”

As the plane landed and was coming to a stop at Ronald Reagan, a lone voice came over the loudspeaker: “Whoa, big fella. WHOA!”

After a particularly rough landing during thunderstorms in Memphis, a flight attendant on a Northwest flight announced, “Please take care when opening the overhead compartments because, after a landing like that, sure as hell everything has shifted.”

“Weather at our destination is 50 degrees with some broken clouds, but we’ll try to have them fixed before we arrive. Thank you, and remember, nobody loves you, or your money, more than Southwest Airlines.”

“Your seat cushions can be used for flotation; and, in the event of an emergency water landing, please paddle to shore and take them with our compliments.”

Another flight attendant’s comment on a less than perfect landing: “We ask you to please remain seated as Captain Kangaroo bounces us to the terminal.”

An airline pilot wrote that on this particular flight he had hammered his ship into the runway really hard. The airline had a policy which required the first officer to stand at the door while the passengers exited, smile, and give them a “Thanks for flying our airline.” He said that, in light of his bad landing, he had a hard time looking the passengers in the eye, thinking that someone would have a smart comment. Finally everyone had gotten off except for a little old lady walking with a cane. She said, “Sir, do you mind if I ask you a question?” “Why, no, Ma’am,” said the pilot. “What is it?” The little old lady said, “Did we land, or were we shot down?”

After a real crusher of a landing in Phoenix, the attendant came on the horn, “Ladies and Gentlemen, please remain in your seats until Capt. Crash and the Crew have brought the aircraft to a screeching halt against the gate. And, once the tire smoke has cleared and the warning bells are silenced, we’ll open the door and you can pick your way through the wreckage to the terminal.”

Part of a flight attendant’s arrival announcement: “We’d like to thank you folks for flying with us today. And, the next time you get the insane urge to go blasting through the skies in a pressurized metal tube, we hope you’ll think of US Airways.”

And now for MY personal favourite:

A plane was taking off from Kennedy Airport. After it reached a comfortable cruising altitude, the captain made an announcement over the intercom, “Ladies and gentlemen, this is your captain speaking. Welcome to Flight Number 293, nonstop from New York to Los Angeles. The weather ahead is good and, therefore, we should have a smooth and uneventful flight. Now sit back and relax…OH, MY GOD!”

Silence followed, and after a few minutes, the captain came back on the intercom and said, “Ladies and gentlemen, I am so sorry if I scared you earlier. While I was talking to you, the flight attendant accidentally spilled a cup of hot coffee in my lap. You should see the front of my pants!” A passenger in coach yelled, “That’s nothing. You should see the back of mine!”

Curcumin May Prevent Bone Loss

It always helps to reread studies. Yesterday I had a second look at a study on curcumin and bone resorption published in 2004 in the Journal of Immunology (http://tinyurl.com/ynuvw7), according to which curcumin may be helpful in treating secondary bone lesions associated with breast cancer and multiple myeloma and those associated with nonmalignant diseases like postmenopausal osteoporosis, Paget’s disease and rheumatoid arthritis… Researchers examined the effects of curcumin on RANKL, which stands for: Receptor Activator for Nuclear Factor-kB Ligand. Before proceeding, though, what does RANKL have to do with MM? MM cells can stimulate this receptor activator: the level of RANKL expression by myeloma cells correlates significantly with osteolytic bone disease. (See: http://tinyurl.com/36evhl) Therefore, news of any RANKL inhibitor is GOOD news. And it just so happens that, according to the abovementioned Journal of Immunology study, RANKL induces osteoclastogenesis through the activation of NF-kB, and treatment with curcumin inhibits both the NF-kB activation and osteoclastogenesis induced by RANKL. Perfect.

