PUFAs Poison The Pancreas
The idea that sugar causes the pancreatic diseases – although popular – is unscientific and unsubstantiated. Meanwhile, experiments have shown that exposure to polyunsaturated fatty acids (PUFAs), can promote inflammation, pancreatitis, and the growth and spread of pancreatic cancer.
“The involvement of…liberated fatty acids in ethiology of acute pancreatitis (AP) has been implicated…ratio of saturated to polyunsaturated fatty acids was significantly lower than in control group…Polyunsaturated fatty acids, mainly linoleic and arachidonic, may be involved in the development of complications in acute pancreatitis.”
“…different serum FFA [free fatty acid] compositions in patients with AP [acute pancreatitis] were related to the severity and complications of AP. Unsaturated fatty acids, mainly linoleic acid, may be involved in the development of complications of AP…”
Cholecystokinin (CCK) is a gastrointestinal hormone that has been demonstrated to play a role in the development and spread of pancreatic cancer. CCK release has been shown to be stimulated by the consumption of a high fat diet.
“The gastrointestinal peptide cholecystokinin (CCK) is released…in response to dietary fat to aid in digestion…plasma CCK levels are elevated with the consumption of high fat diets…CCK…has…been shown to stimulate growth of pancreatic cancer…The high fat diet [lard] significantly increased growth and metastasis of pancreatic cancer…”
“In human pancreatic cancers, CCK receptors are ubiquitous and over-expressed and activation of these receptors with CCK or its related peptide gastrin, stimulate tumor growth…it may be possible to use CCK receptor antagonists as a chemopreventive treatment for those patients who are at high risk for pancreatic cancer…”
Studies have demonstrated that the unsaturated fats more strongly stimulate CCK release than the saturated fats, and this may in part explain their carcinogenic effect.
The monounsaturated oleic acid (the main fatty acid in olive oil) promotes CCK release at a rate slightly slower than the polyunsaturated fats (like sunflower or safflower oil), however it is still a far more powerful stimulant of the release of CCK, than is saturated fat.
“The…monounsaturated fatty acid oleic acid…produced a significantly greater integrated CCK response than that of the saturated fatty acid stearic acid…The finding that unsaturated fats are stronger stimulants of CCK release than saturated fats may explain the promotion of pancreatic carcinogenesis in rats by unsaturated but not saturated fats and may support the role of CCK in this effect.”
Cancer is an inflammatory disease which has been shown to be driven (at least in part), by chronic exposure to stress. Pancreatic cancer is associated with increased levels of a variety of stress substances including cortisol, adrenalin, and the inflammatory, diabetogenic PUFAs. Prolonged stress (and ongoing inflammatory stress substance release), can interfere with insulin function, and encourage pancreatic disease in general.
“Psychological stress significantly promoted xenograft growth and increased systemic and tumor levels of noradrenalin, adrenalin, cortisol, VEGF and cAMP while GABA and GAD were suppressed…Our data show…that neurotransmitter responses to psychological stress significantly induced multiple signaling pathways that regulate the proliferation, migration, angiogenesis and apoptosis of pancreatic cancer, resulting in a significant promotion of tumor growth…”
Inflammation promotes chronic pancreatitis, and pancreatitis is a condition which very often precedes pancreatic cancer.
“Chronic pancreatitis…is considered to be the single most important cause for development of pancreatic cancer…evidence suggests that inflammation and oxidative stress play pivotal roles in the development of…conditions like pancreatitis.”
The breakdown products of the PUFAs (like malondialdehyde and 4-HNE) are implicated with the promotion of oxidative stress, and both PUFA degradation and oxidative stress are involved in the etiology of inflammation. Oxidative stress has been shown to play an important part in the progression of pancreatitis.
“In chronic pancreatitis, conjugated dienes as well as malondialdehyde concentrations in the tissue were significantly elevated. Reduced glutathione was significantly decreased, suggesting glutathione depletion due to oxidative stress…the increased tissue levels of lipid peroxidation products and the changes in glutathione metabolism suggest ongoing peroxidation of lipids due to an enhanced generation of oxygen radicals.”
“Levels of malondialdehyde were raised in acute pancreatitis patients and increased in patients with severe compared with mild acute pancreatitis…Plasma malondialdehyde may be a helpful additional marker of severity in the very early stages of acute pancreatitis.”
