Cachexia

[lysanderswife]

My husband was diagnosed this month with S4 liver cancer. Hal is very weak because he has cachexia which is muscle wasting. My main goal right now is to reverse that but there is basically no info online about this. Google scrubbed everything good.

Someone suggested we look at hydrazine sulfate which may prevent the body from making sugar that cancer cells need to grow. It is thought that cachexia occurs because cancer is using too much of the body’s sugar, preventing healthy cells from getting what they need to live. Then, as muscle breaks down, it makes sugar that the cancer cells use to grow.

I’m wondering if I FEED him sugar, can I stop the muscle wasting? Cachexia is likely to kill him before the cancer gets a chance. I’m reading everything I can while I take care of him at home. Fortunately I work at home.

He’s on everything: ivermectin, fenben, cyproheptadine, melatonin, DMSO, a million things. The protocol is here if anyone has feedback: https://docs.google.com/spreadsheets/d/1j0rB_7hVmYbfSutn7W_sr_fHupVVlVrxasqlws4vTlQ/edit

Would love to hear ideas for reversing this cachexia! Thank you.

PS. Unjabbed, antivax since 1995 when our 4yo had a stroke after his Hep B.

• This topic was modified 1 week, 3 days ago by lysanderswife.

[Zack-Vegas]

The idea of feeding of extra sugar is a pretty good one.  Ray Peat talked about French doctors in the 1800s using extra sugar to sustain the weight of diabetics that were wasting away-

https://raypeat.com/articles/articles/glucose-sucrose-diabetes.shtml

In 1857, M. Piorry in Paris and William Budd in Bristol, England, reasoned that if a patient was losing a pound of sugar every day in 10 liters of urine, and was losing weight very rapidly, and had an intense craving for sugar, it would be reasonable to replace some of the lost sugar, simply because the quick weight loss of diabetes invariably led to death. Keeping patients from eating what they craved seemed both cruel and futile.

After Budd’s detailed reports of a woman’s progressive recovery over a period of several weeks when he prescribed 8 ounces of sugar every day, along with a normal diet including beef and beef broth, a London physician, Thomas Williams, wrote sarcastically about Budd’s metaphysical ideas, and reported his own trial of a diet that he described as similar to Budd’s. But after two or three days he decided his patients were getting worse, and stopped the experiment.

Williams’ publication was presented as a scientific refutation of Budd’s deluded homeopathic ideas, but Budd hadn’t explained his experiment as anything more than an attempt to slow the patient’s death from wasting which was sure to be the result of losing so much sugar in the urine. The following year Budd described another patient, a young man who had become too weak to work and who was losing weight at an extreme rate. Budd’s prescription included 8 ounces of white sugar and 4 ounces of honey every day, and again, instead of increasing the amount of glucose in the urine, the amount decreased quickly as the patient began eating almost as much sugar as was being lost initially, and then as the loss of sugar in the urine decreased, the patient gained weight and recovered his strength.

Drs. Budd and Piorry described patients recovering from an incurable disease, and that has usually been enough to make the medical profession antagonistic. Even when a physician has himself diagnosed diabetes and told a patient that it would be necessary to inject insulin for the rest of his life, if that patient recovers by changing his diet, the physician will typically say that the diagnosis was wrong, because diabetes is incurable.

********

I’ll link a second Newsletter below.

• This reply was modified 1 week, 3 days ago by Zack-Vegas.

[Zack-Vegas]

Here’s another newsletter where Peat talks about the same idea-

https://raypeat.com/articles/articles/sugar-issues.shtml

In an earlier newsletter, I wrote about P. A. Piorry in Paris, in 1864, and Dr. William Budd in England, in 1867, who treated diabetes by adding a large amount of ordinary sugar, sucrose, to the patient’s diet. Glucose was known to be the sugar appearing in the diabetics’ urine, but sucrose consists of half glucose, and half fructose. In 1874, E. Kulz in Germany reported that diabetics could assimilate fructose better than glucose. In the next decades there were several more reports on the benefits of feeding fructose, including the reduction of glucose in the urine. With the discovery of insulin in 1922, fructose therapy was practically forgotten, until the 1950s when new manufacturing techniques began to make it economical to use.

