Arachidonic acid, 5-HETE, ginger, CLA, and prostate cancer;

Breast cancer may be similar. Chicken? yes or no? or it depends on cooking method?

I reread a 2012 post of mine about prostate cancer and arachidonic acid and decided to look for research updates regarding my speculation about a study published online in 2011 by Schumacher, et al., 2013. It suggested that dietary fats were affecting benign or malignant prostate cancer tumors, from the same person/same prostate, differently. Arachidonic acid was elevated but total omega 6 fatty acids were reduced in the malignant tumors, except for a precursor omega 6 that can be made into others. Was the idea that omega 3 fatty acids are protective wrong? Or was the research team’s interpretation that dietary fats were involved wrong?

Arachidonic acid is rich in chicken broth, long-cooked meats have more freed from cell membrane breakdown and eggs are a source.

Arachidonic acid is also freed from our own cell membranes in response to inflammatory signaling of increased calcium levels. The calcium inside of a cell causes endocannabinoids to be released from membranes and the phospho- end and the lipid- end may be separated as the endocannabinoid is made into eicosanoids. Prostaglandins (PGs) and leukotrienes (LTs) are two types of eicosanoids. That leaves a lot of arachidonic acid floating around or ethanolamine, another type of lipid that might be used in endocannabinoids.

If there is far more arachidonic acid in malignant tumor cells than benign tumor cells than I don’t think it is because the same human eating the same diet is sending more arachidonic acid exclusively to malignant tumor cells. I think it is being formed there in response to inflammation.

Fast forwarding to 2016 - yes, dietary fats do not seem to play a direct role in the difference seen in prostate cancer cells. The research team of Cui, et al., 2016 looked at genetic differences as their theory regarding the elevated arachidonic acid in prostate cancer and found some slight differences in one of the enzymes that can be used to form longer omega3 or 6 fatty acids from shorter plant or animal lipids. Their theory seems to be that some people make too much of the arachidonic acid from other dietary fats endogenously - internally, rather than having a difference in dietary intake. Dietary fat intake was not found to correlate with the lipid ratios seen in prostate cancer. (Cui, et al., 2016)

Stuff I had in my 2012 post, coincidentally, or causally, prostate cancer cells can turn arachidonic acid into 5-HETE which they can then use as a food source (along with glutamates). (Karna, et al., 2012)

Excerpt from my 2012 post: “Elsewhere information has been discovered that malignant prostate cancer cells can make an enzyme that can convert Arachidonic acid into a form usable as a food source for the malignant growth. Increased intake of CLA and ginger may help preserve arachidonic acid from being converted to 5-HETE which the cancer cells can use as an energy source. (Karna, et al., 2012) (Ginger slows prostate cancer growth,10/20/2011) So targeting the enzyme that converts AA to 5-HETE would make more sense than wondering what omega 6 and omega 3 ratio on the person's plate might turn malignant cells back into benign ones.” (*or vice versa.)

And fast forwarding to 2017, it turns out there is endocannabinoid dysregulation in prostate cancer. (Karlsson, et al., 2017)

“Tumour necrosis factor α (TNFα) is involved in the pathogenesis of prostate cancer, a disease where disturbances in the endocannabinoid system are seen.” (Karlsson, et al., 2017)

The team tested whether prostate tumor cell uptake of anandamide (AEA) (*the THC equivalent endocannabinoid) might be affected by treatment with TNFalpha (an inflammatory protein that is part of NFkB pathways). The control group were a type of macrophage cells (white blood cells). The team found that the level of an enzyme used to make AEA was decreased in the prostate cancer cells after TNFalpha treatment compared to the macrophage cells. COX2 inhibition did not affect anandamide uptake while the AEA hydrolytic enzyme fatty acid amide hydrolase (FAAH) did increase uptake of AEA in both types of cells. FAAH was one of the enzymes whose levels did not change with TNFalpha treatment. (Karlsson, et al., 2017)

“TNFα treatment of DU145 cells increased mRNA levels of PTSG2 (gene of COX-2) and decreased the mRNA of the AEA synthetic enzyme N-acyl-phosphatidylethanolamine selective phospholipase D. mRNA levels of the AEA hydrolytic enzymes fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing acid amidase were not changed.” (Karlsson, et al., 2017)

What the team also found was that prostaglandins were only present after the cells were preincubated with anandamide.

“AEA and related NAEs were detected in DU145 cells, but PGs and PGE₂-EA were only detected when the cells had been preincubated with 100 nM AEA.” (Karlsson, et al., 2017)

They suggest more research is needed into the endocannabinoid differences seen in prostate cancer - I would suggest reading more about the endocannabinoid system and eicosanoids. The anandamide had to already be in the cell for prostaglandins to be present - per team’s results. (Karlsson, et al., 2017) For prostaglandins to be present from the anandamide precursor, then arachidonic acid would end up being present too (which was not measured in this study) after the eicosanoids were made from the anandamide.

