DNC News:  Fish Oil and Cachexia

Subject:  Fish oil concentrates play a role in all areas of cancer treatment

Since Prairie Home Companion was running reruns a few weeks ago I tried doing the same with this Newsletter.  I pulled up an old article on fish oil and then made a mistake.

 "I wonder what's new?" I thought.  Two hours later, I'd downloaded 11 pages of new abstracts knew the old version was obsolete.
Who said the internet saves time?

In cancer treatment the dreaded word is cachexia. It comes from a Greek word meaning something like, "bad habit of the body."  Cachexia is the word used to describe the generalized emaciated, debilitated state seen in patients with advanced chronic disease, especially cancer.  It is a result of changes in metabolism combined with loss of appetite. It is a major factor in the illness and death of patients with advanced cancer. Something happens as cancer advances that changes one's chemistry drastically. Their bodies can no longer pull energy out of the food they eat.  It takes more and more calories just to not maintain weight. It's like having bad sparkplugs, not running on all your cylinders and getting lousy gas mileage.

Back in 1999 Barber and his gang in Edinburgh published a study on patients with pancreatic cancer who they fed supplemental fish oil to. Twenty patients with inoperable pancreatic cancer were given a nutritional supplement to drink twice a day each of which contained about 300 calories, 16 grams of protein and 1 gram of EPA derived from fish oil.  At the start of the study patients were losing weight at about 6 pounds per month.  Once they started the fish oil enriched supplement they stopped losing weight and 3 weeks later had gained 2 pounds and at 7 weeks, 4 pounds.

"In contrast to previous studies of oral conventional nutritional supplements in weight-losing cancer patients, this study suggests that an EPA-enriched supplement may reverse cachexia in advanced pancreatic cancer." [1]

That was what the first newsletter was about.  Now what's is new?

That same year, Burns and a crew of researchers from Iowa City published a study with leukemia patients. Using 22 patients who had lost at least 2% of their body weight the prior month, they gave escalating doses of fish oil.  The maximum tolerated dose was 0.3 g/kg per day.  That's about 21 one gram capsules a day for a 150 pound person! No toxic reactions were reported just diarrhea and indigestion." [2]

A study in April, 2000, done by Ogilvie and a pack of researchers at the veterinary school in Fort Collins , looked at dogs with lymphoma. They added fish oil to the food of dogs with Stage III lymphoma and were able to significantly increase the disease free intervals and survival times.  [3]

Yam and two of his chevre at the Weizmann Institute compared the effects of adding fish oil, with and without the antioxidant vitamins E and C to mice with lung cancer who were being treated with cisplatin. Plain fish oil and the fish oil, E and C combination were useful, slowing tumor growth and metastasis. The plain fish oil worked best.  The ad vitamin E and C to the oil lessened the benefit.  At least part of the anti tumor effect of the fish oil was one of oxidative damage. [4]

This makes sense.  Fish oil goes rancid easily. A single experience with the taste of rancid oil is can last most people a life time.  Oil taken up by cells, especially cancer cells because they are fast growing, is incorporated into the cell membranes making them more sensitive to oxidative damage from chemo or radiation.

In 2001, Barber and the Edinburgh return with another pancreatic cancer study.
As in their first study, they recruited patients with pancreatic cancer who were rapidly losing weight, had them drink a protein/ fish oil shake twice a day and watched them begin to put on weight.  Again they used relatively low dose fish oil, 2 grams a day, and started to see an effect in about 3 weeks. This time rather than just measuring weight gain, they watched a host of esoteric chemicals associated with cachexia and saw them decrease as well. Improvements were seen in interleukin (IL)-6 and its soluble receptor tumor necrosis factor receptors I and II, cortisol, insulin, and leptin, peripheral blood mononuclear cell production of IL-1 beta, IL-6, and tumor necrosis factor, and urinary excretion of proteolysis inducing factor.  [5] Be glad we aren't being tested on these names...

About a year and a half ago, in July, 2002, Hardman and his boys in Louisiana , added some more information about how fish oil works.  Using breast cancer in mice treated with chemotherapy (doxycyclin) as a model, they showed that adding fish oil with or without vitamin C effected glutathione peroxidase levels.  I'll skip the details here but they are thinking the fish oil's actions are at least two-fold: increasing oxidative damage and secondly lowering glutathione peroxidase.  Don't worry that vitamin E will interfere with the fish oil you take, they used huge HUGE doses of vitamin E to decrease the fish oil benefit, about 2000 mg/kg.  Scaled to human size that is almost 400 capsules a day.  [6]

In October 2002, a study was published using rats with fibrosarcoma treated with huge amounts of eicosapentanoic acid (a key constituent of fish oil). They were force fed huge doses (5 grams per kilogram) which if translated into human scale would be 350 1 gram capsules a day. That's about a cup and a half of oil. Force fed is a key word here. After a month their tumors had shrunk by 25%.  [7] Big deal as no one will ever take that large a dose.