[Zack-Vegas]

Some other thoughts…..

Muscle wasting is a loss of protein and nitrogen.  If this is in part due to gluconeogenesis raging out of control, then it makes sense that increasing carbs in general and sucrose in particular could be very useful to slow and reverse the rapid weight and muscle loss.  A higher protein intake would also be very useful, and it really could be any kind, if muscle loss is rapid.  Milk, meat, gelatin, protein supplements, really, whatever he can eat, and eat in higher amounts.  I think  some sort of protein shake could be useful, at least for a time.

Another possibly useful supplement is urea.  It might be able to normalize nitrogen balance fast, and in fairly low amounts, it has about 2.5 times the nitrogen value of protein (eg, 30 grams of urea has the same nitrogen value as 80 grams of protein).  The only issue, and it’s a big one, is that the taste is horrid.

Cyproheptadine might be one of the best drugs he’s on.  What is the dose?  You might want to ask your doctors about increasing the dose, as it is notorious for stimulating appetite, and helping people to put on weight.  You can go look at some of the cyproheptadine threats on the old RPF for confirmation of this, or just do a google search.  So many people report putting on something like 20, 30, 40 pounds while on cypro, even some bodybuilders use it for this purpose.  Many times, it’s seen as a negative, but this would be a huge positive for in your husbands case.

Lastly, does he have any issues eating?  Is he not hungry?  Can he not hold food down or digest it properly?  Wasting can be a viscious circle, where you aren’t that hungry, you start to lose weight, and then your body starts to shut down things like digestive processes, which makes it harder to eat, which can make weight loss accelerate, and so on.  In cases like this, something like an anti nausea med like Ondansetron (which is anti serotonin like Cypro), or things that stimulate stomach acid production, like salt and maybe something like Beatine HCL, could also be possibilities to look into.

[Lilac]

You can search lowtoxinforum.com for cachexia. Are you registered? You might have to pay a fee. I’m not sure what the policy is now. Here is an initial post by Haidut/Georgi Dinkov:

 

Another study linking chronic inflammation to cancer and its signature muscle wasting condition known as cachexia. Yet another piece of the puzzle in how aspirin prevents and maybe even treats cancer.
This study is also interesting b/c it found that that the current medical opinion vilifying fat deposits as bad and trying to burn them is actually the exact opposite of what should be done. It looks like, for cancer patients at least, regular white fat around the butt and belly is actually very beneficial.

http://news.sciencemag.org/biology/2014 … r-patients

“In the mouse models, the researchers were able to link the process [cachexia] to the systemic inflammation that’s often seen in cancer patients. They implicated interleukin-6 (IL-6), a cell signaling protein involved in stimulating the body’s immune response to inflammation. They then showed that anti-inflammatory drugs may prevent the white fat browning that precedes cancer cachexia and the wasting syndrome itself, the team reports online this week in Cell Metabolism. Bruce Spiegelman, a cell biologist at the Dana-Farber Cancer Institute in Boston, recently reached a very similar conclusion in his own lab and published the result in Nature. Both papers, he says, “end any question that activation of fat browning is definitely part of cancer cachexia, at least in terms of animal models, and are pretty suggestive in people with cancer.” Spiegelman’s lab used a different mouse model of cancer cachexia and searched for genetic changes in tumor cell function, homing in on a distinct molecular factor, tumor-derived parathyroid-hormone-related protein (PTHrP). When his group neutralized this protein in mice, “muscle wasting and cachexia were alleviated but not stopped,” Spiegelman says. He says that means other factors are likely involved, possibly IL-6.”

