Cachexia: Standard-of-cancer-care induced starvation, potential simple solution

Is cachexia a treatable neuroinflammatory condition?

Fenbendazole Can Cure Cancer presents Case Reports of people who have treated their own cancers along with other articles to help understand how fenbendazole works to treat cancer. Previous articles covering other cancers are in the Archives link. This article presents a Case Report of a woman who was undergoing self-treatment of ovarian cancer after traditional chemotherapy and radiation failed, experienced a partial resolution of her symptoms with fenbendazole but struggled to eat and maintain her weight due to the side-effects of the traditional treatments: cachexia.

According to Berardi et al. (2021), cachexia (/kə-kĕk′sē-ə/) is a multifactorial syndrome characterized by body weight loss, declining muscle mass and function, wasting, and inflammation of adipose tissues accompanied by metabolic disarrangement, anorexia, systemic inflammation, and insulin resistance. Up to 80% of cancer patients develop cachexia (Avani et al., 2018), and at least 20% of cancer-related deaths per year are directly attributed to this syndrome (Argiles et al., 2014). The overall prevalence of cachexia ranges from 40% at cancer diagnosis to 70% in advanced disease. In 20% to 25% of patients with advanced solid tumors, it is considered the primary cause of death (Baker et al., 2023). Despite this devastation there seems to be a dearth of legitimate scientific inquiry into the causes and treatment of cachexia so much so that according to Teresa Zimmerman, Ph. D. who runs the Cancer Cachexia Society says that as of now, in 2024 “unfortunately there are no effective treatments for cachexia.”

Here we present a Case Report of an 81 yr old woman named AG with metastatic ovarian cancer who was helped by fenbendazole but struggled with life-threatening cachexia caused by prior chemotherapy and radiation treatments. A quick review of the available literature suggested an obvious path to explore by conceptualizing cachexia as a neuroinflammatory condition caused by standard-of-care chemotherapeutic and/or radiological treatments intended to treat cancers.

The following Case Report is of a different style than those previously presented. It is a hybrid of summaries of emails with interspersed relevant direct quotes from family members caring for their loved one.

Case Report

81-yr-old with metastatic ovarian cancer who had received six cycles of standard chemotherapy and then 3 cycles of , mirvetuximab, soravatansine (Elahere), during the previous seven months. She had started to struggle with appetite and eating, losing weight most noticeably during the Elahere treatment. The ascites (fluid filled abdominal cysts) characteristic of ovarian cancers, as well as associated pain were persistent despite standard of care therapy.

She re-entered the hospital due to abdominal pain and extreme lack of appetite. She received updated diagnostics and was told that the cancer had spread such that end of life care was recommended. Her doctor advised against giving any sort of IV nutrition as that would supposedly “feed” the cancer. Basically, they gave up on her. From there, no doctor or nurse in the hospital viewed her as a patient that could survive due to her diagnosis. That made it difficult for the family to have any conversation with a doctor in the hospital because, while they might be concerned about a symptom or something that was impacting her, the medical team basically didn't think it mattered and would try to encourage them to change their perspective on the situation. That is, to follow their advice and let their mother go.

To gain control of the situation the family had her discharged to them with at-home hospice care. When she left the hospital, she was eating essentially zero each day and only drinking a few sips of water. Her muscles had deteriorated so much that she was completely bedridden. Doctors said that she would die in a matter of days.

About 5 weeks after the last Elahere infusion, she started fenbendazole, 222 mg per day in early December 2023. Her pain disappeared shortly thereafter and the ascites reduced in size as well. So while her pain and cancer symptoms appeared to be under control, the aftereffects of the prior year of chemotherapy were not. She had no interest in food, no appetite, severe wasting, metallic tastes in her mouth, all the classic signs of chemotherapy-induced cachexia.

Interestingly, another condition where altered gustatory and olfactory sensation and perception is disrupted is with covid infection and/or covid shots. These deficits in smell and taste are suspected to be related to inflammation in the brain. As a quick and dirty test of the inflammation idea the family performed blind smell tests with a variety of appetitive substances including coffee, grapefruit, peanut butter, brownies and apple sauce. The coffee was recognized but the others were not.