I also read about a 2006 University of Arizona study (head researcher: Dr. Janet Funk) on bone loss and curcumin, see http://tinyurl.com/28cpqj. Bone loss is a big problem in MM. The proliferation of MM cells reaches the point of inhibiting the regular functioning of bone-forming cells. As a result we may develop lytic lesions, which look like holes (!) and put us at a great risk for fractures, not to mention pain. Under normal circumstances, osteoclasts (about which I have written in my post on ginger) are cells that rebuild what is called fatigued bone, with the help of osteoblasts. In MM, osteoclast activity is increased (bad bad bad!), which causes bone loss instead of bone repair. (I don’t want to get bogged down in the details of this process, which is well explained here: http://tinyurl.com/2894en) I found another study with the same results, i.e., curcumin induces apoptosis of osteoclasts: http://tinyurl.com/2r38aa What is relevant for us MMers, and indeed for anybody suffering from osteoporosis, is that curcumin inhibits excessive osteoclast formation. Excellent! A few more feathers in curcumin’s rather large cap, I’d say.

Now, in all fairness, I also read a study (http://tinyurl.com/2jwu63) that seems to indicate that curcumin inhibits the proliferation and mineralization of osteoblasts. If proved true, this would mean that curcumin might have opposing effects, which, however, might end up annulling each other (I may really be going out on a limb, here! 😉 ). That is, no bone loss but no gain, either. Among other things, the following study indicates that arthritic rats treated with curcumin showed improved mineral bone density: http://tinyurl.com/2tlt38 It will be interesting to see future developments based on studies carried out on actual human beings instead of rats and cell cultures. Of course, since I have been taking 8 grams of curcumin for more than 16 months and my most recent skeletal survey showed no lesions, I have the feeling that Dr. Funk’s research will turn out to be the winner. The eternal optimist! 🙂

Siena

Veduta di Piazza del Campo con la Torre del Mangia ed il Palazzo PubblicoWe spent a lovely day in Siena, yesterday. One of my best photos is of the famous 14th century Piazza del Campo, a shell-shaped square that slopes down toward the Palazzo Pubblico and the Torre del Mangia (the bell-tower). Yesterday it was packed with tourists, loudly chattering Italian school groups and people sitting (or lying) on the ground having picnics and reading books or newspapers, yet there was still plenty of space for us to walk around. Siena is simply gorgeous.

Buon Anniversario!

My husband and I were married eight years ago today. We are celebrating our anniversary by driving to Siena later this morning and having lunch there. On the way, we may even stop briefly in San Gimignano, a small Medieval hilltop town with thirteen still-standing towers. A day spent together out in the gorgeous Tuscan countryside. And it just happens to be a beautiful sunny day. Who could ask for anything more?

Yesterday I went into town on an errand, and as I was riding home on the bus I began thinking how lucky I am to have this wonderful supportive man in my life. We have been together for more than ten years, yet I still discover new things about him. He still surprises me, my best friend and soul mate. And he makes me laugh (well, I make him laugh, too!). There is much to love about my tall dark smart and handsome Italian husband.

He has always been the one to say the words I love you. And now, after eight years, it’s my turn: Buon Anniversario, moro. Ti amo.

My Friend the Honeybee

After several attempts, I finally managed to take a decent photo of Honeybeemy camera-shy buzzing friend this morning, busily collecting nectar from my monster raspberry plant, which grew from a tiny half dead shoot that I brought back to Italy from my parents’ back yard in the U.S. a couple of years ago. Mr. Honeybee is a bit out of focus, but it’s the best I have been able to do.

Spice Without the Bite!

I would like to start out by thanking all the comment-writers. I REALLY enjoy receiving comments. For one thing, it tells me that my posts are actually being read! 😉 For another, many of your comments have given me research fodder. Case in point: a recent blog comment posted by a listserv friend about one of his newsgroup correspondents who had developed tongue cancer but couldn’t figure out HOW. He had a healthy, physically active lifestyle and had lived in Asian countries where his diet consisted mainly of hot spicy food. His oncologist told him that his tongue cancer had been caused by those very spices. The first thought that came to my mind was ridiculous!