[Lilac]

Here is another post by Haidut:

 

The title of the post is a bit strange but it is pretty much what the study below found. Just like the SSRI drugs, the mechanism of action of statins is (officially) not really known. The official version for the antidepressant effects of SSRI drugs was that they increase intracellular levels of serotonin. The latter part is true, but that is not what explains the benefits of SSRI drugs. Their lesser known effects on increasing allopregnanolone levels in the brain (by increasing 3a-HSD activity) and lowering cortisol levels (by blocking 5-HT2C receptor) are the real mechanism of action. Obviously, admitting that a supposedly serotonergic drug achieves its antidepressant effects by blocking the 5-HT2C receptor does not sit well with Big Pharma, so the official study continues to be that serotonin helps alleviate depression.
What does that have to do with statins? Well, a few large trials did appear to show benefit from (some, not all) statins for preventing CVD development. The official story was that this benefit was due to the statins lowering cholesterol levels. However, a lesser known effects of statins that has been kept well-hidden from the public is that some statin drugs are actually antagonists of the endotoxin receptor TLR4. Given the role of TLR4 in virtually all chronic diseases but especially CVD, the observed benefit from statins suddenly become very clear. However, just like in the case of SSRI drugs, that does not mean that suddenly statins become attractive and beneficial drugs. Their negative systemic effects of cholesterol-lowering likely vastly outweigh the benefits these drugs provide by blocking endotoxin.
And this brings us to the main topic of the study below, which is that TLR4 is apparently crucial for the tissue wasting commonly seen in cancer and known as cachexia. This wasting is actually seen not only in cancer but in a number of other chronic conditions including AIDS, IBD, ALS, Huntington’s, and even as part of the general aging process. As the study below found, blocking TLR4 with the statin drug Lipitor (atorvastatin) blocked the sating seen in cancer. There are many other, possibly safer, ways to block TLR4 including with chemicals like ketotifen, cyproheptadine, emodin, etc or even with food like saturated fats, vitamin A, B2, D, etc. Interestingly, both ketotifen and cyproheptadine have successfully been used to prevent/treat cancer cachexia in humans. Given the renewed interest in TLR4 antagonsits, I would not be surprised if both drugs get repurposed and their prices skyrocket. Cyproheptadine is already next to impossible to get even by prescription in most Western countries.
And last but not least, the study confirmed earlier findings that the porcess of cachexia is associated with the so-called browning of the adipose tissue, which is is also caused by increased adrenaline, exposure to cold, and pretty much any chronic exposure to stress. This is one of the main reasons I kept arguing against cold-exposure thermogenesis as a way to lose fat. It seems to be all the rage now, and is promoted by people like Dr. Chris Kresser.
Treating SIBO, Cold Thermogenesis, and When to Take Probiotics | RHR
For a healthy person, occasional cold exposure is probably OK, but if there is a dormant tumor somewhere in the body this additional stress can likely re-activate it and start the cachectic process.
New molecular auto-control system to avoid an excessive brown adipose tissue activity
“…An excessive activity of the brown adipose tissue creates pathological picture associated to an uncontrolled energetic waste and fast weight loss (cachexia, etc.) in patients with tumours. There are many enigmas about a process, that despite being within the clinical field, hardens the recovery of the affected patients by burning when the energy waste and activity of the brown adipose tissue skyrockets.”

The article above tries to link the cachexia to drugs like DNP, but they are not known to lead to the same process as the cancer-drive cachexia. The rapid rise in body temp driven by DNP serves as a brake on how much the drug can be abused. If it is abused the person most often dies of hyperthermia, long before cachexia sets in, unlike the cancer patients where cachexia IS the actual cause of death.