Fresh Ginger Root. Photo by Mitchell Luo on Unsplash

Excerpt from my 2011 post: “Two grams of ginger per day for one month time periods was found successful at reducing inflammation of the intestinal lining in human studies. [5,6] Free arachidonic acid levels were reduced. Arachidonic acid levels are typically increased in inflammation and it has been found to be a precursor for 5-HETE, a main energy source for stimulating prostate cancer cell growth. [8-12] The prostate cancer cells seem to have the ability to increase production of  an enzyme that converts arachidonic acid (half of the endogenous cannabinoid, anandamide) into 5-HETE which is a form needed by the cancer cells.

Conjugated linolenic acid (CLA) was used successfully to reduce breast tumor growth in a study regarding the same enzyme from the prostate cancer cells, 5-lipoxygenase (5-LO). The CLA, an essential fatty acid, was not found to be inhibiting the 5-LO enzyme but instead it was reducing the enzyme’s activating protein and possibly competing with arachidonic acid (also an essential fatty acid). It might be able to stand in for the 5-LO enzyme but less 5-HETE was being produced and breast tumor cell growth was “attenuated” (sounds like a good thing).”

Attenuation can be defined as the process by which a virus, bacterium, etc., changes under laboratory conditions to become harmless or less virulent.

• To cut to the chase - my tip is to try to reduce stress/inflammation. Inflammatory signaling causes TNFalpha to cause excess intracellular calcium which causes release of anandamide from the cell membrane, which then may be made into prostaglandins and arachidonic acid.

• Also, eat more ginger* to prevent the conversion of arachidonic acid into 5-HETE by prostate cancer cells. (Karna, et al., 2012) *Caution: Ginger root is a TRP channel activator that can make histamine problems worse, and it is high in salicylates.

• And more CLA fatty acid may help by reducing activity of the 5-LO enzyme on conversion of arachidonic acid into 5-HETE.

• Reducing any stressors in life would help as the TNFalpha is part of the inflammatory stress or active day circadian pathways. So, healing your circadian cycle and sleep would also be protective.

Also, maybe do avoid rich sources of arachidonic acid in the diet as it might also feed prostate or breast cancer cells after being converted to 5-HETE by them.

• The research and meta-reviews mashing together Western, Mexican and South Asian groups found chicken intake doesn’t seem to effect prostate cancer risk. However, the one citation mentioned as finding a strong correlation with Western diet poultry use and prostate cancer seems to be gone from the internet, yet the Wayback Machine says it is still a working URL.

“Meat attracted nutritionists’ concern for hazardous component. Researchers have found that meat cooked in high temperature contained considerable amount of mutagens. The hazardous component evoked the hypothesis that meat consumption would be in positive association with elevated PCa risk. Red meat and processed meat were proved to support the hypothesis and lower consumption was thus recommended (Mandair et al., 2014). The role of poultry, counterpart of red meat, has also been evaluated in a number of studies, but the evidence was inconclusive. For one thing, some studies was in favor of the hypothesis. Stott-Miller and colleagues’ (2013) study on fried chicken demonstrated that fried chicken would place individuals at heightened risk of [Prostate Cancer] PCa. Also statistics of the United States revealed strong positive correlation between PCa mortality and per capita consumption of chicken (Colli & Colli, 2005). There was also study claiming decreased risk when high amount of poultry intake compared with low intake (Hu et al., 2008). However, a large number of studies observed null association between them. A substitution model and addition model in a cohort study also failed to obtain statistically significant relationship (Daniel et al., 2011a).” (He, et al., 2016)

Meta-reviews = mushy data that becomes kind of meaningless, to me. How was the chicken cooked? We know in the fried chicken study. (Stott-Miller, et al., 2013) We wouldn’t know in most survey-based studies.

It likely would be unclear whether ‘poultry’ or ‘chicken’ causes cancer more than other foods, as the cooking method would likely count beyond crispy fried chicken (AGEs - look it up).

Not all chicken products would have the same arachidonic acid content. A slow cooked broth made with the carcass would have a much higher amount than a drier cooking method like chicken stir-fry. Arachidonic acid is released from the membranes as the endocannabinoids are broken down. Chicken prepared with more skin and gristly bits would have more. And if the poultry is cooked with a broth or steam, more softening occurs, and more membrane breakdown is part of that softer texture.

Beef, marbled meat, high saturated fat, is going to be more inflammatory and research shows a cancer association with red meat. Barbecue blackened would be higher cancer risk yet because of the acrylamide and other AGEs tasty sugar protein chemicals that are formed under higher heat when sugar is present.