Considering the above informal test of brain inflammation plus the literature on the suspected role of inflammatory cytokines (immune cells), particularly interleukin-6 and tumor necrosis factor in cachexia (see Baker et al., 2023; Yoem & Yuo, 2022; Patra & Arora, 2012; Inui, 2001; Langhans & Hrupka, 1999; Laviano, et al., 1996; Martignoni et al., 2003 and others) it seemed reasonable to view this instance of cachexia as possibly an inflammation-based neural disorder. Inflammatory mediators such as cytokines, which include tumor necrosis factor and the interleukins, induce anorexia while increasing glucagon, cortisol, and catecholamines producing a catabolic, hypermetabolic state (Yankavenko et al., 2018).

Keep in mind that the medical team had recommended no further nutrition, no further efforts to save her and released her to family for end-of-life at-home hospice care.

Available blood tests showed very low serum vitamin D, as is common among the elderly. Vitamin D is the most important anti-inflammation substance. Without adequate vitamin D the immune system can not function properly. The fact that various studies indicate that interleukin-6 has a primary role in initiating inflammatory cascade along with the contribution of tumor necrosis factor-alpha and other cytokines in cachexia (see Baker et al., 2023, for example) supported the idea that chronic vitamin D starvation might play a role.

The following was the message sent to her children who were now managing their mother’s care:

The syndrome that is cachexia is caused either by the tumor, the chemotherapy or an interaction of both. It is unlikely to be caused by the tumor because those that don’t take chemo don’t usually develop cachexia, see the Case Reports here. So it is likely caused by the chemo.

What cachexia is characterized by is inflammation. This is an inflammation-based disorder! FYI what is elevated in cachexia are immune cells called cytokines. The specific types involved in cachexia are interleukin-6, Tumor Necrosis Factor (TNF), some interferons…all which are immune cells that cause inflammation.

Another clue. Myostatin is elevated. This substance causes muscle wasting.
Here is the exciting part. We can control the inflammation as vitamin D blocks these cytokines and, very interestingly, myostatin. [Doctors will not ever recommend or study vitamin D, even though virtually every cell in our bodies has a vitamin D receptor, because their big pharma masters will not permit it as vitD is basically free and there is no money in it].

There are a number of other strong pieces of evidence that support the vitamin D - inflammation - cachexia idea that are beyond the scope of this note. As an example, 66% of rheumatoid arthritis victims exhibit cachexia syndrome complete with inflammatory cytokines. Vitamin D helps or eliminates RA.

So, if you agree, let’s consider the cachexia as an autoimmune/inflammation problem.
Everything I’m going to suggest was mentioned in the cachexia literature as potentially helpful but they don’t have the immune system disorder framework to guide solving this issue but we do.
• Vitamin D.
• Folic Acid…potentiates the effect of the vitamin D.
• Omega 3 aka fish oil…reduces inflammation. Get the best you can find.
• Aspirin…reduces inflammation via inhibition of prostaglandins. Try a baby aspirin 81mg twice a day.
• Zinc…immune system component, 50 mg tablet zinc gluconate.
• CO2 exercises to restore energy (mitochondrial function) but also keep the oxygen going until she turns the corner here.
• Muscle building exercises. Look up some for her situation. Try 1 lb cans as weights for her to lift in various positions. She needs to get moving.

This all out attack on the inflammatory cytokines should remove what is interfering with her eating behavior.

December 18, 2023 she started on a simple, over-the-counter anti-inflammatory regimen designed to reduce as many inflammatory markers as possible:

• 5,000 IU vitamin D3 per day, increased to 10,000 IU per day two weeks later,
• One baby aspirin (81 mg) per day,
• Omega-3 fish oil capsules (1800 mg of omega-3) per day,
• Collagen supplement, one serving of Vital Proteins brand collagen supplement.

Omega 3 fatty acids aka fish oil, reduces inflammation. Eicosapentaenoic acid (EPA) is an omega-3 fatty acid that is found along with docosahexaenoic acid (DHA) in cold-water fish, including tuna and salmon. Both are potent anti-inflammatory agents.
*Aspirin, reduces inflammation via inhibition of prostaglandins.