Research Grants 15/19259-0 – Biological Sciences, Biochemistry – BV FAPESP
Drug used to control cholesterol found effective against cancer-associated cachexia

“…TLR4 (toll-like receptor 4) is a protein that plays a key role in pathogen recognition, innate immunity activation and inflammatory responses. Because obesity, similar to cachexia, is associated with systemic inflammation, the authors of the study suspected that TLR4 might be linked to adipose tissue remodeling. “We set out to associate the action of TLR4 with cachexia,” Batista said. In a mouse model, the researchers used both genetic ablation and pharmacological inhibition of a receptor similar to human TLR4. They next induced lung cancer in genetically modified mice (without TLR4) and in control wild-type mice (with TLR4). “We found that 28 days after the inoculation of cancer cells in their lungs, the wild-type mice with TLR4 had lost 12% of their body weight, a classic sign of cachexia,” Batista said. Cachexia was less severe in mice without TLR4. “These animals lost less weight and muscle mass. They also lived longer, even though tumor growth was the same as in the control group. It’s also important to note that no lung metastasis was detected among the genetically modified mice,” Batista said. An analysis of adipose cells from the two groups showed that browning had occurred in the control mice with TLR4. This process likely led to accelerated weight loss. “Adipose tissue was less altered in the genetically modified mice without TLR4. In other words, lack of the receptor significantly blocked the adipose tissue browning effect,” Batista said.”

“…Atorvastatin is an inexpensive drug widely used to control cholesterol. Research performed in recent years has described the anti-inflammatory effects of atorvastatin, including the downregulation of TLR4 gene expression. The authors of the study decided to use a preclinical model to determine whether atorvastatin affects the development of cachexia in wild-type mice with TLR4 in a similar manner to its effect on genetically modified mice without TLR4. They induced lung cancer in two groups of wild-type mice. In the group not treated with atorvastatin, tumors developed, and symptoms of cachexia were observed. In mice treated with atorvastatin, the result was even better than that in genetically modified mice without TLR4. “Treatment with atorvastatin proved effective in extending survival, attenuating adipose tissue remodeling and reducing tumor growth [by 49.7%] in comparison with a control group not treated with the drug. We showed that atorvastatin had a direct effect on the action of TLR4, which inhibited adipose tissue browning and reduced tumor growth,” Batista said.”

[Lilac]

Haidut:

Vitamin B3 counteracts (cancer) cachexia, by restoring NAD+ levels
As many of my readers know, the majority of cancer patients do not succumb from the actual tumor burden, but as a result of (usually in that order) cachexia, immunocompromise from radiation/chemotherapy, hospital-acquired infection, and/or cytokine storm after surgery for removing the tumor. Of these, cachexia is perhaps the most pernicious as its cause is considered unknown, it affects all organs/tissues, and no remedies exist to even mitigate it. Cachexia is also the main cause of death in other “wasting” conditions, including sarcopenia of advanced age, diabetes type I, untreated chronic inflammatory diseases such as Crohn’s disease, multiple sclerosis, prolonged bedridden states, etc. If decline in NAD+ levels is the main reason behind cachexia in general, then the findings of this study may provide a cheap, safe and widely available remedy that can affect a significant percentage of chronically ill people worldwide. This is why I put the “cancer” word in the title in brackets, as the findings of this study likely apply to cachexia of any origin, not just cancer.

The study below demonstrates that niacin at a provably non-toxic human-equivalent dose (HED) of about 10mg/kg daily almost completely prevented the cachexia in animals with advanced human colon cancer (xenograft model). The mechanism of action was, as usual, restoring NAD+ levels (and thus the NAD/NADH ratio), which are known to be drastically lower in cancer patients…as well as people with virtually any disease (including acute/infections ones). Importantly, this high(ish) dose of niacin inhibited the major NAD-consuming enzymes such as PARP-1 and CD38, both of which are elevated in cancer and, again, in virtually all known human disease, and especially in aging! Lower doses of niacin (or other NAD precursors such as niacinamide/nicotinamide, nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), etc) in the <500mg daily range may be converted more easily into NAD than higher doses (such as the one used in this study) and this lower dosing regimen may be preferable in healthier people. However, in people with severe disease and/or advanced aging, the NAD-consuming pathways dominate over the synthesis ones and the inhibition of the former (and thus preventing NAD decline) may be more important than increasing NAD synthesis by a precursor. As such, there may be a context-dependent difference in needs/doses when it comes to supplementation. In healthier people interested in general prevention the lower doses of vitamin B3 (<500mg daily) seem to work better, especially for issues such as obesity and insulin resistance. For people with more serious issues, the higher doses, as used in this study (and even higher), may be a better fit due to only higher doses inhibiting the NAD-consuming pathways. Speaking of better fit, I don’t think niacin is the optimal form of vitamin B3 for human usage. It is known to raise blood levels of both histamine and serotonin, which can be highly detrimental, especially in cancer cases. Niacinamide is, in my opinion, a better option, followed by the more commercially/pharmaceutically oriented NR, NMN, etc. However, since NMN is now banned by the FDA from OTC sales and NR is quite expensive, niacinamide is perhaps the only reasonable option.