Anecdotal - My mom has a mass under one breast and is losing weight but with her Alzheimer’s we are not seeking special diagnosis (*it’s probably a three-CoV-jab variety) or standard cancer care. She liked chicken and it is easy to use the Broaster chicken from grocery deli’s. I had initially gone to a lot of trouble to only prepare fresh foods for my parents, but my dad didn’t really like it and it is a lot of work to make food for picky eaters which I can’t also eat. It goes to waste. I have stopped using chicken for her. She needs puree now anyway and pureed meat is kind of yucky, I had tried it before finding the mass. We are still using eggs, soft texture. Egg yolk has anti-CoV benefits. Broaster chicken probably has a lot of other chemical negatives besides arachidonic acid too.

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I had five four posts on this topic - prostate cancer or breast cancer and 5-HETE, arachidonic acid, calcium excess, CLA, and ginger. My blog format style has improved over time.

• Eicosanoids are made from eCBs from the membrane, Oct, 4, 2011.

• Ginger slows prostate cancer growth, Oct. 21, 2011.

• Prostate and breast cancer and omega 6s and 3s, May 16, 2012

• A research study proposal; for clarity Nov 11, 2015.

Salicylates - a new page on this site.

• Carrots, spices and baby aspirin help prevent cancer and inflammation, Oct. 21, 2011. *this one is about salicylates actually. And - deNutrients news to use - I added a page on Salicylate Risks/benefits; Fibromyalgia and POTS, (SubStack page) ← they seem related, can be comorbid and salicylate excess may be causal in both. I wander from the main point, pretty often. Histone acetylation may be reduced due to salicylate excess and that leads to underactivity of a gene. POTS has an underactive expression of a norepinephrine transport protein needed for reuptake of norepinephrine. (Khan, et al., 2017)

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of Fair Use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a *functional health professional for individual health care purposes.

Reference List

(Cui, et al., 2016) Cui T, Hester AG, Seeds MC, Rahbar E, Howard TD, Sergeant S, Chilton FH. Impact of Genetic and Epigenetic Variations Within the FADS Cluster on the Composition and Metabolism of Polyunsaturated Fatty Acids in Prostate Cancer. Prostate. 2016 Sep;76(13):1182-91. doi: 10.1002/pros.23205. Epub 2016 May 16. PMID: 27197070; PMCID: PMC6680327. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680327/

(He, et al., 2016) He Q, Wan ZC, Xu XB, Wu J, Xiong GL. Poultry consumption and prostate cancer risk: a meta-analysis. PeerJ. 2016 Feb 2;4:e1646. doi: 10.7717/peerj.1646. PMID: 26855875; PMCID: PMC4741082. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741082/

(Karlsson, et al., 2017) Karlsson J, Gouveia-Figueira S, Alhouayek M, Fowler CJ (2017) Effects of tumour necrosis factor α upon the metabolism of the endocannabinoid anandamide in prostate cancer cells. PLoS ONE 12(9): e0185011. https://doi.org/10.1371/journal.pone.0185011 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185011

(Karna, et al., 2012) Karna P, Chagani S, Gundala SR, Rida PC, Asif G, Sharma V, Gupta MV, Aneja R. Benefits of whole ginger extract in prostate cancer. Br J Nutr. 2012 Feb;107(4):473-84. doi: 10.1017/S0007114511003308. Epub 2011 Aug 18. PMID: 21849094; PMCID: PMC3426621. https://pubmed.ncbi.nlm.nih.gov/21849094/

(Schumacher, et al., 2013) Schumacher MC, Laven B, Petersson F, Cederholm T, Onelöv E, Ekman P, Brendler C. A comparative study of tissue ω-6 and ω-3 polyunsaturated fatty acids (PUFA) in benign and malignant pathologic stage pT2a radical prostatectomy specimens. Urol Oncol. 2013 Apr;31(3):318-24. doi: 10.1016/j.urolonc.2011.01.014. Epub 2011 Apr 1. PMID: 21414816. https://pubmed.ncbi.nlm.nih.gov/21414816/

(Zick, et al., 2011) Zick SM, Turgeon DK, Vareed SK, Ruffin MT, Litzinger AJ, Wright BD, Alrawi S, Normolle DP, Djuric Z, Brenner DE. Phase II study of the effects of ginger root extract on eicosanoids in colon mucosa in people at normal risk for colorectal cancer. Cancer Prev Res (Phila). 2011 Nov;4(11):1929-37. doi: 10.1158/1940-6207.CAPR-11-0224. Epub 2011 Oct 11. PMID: 21990307; PMCID: PMC3208778. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208778/