December 26, 2023: JG “My mother requested a pancake and some grapes this morning for breakfast.  First time she has been up this early and requesting something to eat (as opposed to me pushing her to eat).  Her face definitely looks better. The Vital Proteins seems to be working out well.  She doesn't mind drinking it instead of water.

I know it is not a priority for her physical health but I'm trying to schedule her for an in-home Cancer CA125 blood test.   I feel as though if it is a good number it will provide my mother a psychological boost.   On Nov 30 she had a reading of 581 (highest reading she has had).  She started taking fenben on Dec 3.   On Dec. 12, she had a reading of 478.  She hasn't had a test since.”

December 31, 2023: JG “I did some ‘smell’ testing with her today.  Asked her to close her eyes and then I put something under her nose for 30 seconds.  Coffee, grapefruit, peanut butter, brownies, and apple sauce.  She was able to correctly identify the coffee but that was it. Overall she was more alert and awake today but still very tired and not eating much at all.”

January 9, 2024: JG “ “I also found this article, but couldn't find the clinical trial results:

https://www.urmc.rochester.edu/news/story/is-cachexia-all-greek-to-you

From the article:  "Dunne recently ran two clinical trials, looking at whether exercise and a smoothie-like nutritional supplement with whey protein, vitamin D, and high doses of omega 3 fatty acids, can boost people with cachexia. He expects to have results later this year.” ”

January 10, 2024, Ben Fen: “Well, isn’t that interesting. We’re on the right track here. As I mentioned before, I don’t think it’s the tumor putting out some mysterious substance - otherwise it would be repurposed as the latest diet fad - it’s the chemo and radiation but because of politics they can’t acknowledge that cause.

Plus, there are Case Reports here of people with no chemo and lots of tumors, that did not have cachexia.”

January 12, 2024: JG “No pain and spirits are the highest they've been in a while.  Face coloring looks good --- her face looks healthy.  I think today was day 21 of Vitamin D supplements (although we weren't at 10,000 IU/per day until about 9 days ago).  This is also day 9 of the Omega 3 Fish Oil supplements.”

January 14, 2024: JG “Today was a good day overall.  My mother had some small spoons of minestrone soup around lunch time (more than I would have expected).  She said it tasted good. She was a little more tired than the previous day but still better than a week ago.  Today was day 11 of the regimen we've been discussing.”

January 16, 2024: JG “Today was definitely one of my mother's better days.  She ate a fairly small vanilla ice cream cone in the afternoon.  She drank a good amount of liquids embellished with protein/calories…

She was alert and awake for the most I've seen. Most energy I've seen. No pain.  We got her to stand up for the first time in over 5 weeks.  Had to help her stand and then her legs gave out after only a few seconds, but it felt like progress.”

January 19, 2024: JG “The day started off very good.  She had some tomato juice, then 2 orange slices and then she requested a soft cooked potato cut up in slices with some bacon sprinkled on top (she ate half of it).”

January 24, 2024: JG “Yesterday was another fairly good day.  Helped my mother stand up for 10 seconds (twice).  She needed a lot of help but she did it.  Alert for a lot of the day.  Good amount of bed exercises and breathing exercises.  Weaning her off her supplemental oxygen. Nibbled at things throughout the day.  Wanted a little taco meat at the end of the day. 

Today has started off well too.  She drank a decent sized cup of vegetable juice.”

January 25, 2024: JG “Another very good day for my mother (day 21 of vit D 10,000 IU).  We took her off supplemental oxygen today.  Very alert.  Nibbled at a bunch of things throughout the day.  Had cravings for different foods (even though she didn't eat very much when we gave them to her). She wasn't up for standing but we did bed and breathing exercises. I think tomorrow she'll be up for standing again.”

January 26, 2024: JG “Another good day today.  My mother was requesting different types of food.  Still only eating small amounts but she definitely is having cravings for certain tastes it seems.  Alert a good amount.  A good amount of exercise as well.”

January 28, 2024: JG “Another good day overall.  Very alert and awake. Good amount of exercise. Ate some bites here and there but still not a whole lot.  Did say she was "hungry" at one point though.”

