PUFA Promote Cancer

Also see:
Toxicity of Stored PUFA
Dietary PUFA Reflected in Human Subcutaneous Fat Tissue
PUFA Accumulation & Aging
Maternal PUFA Intake Increases Breast Cancer Risk in Female Offspring
Israeli Paradox: High Omega -6 Diet Promotes Disease
Benefits of Aspirin
Arachidonic Acid’s Role in Stress and Shock
Most cancer cases due to lifestyle choices, not ‘bad luck,’ study suggests

“After presenting overwhelming evidence that thyroid deficiency is the culprit in antherosclerosis, the final chapter urges the abandonment of polyunsaturated fats in our diet. In both experimental animals and man, in addition to toxic symptoms, a rise in cancer has been reported after prolonged ingestion of polyunsaturated fats.” -Broda Barnes, MD, PhD (Solved the Riddle of Heart Attacks)

“Be very careful with the unsaturated oils, such as safflower, corn, and cod liver oil: they destroy vitamin E and can cause cancer.” -Ray Peat, PhD

“In 1927, German researchers reported that a fat-free diet prevented the occurrence of spontaneous cancers in rats . Since, a little later, other workers found that the elimination of unsaturated fats from the diet not only prevented cancer, but also caused a large increase in the metabolic rate, it might have been possible to conclude that it is not living which kills us, but something in the environment. Some people did draw that conclusion, but research funds go mainly to product-oriented research, and “the environment” has been hard to package as a product.” -Ray Peat, PhD

“Cancer can’t occur, unless there are unsaturated oils in the diet. [C. Ip, et al., Cancer Res. 45, 1985.]” -Ray Peat, PhD

“The absence of cancer on a diet lacking unsaturated fats, the increased rate of metabolism, decreased free radical production, resistance to stress and poisoning by iron, alcohol, endotoxin, alloxan and streptozotocin, etc., improvement of brain structure and function, decreased susceptibility to blood clots, and lack of obesity and age pigment on a diet using coconut oil rather than unsaturated fats, indicates that something very simple can be done to reduce the suffering from the major degenerative diseases, and that it is very likely acting by reducing the aging process itself at its physiological core.” -Ray Peat, PhD

“There are many people currently recommending fish oil (or other highly unsaturated oils) for preventing or treating cancer, and it has become almost as common to recommend a sugar free diet, “because sugar feeds cancer.” This is often, incorrectly, said to be the meaning of Warburg’s demonstration that cancer cells have a respiratory defect that causes them to produce lactic acid from glucose even in the presence of oxygen. Cancer cells use glucose and the amino acid glutamine primarily for synthetic purposes, and use fats as their energy source;the growth stimulating effect of the “essential fatty acids” (Sueyoshi and Nagao, 1962a; Holley, et al., 1974) shows that depriving a tumor of those fats retards its growth. The great energetic inefficiency of the cancer metabolism, which causes it to produce a large amount of heat and to cause systemic stress, failure of immunity, and weight loss, is because it synthesizes fat from glucose and amino acids, and then oxidizes the fat as if it were diabetic.” -Ray Peat, PhD

“If the cancer-productive field is taken into account, all of the factors that promote and sustain that field should be considered during therapy.

Two ubiquitous carcinogenic factors that can be manipulated without toxins are the polyunsaturated fatty acids (PUFA) and estrogen. These closely interact with each other, and there are many ways in which they can be modulated.

For example, keeping cells in a well oxygenated state with thyroid hormone and carbon dioxide will shift the balance from estradiol toward the weaker estrone. The thyroid stimulation will cause the liver to excrete estrogen more quickly, and will help to prevent the formation of aromatase in the tissues. Low temperature is one of the factors that increases the formation of estrogen. Lactic acid, serotonin, nitric oxide, prostaglandins, and the endorphins will be decreased by the shift toward efficient oxidative metabolism.

Progesterone synthesis will be increased by the higher metabolic rate, and will tend to keep the temperature higher.

Thyroid hormone, by causing a shift away from estrogen and serotonin, lowers prolactin, which is involved in the promotion of several kinds of cancer.

Vitamin D and vitamin K have some antiestrogenic effects. Vitamin D and calcium lower the inflammation-promoting parathyroid hormone (PTH).