Last November, Hardman wrote a review article and summarized current understanding of the role fish oil plays in cancer treatment:
"The results of animal studies have demonstrated that the consumption of omega-3 fatty acids can slow the growth of cancer xenografts, increase the efficacy of chemotherapy and reduce the side effects of the chemotherapy or of the cancer. Molecular mechanisms postulated to contribute to the multiple benefits of omega-3 fatty acids include
1) suppressing the expression of cyclooxygenase-2 in tumors, thus decreasing proliferation of cancer cells and reducing angiogenesis in the tumor;
2) decreasing the expression of AP-1 and ras, two oncogenes implicated in tumor promotion;
3) inducing differentiation of cancer cells;
4) suppressing nuclear factor-kappaB activation and bcl-2 expression, thus allowing apoptosis of cancer cells; and
5) reducing cancer-induced cachexia.
It seems reasonable to assume that after appropriate cancer therapy, consumption of omega-3 fatty acids might slow or stop the growth of metastatic cancer cells, increase longevity of cancer patients and improve their quality of life."  [8]

In the past I have often stalled incorporating fish oils into the plans of cancer patients until we saw weight loss.  This was clearly in error as it is beginning to look appropriate at all stages of treatment.

While I am copying quotes, here's another one:
"The implications for this research are profound because there are few nutritional therapies available that have the potential to be (as) clinically effective in malignancies and other chronic inflammatory conditions as omega-3 FA."  [9]

Now of course not all news is good news.  I found one negative study in which showed no benefit using fish oil with patients.  Bruera and his good old boys in Texas tried giving patients fish oil for 14 days and were not able to show any statistically significant improvement.  [10]   All I have is their abstract so I can't tell you if there was a non- statistically significant improvement which might have become significant if the study had run longer.

Based on this review all cancer patients should be taking fish oil concentrates.  Don't expect results overnight.  The short study that only ran 14 days was the only negative one I noticed.  Others ran 3 weeks and longer and had good results.  The most effective studies, the ones with pancreatic cancer incorporated the fish oil into a protein supplement drink.  When the concern is cachexia, it makes sense to do it this way.  It may be that the fish oil by some still unknown mechanism is able to temporarily improve metabolic function, get all the cylinders firing again.  If a good source of protein is available during this window of opportunity, the body may have a chance of using it.
I frequently suggest fruit smoothies using frozen berries, protein powder and about 1 Tablespoon of fish oil along with other specific nutrients.  As to which protein powder, that's not a simple question but will be the subject of another letter.

Stay tuned for more attempts at rerunning old newsletters.



references:
 1. Br J Cancer. 1999 Sep;81(1):80-6. 
The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer.
Barber MD, Ross JA, Voss AC, Tisdale MJ, Fearon KC.

2.  Clin Cancer Res. 1999 Dec;5(12):3942-7.   
Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473.
Burns CP, Halabi S, Clamon GH, Hars V, Wagner BA, Hohl RJ, Lester E, Kirshner JJ, Vinciguerra V, Paskett E.
 3. Cancer. 2000 Apr 15;88(8):1916-28.  
Effect of fish oil, arginine, and doxorubicin chemotherapy on remission and survival time for dogs with lymphoma: a double-blind, randomized placebo-controlled study.
Ogilvie GK, Fettman MJ, Mallinckrodt CH, Walton JA, Hansen RA, Davenport DJ, Gross KL, Richardson KL, Rogers Q, Hand MS.
 4.  Cancer Chemother Pharmacol. 2001;47(1):34-40
Suppression of tumor growth and metastasis by dietary fish oil combined with vitamins E and C and cisplatin.
Yam D, Peled A, Shinitzky M.
 5. Nutr Cancer. 2001;40(2):118-24 
Effect of a fish oil-enriched nutritional supplement on metabolic mediators in patients with pancreatic cancer cachexia.
Barber MD, Fearon KC, Tisdale MJ, McMillan DC , Ross JA.
 6.  Cancer Cell Int. 2002 Jul 17;2(1):10. 
Role of lipid peroxidation and antioxidant enzymes in omega 3 fatty acids induced suppression of breast cancer xenograft growth in mice.
Hardman WE, Munoz J Jr, Cameron IL.
7.   JPEN J Parenter Enteral Nutr. 2002 Sep-Oct;26(5):291-7. 
Eicosapentaenoic acid supplementation reduces tumor volume and attenuates cachexia in a rat model of progressive non-metastasizing malignancy.
Jho DH, Babcock TA, Tevar R, Helton WS, Espat NJ .
 8.  J Nutr. 2002 Nov;132(11 Suppl):3508S-3512S. 
Omega-3 fatty acids to augment cancer therapy.
Hardman WE.
 9. Am Surg. 2003 Jan;69(1):32-6
Omega-3 fatty acids: implications for the treatment of tumor-associated inflammation.
Jho D, Babcock TA, Helton WS, Espat NJ .
 10. J Clin Oncol. 2003 Jan 1;21(1):129-34. 
Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: a double-blind, placebo-controlled study.
Bruera E, Strasser F, Palmer JL, Willey J, Calder K, Amyotte G, Baracos V.


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