February 9, 2024: JG “My mother is definitely expressing “hunger” and eating far more than 3 weeks ago.  She wanted some lobster bisque, potato salad, yogurt, plum, and fried shrimp today.  Still small amounts but eating.”

A few days afterward AG experienced a health emergency that required hospitalization. Tragically, she died a few days later of an untreated infection, completely unrelated to her cancer.

Summary

This story is one of remarkable dedication of the children to do all that was within their power to save their mother after traditional medicine had advised them to essentially let AG starve to death after failed chemotherapy and radiation cancer treatments created the conditions for a state of cachexia. AG was showing progress toward eradicating her cancer with fenbendazole when starvation related to cachexia became life threatening. Cancer was not AG’s biggest threat, starvation was.

There was very little guidance in the literature that was of any use regarding effective treatments for cachexia. Which is surprising/not surprising given its prevalence and clear cause: traditional chemotherapy and radiation. If, as mentioned above, up to 70% of patients with advanced cancers, meaning lots of chemo and radiation, get cachexia (Argiles et al., 2014) it is not a good advertisement for traditional treatments. Nevertheless, scanning the data was available it was clear that cachexia was likely a neuroinflammatory condition caused by chemotherapy and/or radiation. The hunger and satiety centers in the hypothalamus of the brain are directly connected to the olfactory bulbs. The thinking was that if olfactory function was disrupted by neuroinflammation that could be the tip of the iceberg regarding hypothalamic dysfunction caused by chemo/radiation induced inflammation. That was the rationale for the olfactory tests. AG’s olfactory function was largely absent so, based on the supposed roles of inflammatory cytokines in cachexia (see Bernardi et al., 2021 Figure above, N.B., *we do not agree that the tumor upregulates IL-6, TNF, Myostatin etc.) the family started an over-the-counter, best available methods, anti-inflammation program to try to reduce inflammation in the brain as rapidly as possible.

Changing the course of cachexia felt like changing the course of the Titanic. First, exacerbating the damage had to stop. AG completed all the available rounds of treatment and was released home to die. So the supposed cause was stopped. Second, not eating is a clear and present danger to immediate survival. Cachexia would kill her before cancer ever could. There was a race-against-the-clock urgency to try every reasonable method to mitigate the inflammation. As you have seen from the messages above, AG did slowly but surely start to eat more, and would express feelings of hunger and request various types of foods. AG’s untimely death from an unrelated infection cut short her story. However, it did appear that she would turn the corner any day now until she didn’t.

What Have We Learned About Cachexia from AG?

Yes, this is a single instance limiting how much confidence can be obtained from what was tried. However, the interventions were simple, inexpensive, safe and painless limiting the downsides of application to others. As these decisions were made under emergency conditions: AG was being denied nutrition in what was clearly an effort to euthanize her and the family intervened by discharging her to their care, best efforts were made to obtain readily available anti-inflammatories and institute common sense best practices regarding administration of those substances in an effort to save her.

The starvation process that characterizes cachexia develops over time from repeated chemotherapy and radiation treatments. AG was in the throes of late stage cachexia. We have to assume that inflammatory markers were greatly elevated and that neuroinflammatory processes were disrupting normal functioning of hunger and satiety centers presumably in the hypothalamic region. The fact that simple anti-inflammatory interventions appeared to have any effect is noteworthy given the dire, late stage circumstances. These post hoc interventions raise the question of whether cachexia is a condition better prevented than treated.

AG was without measurable vitamin D as her 25(OH)D3 level was nil, which is unfortunately all too common among the elderly. Chronic vitamin D starvation causes dysregulation of the immune system, broadly defined, which is a precondition for maladaptive inflammation throughout the body, including the brain. To the extent that traditional cancer treatments cause brain inflammation, and they do (see Berardi, et al., 2021), administering those treatments to vitamin D compromised patients may set the stage for cachexia.

The first suggestion is to optimize the serum vitamin D levels of cancer patients’ and the elderly, in general, to reduce the likelihood of the development of cachexia should traditional cancer treatments be used. Currently, optimal vitamin D serum levels are the subject of some debate but somewhere between 80-100 ng/ml is a good target**. These levels should be achieved with supplementation of 8000 - 10,000 IU vitamin D3 per day. There is a difference between raising vitamin D levels temporarily vs. a state of chronic vitamin D optimization in regard to immune system function. Starting a vitamin D supplementation program now, before you need it, may be the best course of action.