“The significantly increased plasma levels of MDA, 4-HNE, and nitrites indicate that oxidative stress is present in patients with CP [chronic pancreatitis] and that it may play a role in initiation and maintenance of inflammation within the pancreatic tissue in CP patients.”
“…study provides…evidence showing a link between oxidative stress and clinical disease severity of acute pancreatitis. Key indicators of oxidative stress…and secondary products of lipid peroxidation increased or altered notably during the course of acute pancreatitis, and these changes were sustained for longer than the clinical manifestation of illness.”
The promotion and exacerbation of chronic inflammation and oxidative stress due to PUFA consumption and breakdown, can also be seen to be a factor leading to the development and metastasis of pancreatic cancer.
“The link between inflammation and pancreatic cancer has been observed for a number of gastrointestinal neoplasms. This review examines the role of inflammation in pancreatic carcinogenesis…Sustained damage caused by chronic inflammation may precede the onset of frank malignancy by a significant interval…suppression of inflammatory changes and oxidative damage, may help delay or even prevent the inception of pancreatic neoplasia.”
“Chronic inflammation is a well-documented risk for carcinogenesis, particularly in the pancreas and gastrointestinal tract…Chronic pancreatitis involves long-standing inflammation of the pancreas associated with an increased risk (˜20 folds) for pancreatic cancer.”
“Intake of ω-6 polyunsaturated fatty acids provides increased substrate for COX and LOX mediated metabolism of arachidonic acid into eicosanoids. These eicosanoids directly contribute to pancreatic cancer cell proliferation.”
Chronic stress, or anything that interferes with thyroid energy metabolism and digestive function, increases bacterial issues, causing greater exposure to bacterial endotoxin. Endotoxin is a powerful independent promoter of inflammation.
PUFA consumption suppresses metabolism and digestion, and interacts with circulating bacterial endotoxin (LPS). The inflammatory effects of PUFA and endotoxin have been demonstrated to encourage pancreatitis and the onset and metastasis of cancer of the pancreas.
“LPS induced pancreatic damage by directly affecting the pancreatic acinar cells. The role of LPS in the pathophysiology of acute pancreatitis may be partly due to the effect LPS has on the acinar cell.”
“Inflammation plays a multifaceted role in cancer progression, and NF-kappaB is one of the key factors connecting inflammation with cancer progression. We have shown that lipopolysaccharide (LPS) promotes NF-kappaB activation in colon cancer cells and pancreatic cancer cells…LPS increased the invasive ability of pancreatic cancer cells.”
Bacterial endotoxin exposure directly promotes an increase in the release of serotonin. Serotonin has been shown to play a role in the development of pancreatitis, as well as many kinds of cancer.
“The aim of the present study was to elucidate the pathogenic role of endogenous 5-HT in pancreatitis…results suggest that endogenously released 5-HT [serotonin] aggravate[s]…pancreatitis…selective 5-HT2A antagonists may provide a new therapy for acute pancreatitis.”
Stress, PUFAs, inflammation, metabolic suppression and endotoxin exposure, also increase nitric oxide (NO) levels (which further promote stress and interfere with energy metabolism), and NO has been shown to be involved in the growth and spread of cancer, including pancreatic cancer.
“Pancreatic ductal adenocarcinoma (PDAC) expresses high level of inducible nitric oxide synthase (NOS2), which causes sustained production of nitric oxide (NO)…Enhanced NOS2 expression in tumors significantly associated with poor survival in PDAC patients…NOS2 is a predictor of prognosis in early stage, resected PDAC patients, and provide proof-of-principle that targeting NOS2 may have potential therapeutic value in this lethal malignancy.”
“Association of a higher expression of NOS2 [inducible NO] with poorer survival in a large cohort of patients with multiple validations in independent cohorts suggests a role of NO• in pancreatic cancer progression and disease aggressiveness.”
“…overproduction of NO imposes an adverse selection pressure on the tumor microenvironment, which causes genetic and epigenetic changes in tumor…and promotes the evolution of these cells into more malignant cells conferred with a tremendous survival and growth advantage…”
The inflammatory stress promoting effects of PUFA exposure, interfere with the role of blood sugar in metabolic energy production. Many stress related things that occur as a result of the suppression of metabolism (such as hypoxia and increased lactate production) are directly involved in the progression of the cancer metabolism, and the development of pancreatic cancer.