And last but not least, I would like to point out that this study yet again discovered that in advanced cancer the levels of autophagy and AMPK are increased. Increasing both of these pathways remains one of the main goals and “selling points” of proponents of fasting, low-carb diets, endurance exercise, etc and is all-but officially endorsed by public health agencies such as FDA, CDC, USDA, etc. As I pointed out in several interviews, I don’t think it is wise to increase these pathways until we know more about them, especially given their role in cancer, and considering the fact that some of the most promising new anti-cancer drugs are autophagy inhibitors.

Vitamin B3 attenuates cancer-related muscle loss in mice
A form of vitamin B3, niacin, was found to prevent cancer-related weight loss and muscle wasting, i.e., cancer cachexia, and the underlying
http://www.miragenews.com

NAD+ repletion with niacin counteracts cancer cachexia – PubMed
Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD⁺) loss to associate…
pubmed.ncbi.nlm.nih.gov

“…Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD+) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirm that depletion of NAD+ and downregulation of Nrk2, an NAD+ biosynthetic enzyme, are common features of severe cachexia in different mouse models. Testing NAD+ repletion therapy in cachectic mice reveals that NAD+ precursor, vitamin B3 niacin, efficiently corrects tissue NAD+ levels, improves mitochondrial metabolism and ameliorates cancer- and chemotherapy-induced cachexia. In a clinical setting, we show that muscle NRK2 is downregulated in cancer patients. The low expression of NRK2 correlates with metabolic abnormalities underscoring the significance of NAD+ in the pathophysiology of human cancer cachexia. Overall, our results propose NAD+ metabolism as a therapy target for cachectic cancer patients.”

“…NRKs catalyze the utilization of NAD+ precursor NR via the salvage pathway. In the skeletal muscle, Nrk2 is the most expressed isoform in both BALB/c and C57BL/6 mouse strains as compared to Nrk1 (Supplementary Fig. 3a). Considering the Nrk2 repression in CC and the lack of a simple, translatable tool to correct Nrk2 expression, we decided to use the NAD+ booster NA, a precursor that is utilized for NAD+ biosynthesis through the Preiss-Handler pathway thus bypassing NRK218. C26-F animals were treated with a daily dose of NA (150 mg/kg) starting from day 4 after C26 implantation until day 28 (Fig. 3a). In addition to NAD+ depletion (Fig. 1a), C26-F mice presented with a significant decrease of NADH and NADPH levels while NADP+ levels were similar in comparison to controls (Supplementary Fig. 3b). Besides Nrk2 loss, C26-F mice showed an overall repression of genes involved in NAD+ biosynthesis via the salvage and Preiss-Handler pathways (Supplementary Fig. 3c) and enhanced enzyme activity of poly(ADP-ribose)polymerases (PARPs), one of the main consumers of cellular NAD+ pool operating, for example, in DNA repair (Supplementary Fig. 3d). Interestingly, NA increased skeletal muscle NAD+ and NADP+ concentrations almost to the control levels and slightly impacted on NADH and NADPH levels (Fig. 3b, Supplementary Fig. 3b). Moreover, NA supplementation improved cachexia symptoms by counteracting the loss of body weight and muscle mass and partially rescuing grasping strength (Fig. 3c–e, Supplementary Fig. 3e). Consistent with our previous report19, C26-F mice presented with decreased skeletal muscle protein synthesis, increased ratio of the active LC3B isoform (LC3B-II; Fig. 3f–h) and AMPKThr172 phosphorylation (Fig. 3f–i), suggestive of increased autophagy and energy shortage, respectively. Interestingly, both protein synthesis and LC3B-II accumulation were in part rescued by NA (Fig. 3f–h), while AMPK activation was partially prevented (Fig. 3f,i).”