Spices, as I have previously reported, have well-known anti-inflammatory and anti-cancer properties as well as general healing effects. However, I did go online to see if I could find a study that connected spices to any type of cancer. The result: nothing. Not one study. That doesn’t mean such a study doesn’t exist, of course, so if anybody has more success than I had this morning, please let me know. Did the cancer patient in question smoke, chew tobacco, or drink alcohol? Those are the three main listed causes for tongue cancer (that I found).

Just because you have a healthy lifestyle doesn’t mean you won’t get cancer. Indeed, a close member of my family had a terrible diet, drank quite heavily and smoked but was always as fit as a fiddle and died in her early 100s. It doesn’t make sense, but there it is.

A final point: spicy doesn’t necessarily mean HOT. I cook frequently with turmeric and other mild spices, which don’t set your mouth on fire but leave you with a pleasant sensation and aroma in your mouth: spice without the bite!

Heating Up Spices

I love the Internet! I begin with a research idea and frequently end up going in an entirely different direction. This morning, for instance, I was going to do some more research on the bioavailability of curcumin but came across a fascinating study (http://tinyurl.com/2fh26z) titled Effect of heat processing of spices on the concentrations of their bioactive principles: Turmeric (Curcuma longa), red pepper (Capsicum annuum) and black pepper (Piper nigrum). Researchers tested these spices using three different home cooking methods: in boiling water for 10 and 20 minutes, and in a pressure cooker for 10 minutes. The greatest loss of curcumin occurred in the pressure cooking process: 53 %. Good thing I don’t own a pressure cooker, I guess!

The spices were heated separately and also with tamarind powder, an acidulant, and red gram, a legume also known as pigeon pea. The losses were still significant, although the combination turmeric-tamarind reduced the pressure cooker loss to 34 %. I have been cooking with turmeric and red pepper for a long time. (Since taking curcumin with piperine capsules, though, I no longer add black pepper to my food.) I will now make sure that I don’t overcook these spices, but add them at the last minute. I certainly don’t want to lose too many of their beneficial properties.

Bee Stings May Not Hurt So Much After All!

I was looking up the medicinal properties of honey and came across a fascinating bit of news by pure coincidence. In 2006, an Iranian pharmacist administered bee venom therapy (BVT) to a patient with MM. The patient improved considerably but, as soon as the venom therapy was stopped, his markers worsened (http://tinyurl.com/3dyj3l). I have not been able to get my hands on the particular study, so if anybody has access to the March 2006 issue of the Journal of the American Apitherapy Society, please let me know! Bee venom is no joke, as I quickly discovered. It stimulates the body to release cortisol, a natural steroid, and is being used to treat multiple sclerosis and rheumatoid arthritis.

Researchers at CSIRO Molecular Science in Western Australia have been trying to modify bee venom to develop cancer treatments that would target only cancer cells, not healthy ones, and cause very few side effects. See: http://tinyurl.com/ywgmlx The main active ingredient in bee venom is melittin, a molecule with potent anti-inflammatory properties (according to Wikipedia, it appears to be 100 times stronger than hydrocortisone!) that attaches to the membranes of cells, causing them to collapse and die. The researchers’ task is to modify this molecule in order to prevent allergic/toxic reactions while maintaining intact its cancer-killing potential. The idea is to create an immunotoxin, that is, a combination of melittin and a specific cancer-killing antibody: melittin-MABs (or melittin monoclonal antibodies). If these attempts are successful, this might mean no more chemotherapy with hair loss, vomiting, weight loss, etc. Just think: only cancer cells would die.

A bit more research led me to the following study (http://tinyurl.com/yvgh3o) published in the International Journal of Oncology in 2003: a melittin/avidin conjugate was successfully used to reduce tumours both in vitro and in vivo. Avidin is a glycoprotein, by the way, and was coupled with melittin to reduce its toxicity. At any rate, this conjugate ignored healthy cells but targeted MMP-2 (matrix metalloproteinase 2), an endopeptidase that plays an important role in cancer metastasis and is active in MM, too. See, for instance, http://tinyurl.com/27m7wm, http://tinyurl.com/3exzcd and http://tinyurl.com/2uxeom

Bee venom, a possible cancer treatment? Who would have ever thought?!