“…the Warburg Effect has been long been recognised to occur in cancer cells, and describes a “metabolic switch” in the way cells use glucose to produce ATP. This overview highlights the extensive changes that in PDAC [pancreatic ductal adenocarcinoma]…produce a distinct metabolic phenotype.”
“Lactate dehydrogenase A (LDHA) executes the final step of aerobic glycolysis and has been reported to be involved in the tumor progression…the expression of LDHA was elevated in the clinical pancreatic cancer…Forced expression of LDHA promoted the growth of pancreatic cancer cells, while knocking down the expression of LDHA inhibited cell growth dramatically.”
“Pancreatic cancer is a highly deadly disease: almost all patients develop metastases and conventional treatments have little impact…chemoresistance is…linked to specific metabolic aberrations of pancreatic cancer cells…The main consequence of metabolic reprogramming is to provide energy and building blocks to tumor cells for proliferation…cancer cells acidify their microenvironment by promoting glycolysis…enhancing tumor metastatic potential…A high glycolysis rate leads to more lactate production, which can stimulates angiogenesis and functions…to take over the limited energy availability…”
“…results demonstrate that hypoxia-driven metabolic adaptive processes, such as high glycolytic rate…favor hypoxic and normoxic cancer cell survival and correlate with pancreatic ductal adenocarcinoma aggressiveness.”
Sugar restriction promotes stress and the increase in release of PUFAs out of storage, promoting the stress substances (including cortisol, endotoxin, serotonin, nitric oxide and others) all of which can help create an inflamed, hypoxic, blood sugar dysregulated state which can lead to pancreatitis and pancreatic cancer.
Sugar protects against stress and polyunsaturated free fatty acid release, helping thyroid metabolism to function better. Stress, inflammation, PUFAs and interference with mitochondrial energy production, are intimately connected to thyroid function, and improved thyroid function has been demonstrated to protect against the progression of pancreatic cancer.
“T3 groups showed significantly reduced tumor volume and weight…Thyroid hormone can inhibit the growth of human pancreatic cancer…suppressing the proliferation and angiogenesis of the tumor cells, suggesting the potential value of thyroid hormone in pancreatic cancer therapy.”
PUFAs, sugar restriction, and all the things that increase stress and interfere with blood sugar utilization and thyroid energy production, also promote obesity and diabetes, and the relationship between these issues (and other metabolic illnesses) and pancreatic disease is not coincidental.
“Increasing evidence suggests that patients with certain types of cancer…who also have diabetes or impaired glucose tolerance are at increased risk for cancer recurrence, cancer-related death, and death due to any cause…hormonal or metabolic abnormalities, such as hyperinsulinemia and hyperglycemia, affect tumor biology at multiple stages, including malignant transformation, growth, and metastasis…new therapeutic regimens targeting energy metabolism or inflammation…and modulation of lipid metabolism may hold great promise in the treatment of pancreatic cancer, especially that associated with diabetes and obesity…”
Avoiding PUFAs and too much of the digestion interfering grains, beans, nuts and fibrous foods, and including sufficient amounts of easy to assimilate protein and sugar (from sweet ripe fruits, fruit juice, milk, honey and white sugar) is one potential way to help protect against pancreatic cancer and pancreatic disease in general.
Some other things which can be protective against pancreatitis and pancreatic cancer include aspirin, niacinamide, a few kinds of antibiotics, emodin, sodium bicarb and a variety of pro-metabolic, thyroid supportive, stress reducing, anti-inflammatory things.
With so much press claiming to expose the dangers of sugar consumption when it comes to cancer (and diabetes and inflammatory illness in general), it’s easy to assume that sugar is to blame.
I’m not a doctor or a scientist, but it looks to me like it’s always blood sugar dysregulation that is interlinked with stress and inflammation and disease progression, and when you look closely you can see that it isn’t sugar, but other things which are responsible for that. PUFAs are one of the main culprits.
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Increased expression of inducible nitric oxide synthase (iNOS) in N -nitrosobis(2-oxopropyl)amine-induced hamster pancreatic carcinogenesis and prevention of cancer development by ONO-1714, an iNOS inhibitor