 

 

 

[Lilac]

Haidut:

Cachexia Caused By Insulin Resistance
The study was done with cancer but it probably applies to other conditions involving tissue wasting. Inability to burn sugar is what caused fat and muscle tissue to waste. This also matches Ray’s views on why restricting glucose in cancer patients is pointless – i.e. the body will accelerate the rate at which it breaks down tissue in order to feed the tumor.

https://www.sciencenews.org/article/why … waste-away

“…Fat and other tissues all over the body wither in people with cancer, but the reason for the wasting, also called cachexia, was not understood. Cancer cells secrete a protein called IMPL2, researchers from Harvard Medical School and the University of California, Berkeley independently report in the April 6 Developmental Cell. Both teams came to the conclusion that the protein is responsible for wasting after giving fruit flies cancer. IMPL2 prevents healthy cells from responding to insulin, a hormone that stimulates cells to import sugar and burn it for energy. When levels of IMPL2 rise, fat, muscle and other tissues can no longer consume sugar and begin to waste away. Lowering IMPL2 levels reduces the amount of wasting, both groups found.”

[Cari]

”A diet that provides enough calcium to limit activity of the parathyroid glands, and that is low in phosphate and polyunsaturated fats, with sugar rather than starch as the main carbohydrate, possibly supplemented by niacinamide and aspirin, should help to avoid some of the degenerative processes associated with high phosphate: fatigue, heart failure, movement discoordination, hypogonadism, infertility, vascular calcification, emphysema, cancer, osteoporosis, and atrophy of skin, skeletal muscle, intestine, thymus, and spleen (Ohnishi and Razzaque, 2010; Shiraki-Iida, et al., 2000; Kuro-o, et al., 1997; Osuka and Razzaque, 2012). The foods naturally highest in phosphate, relative to calcium, are cereals, legumes, meats, and fish. Many prepared foods contain added phosphate.“ -Ray Peat

https://raypeat.com/articles/articles/phosphate-activation-aging.shtml

[J.R.K]

My prayers go out to you and your husband <span class=”atwho-inserted” contenteditable=”false” data-atwho-at-query=”@Lysa”>@lysanderswife </span>.

Many good thoughts have been posted here. A couple things come to mind. I wonder if your husband’s Vitamin D levels have been checked? It seems that in review of those that had their cancers go into remission from chemotherapy and those that did not the Vitamin D levels were high in those that achieved remission and low in those that did not.
Haidut also mentioned Dr Peats observation on high dose Aspirin up to four grams per day if memory serves. I would of course recommend Vitamin K2 to mitigate any bleeding that might accompany this high of a dosage of Aspirin.

Haidut also had done some experiments with his product Pyrucet. He mentioned a woman in Bulgaria with terminal stage four glioblastoma. Providing pyruvate to the cells seemed to help possibly dedifferentiate the cancer cells in question back to healthy cells. The story goes that she was sent home and was able to return to work. This might be something worth taking the time to research.

At the risk of sounding redundant  eliminating any and all PUFA would be a first priority. But starting at the basics first, and trying to restore oxidative phosphorylation and eliminating the blockage in the electron transport chain to help restore optimal mitochondrial function, and quieting the call for cortisol and gluconeogenesis that is at the heart of cachexia.

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