Second, due to misinformation and bad advice like the RDA, the US population is a state somewhere between chronic vitamin D deficiency and chronic vitamin D starvation (Grant, 2024). If population-wide serum vitamin D level was raised to optimal ranges most autoimmune diseases and most cancers would never develop. Hopefully with the new administration, RFK Jr., and the Make America Healthy Again mandate the Silent War Against Vitamin D that has been waged for the last 50 years by Big Pharma and its stooges at the Federal level can be over.

Third, clearly cachexia is a fatal side effect of traditional chemo and radiation therapy. There is no appetite in traditional medicine to acknowledge that causal link because it is bad for business. In AG’s case, her cancer was on the run due to fenbendazole. The more serious issue she had to contend with was the cachexia caused by the six rounds of chemotherapy. In AG’s case the treatment was definitely more deadly than the disease.

Methods to Minimize the Risk of Cachexia

• Optimize serum level of vitamin D to reduce risk of cancer by optimizing immune function.

• If a loved one is involved in traditional cancer treatments, optimize vitamin D level to bias against chemo and/or radiation induced neuroinflammation that causes cachexia.

• In light of the risks of the cancer therapies being offered, consider side-effect free treatments like fenbendazole, that actually work (Baghli, Makis, Marik et al., 2024) and won’t cause life threatening conditions like cachexia.

*Chemo/Radiation causes cachexia not the tumor. Why? Because many of the Case Reports presented here did not use any chemotherapy and/or radiation, just fenbendazole, and there was never any hint of cachexia it strongly appears that the standard-of-care radiotherapeutic and chemotherapeutic treatments cause cachexia.

**The US RDA of 600 IU vitamin D3/day is the amount required to prevent bones from crumbling. This recommendation is a total joke put out by the “Institute of Medicine” which is comprised of Big Pharma stooges paid to undermine the nation’s health status. Raising population-wide vitamin D status to optimal levels will be a great first step toward Making America Healthy Again. As vitamin D is kryptonite to most of Big Pharma’s treatments as optimal levels help prevent autoimmune, metabolic and metastatic disease in the first place, expect an epic battle to villify vitamin D and the sun as the Make America Healthy Again team stimulates change.

Author’s Note: This Case Report is especially difficult to process given that one of the authors’ mothers starved to death in 2003 following radiation treatments for cervical cancer. Cachexia is a horrible side effect of traditional cancer treatments. Recognizing the cause is the first step in fixing the problem.

References

Advani S.M., Advani P.G., VonVille H.M., Jafri S.H. Pharmacological management of cachexia in adult cancer patients: A systematic review of clinical trials. BMC Cancer. 2018;18:1174. doi: 10.1186/s12885-018-5080-4.

Argiles J.M., Busquets S., Stemmler B., Lopez-Soriano F.J. Cancer cachexia: Understanding the molecular basis. Nat. Rev. Cancer. 2014;14:754–762. doi: 10.1038/nrc3829.

Baghli I, et al. (2024) Targeting the Mitochondrial-Stem Cell Connection in Cancer Treatment: A Hybrid Orthomolecular Protocol. J Orthomol Med. 39.3

Baker R J, Syed K, Minteer JF. Cachexia. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470208/

Berardi E, Madaro L, Lozanoska-Ochser B, et al. A Pound of Flesh: What Cachexia Is and What It Is Not. Diagnostics (Basel). 2021;11(1):116. Published 2021 Jan 12. doi:10.3390/diagnostics11010116

Devaraj S., O’Keefe G., Jialal I. Defining the proinflammatory phenotype using high sensitive C-reactive protein levels as the biomarker. J. Clin. Endocrinol. Metab. 2005;90:4549–4554. doi: 10.1210/jc.2005-0069.

Grant, W. B. (2024) “Cancer Incidence Rates in the US in 2016–2020 with Respect to Solar UVB Doses, Diabetes and Obesity Prevalence, Lung Cancer Incidence Rates, and Alcohol Consumption: An Ecological Study.” Nutrients. 16(10) https://doi.org/10.3390/nu16101450.

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Langhans W, Hrupka B. Interleukins and tumor necrosis factor as inhibitors of food intake. Neuropeptides. 1999;33:415–424. doi: 10.1054/npep.1999.0048.

Laviano A, et al. Cracking the riddle of cancer anorexia. Nutrition. 1996;12:706–710.

Martignoni ME, Kunze P, Friess H. Cancer cachexia. Mol. Cancer. 2003;2:36. doi: 10.1186/1476-4598-2-36.

Patra SK, Arora S. Integrative role of neuropeptides and cytokines in cancer anorexia-cachexia syndrome. Clin. Chim. Acta. 2012;413:1025–1034. doi: 10.1016/j.cca.2011.12.008.

Powrozek T, et al. Relationship between TNF-alpha -1031T/C gene polymorphism, plasma level of TNF-alpha, and risk of cachexia in head and neck cancer patients. J. Cancer Res. Clin. Oncol. 2018;144:1423–1434. doi: 10.1007/s00432-018-2679-4.

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Items Included in All Posts

Fenbendazole vs. Mebendazole vs. Albendazole vs. Flubendazole: The benzimidazoles are very similar chemically and they have very similar mechanisms of action with respect to disrupting microtubule function, specifically defined as binding to the colchicine-sensitive site of the beta subunit of helminithic (parasite) tubulin thereby disrupting binding of that beta unit with the alpha unit of tubulin which blocks intracellular transport and glucose absorption (Guerini et al., 2019). If someone asks you how fenbendazole kills the cancer cells, the answer is in italics in the previous sentence.

The class of drugs known as benzimidazoles includes fenbendazole, mebendazole, albendazole and flubendazole. Mebendazole is the form that is approved for human use while fenbendazole is approved for veterinary use. The main difference is the cost. Mebendazole is expensive ~$555 per 100 mg pill, while fenbendazole is inexpensive ~48 cents per 222 mg free powder dose (Williams, 2019). As you may recall, albendazole is the form used to treat intestinal parasites in India and these cost 2 cents per pill. FYI, to illustrate how Americans are screwed by Big Pharma, two pills of mebendazole cost just $4 in the UK, 27 cents per 100 mg pill in India and $555 per 100 mg pill in the US.

While most of the pre-clinical research uses mebendazole, probably because it is the FDA-approved-for-humans form of fenbendazole, virtually all of the self-treating clinical reports involve the use of fenbendazole. Because the pre-clinical cancer studies use mebendazole (ironically the human form of fenbendazole) and humans self-treat their cancers with fenbendazole (the animal form of mebendazole) it is very reasonable to assume that mebendazole and fenbendazole are functional equivalents with respect to cancer. It would be helpful if future pre-clinical and clinical investigations simply used fenbendazole as a practical matter. For the purposes of this Substack, fenbendazole, mebendazole and albendazole are used interchangably.

Where to get fenbendazole
In our experience and the experiences of those that write in, it appears that the three readily available brands of fenbendazole (Panacur-C, SafeGard, FenBen Labs) are equally effective. Panacur-C can be obtained locally in pet stores, while they all can be obtained from Amazon. The article in this Substack on Questions & Answers discusses the brands of fenbendazole in detail and shows photos of the various brands referenced.

If you would like to report your experiences with fenbendazole you can do so privately by email myfenbendazole@proton.me or more publicly in the Comments section in any of the articles. Also, if you know of people who’ve tried fenbendazole, and it didn’t work, we’d be especially interested in hearing from you now. Understanding the conditions and factors that enhance or impede the success of fenbendazole in treating cancer are valuable.

Disclaimer:
Statements on this website have not been evaluated by the Food and Drug Administration. The contents of this website is for educational and informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis or treatment. This website does not provide any kind of health or medical advice of any kind. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. The case reports presented reflect the real-life experiences and opinions of other readers or users of the website. The experiences of those readers or users are personal to those particular readers/users and may not necessarily be representative of all readers/users. We do not claim, and you should not assume, that all other readers/users will have the same experiences. Do you own research, consult with relevant medical professionals before attempting to self-treat for any condition.