Eliminating polyunsaturated fats from the diet is essential if the bystander effect is eventually to be restrained. Aspirin and salicylic acid can block many of the carcinogenic effects of the PUFA. Saturated fats have a variety of antiinflammatory and anticancer actions. Some of those effects are direct, others are the result of blocking the toxic effects of the PUFA. Keeping the stored unsaturated fats from circulating in the blood is helpful, since it takes years to eliminate them from the tissues after the diet has changed. Niacinamide inhibits lipolysis. Avoiding over-production of lipolytic adrenaline requires adequate thyroid hormone, and the adjustment of the diet to minimize fluctuations of blood sugar.” -Ray Peat, PhD

Cancer Res. 1985 May;45(5):1997-2001.
Requirement of essential fatty acid for mammary tumorigenesis in the rat.
Ip C, Carter CA, Ip MM.
In an attempt to determine the requirement of essential fatty acid for dimethylbenz(a)anthracene-induced mammary tumorigenesis, rats were fed diets containing different levels of linoleate: 0.5, 1.1, 1.7, 2.2, 3.5, 4.4, 8.5, or 11.5%. Each diet contained 20% of fat by weight, with varying amounts of coconut oil and corn oil added to achieve the desired levels of linoleate. Mammary tumorigenesis was very sensitive to linoleate intake and increased proportionately in the range of 0.5 to 4.4% of dietary linoleate. Regression analysis indicated that a breakpoint occurred at 4.4%, beyond which there was a very poor linear relationship, suggesting the possibility of a plateau. From the intersection of the regression lines in both the upper and lower ranges, the level of linoleate required to elicit the maximal tumorigenic response was estimated to be around 4%. The differences in tumor yield could not be correlated with changes in prostaglandin E concentration in the mammary fat pads of normal animals maintained on similar diets, suggesting that linoleate may act by some other mechanism to stimulate mammary tumorigenesis.

Nutrition Research
Volume 12, Issue 6, June 1992, Pages 767-772
Effect of low level flaxseed suplementation on the fatty acid composition of mammary glands and tumors in rats
Maria R. Serraino Ph.D., Lilian U. Thompson Ph.D., Stephen C. Cunnane Ph.D.
The high alpha-linolenic acid (ALA; C18:3n-3) content of flaxseed oil and the observed protective effects of omega-3 fatty acids on cancer have led to the hypothesis that the fatty acid composition of flaxseed may render it protective against cancer. Previous studies have suggested that supplementation of a basal high-fat diet with flaxseed flour (FF) at the 5% level may influence the risk for mammary carcinogenesis but it is unknown whether the fatty acid composition of its oil (1.9% in the diet) contributed to this effect. This study showed that feeding 5% FF significantly increased the ALA and decreased the C22:5n-6 contents of the mammary glands and tumors of carcinogen-treated rats and the mammary gland of the non-carcinogen treated rats. There were small but insignificant effects on the endogenously synthesized long chain fatty acids (e.g. 16:0, 16:1n-7, 18:0 and 18:1n-9) and the longer chain unsaturated fatty acids (e.g. 20:5n-3 and 22:6n-3) derived as a result of chain elongation and desaturation of ALA. The results suggest that the fatty acid composition of the mammary tissues and tumors may be affected even at low level of flaxseed oil, and that this oil may have a role in the observed effect of flaxseed on tumorigenesis. Further studies are required to explore this possibility.

In Vivo. 1998 Nov-Dec;12(6):675-89.
Comparative anticancer effects of vaccination and dietary factors on experimentally-induced cancers.
Zusman I.
The role of two major factors were analyzed in the prevention of experimentally-induced cancers: a) vaccination of animals with polyclonal IgG generated against the soluble p53 antigen and b) feeding of animals with diets rich with dietary fibers or fat. a) In vaccination, a few attempts have been made to utilize p53 protein as a tumor suppressor. IgG generated against the cytoplasmic, soluble p53 antigen from tumor-bearing rats prevents the carcinogenic effect of 1,2-dimethylhydrazine (DMH) decreasing significantly the number of tumor-bearing rats in vaccinated group compared with non vaccinated controls and preventing benign tumors from becoming malignant. The antitumor effect of vaccination is accompanied by a significant increase in the serum-level of p53 antigen in vaccinated rats compared with non vaccinated controls. The immune response of a host to vaccination activates the lymph components of the spleen, and this activation is manifested by the multiplication of the number of lymphocytes which are generated against specific antigens. This multiplication is achieved by the higher division of the antigen-specific lymphoblasts with their subsequent transformation into plasma cells. These cells synthesize the specific protein (IgG). One such protein is the tumor-associated p53 protein, which is synthesized by rats against rabbit anti-p53 IgG. b) The role of dietary factors in the prevention of chemically induced cancer was reviewed on two models: the role of high fiber diets in prevention of colon cancer, and the role of high fat diets in the prevention of mammary gland cancer. Experiments in colon cancer showed that 20% cellulose decreased significantly tumor incidence caused by DMH. The tumor-preventive effect of a cellulose diet was accompanied by increased enzyme concentrations, such as ornithine decarboxylase, thymidine kinase and beta-glucuronidase. This effect was accompanied by activation of some cellular mechanisms, i.e. apoptosis, proliferating cell nuclear antigen (PCNA) and p53 protein synthesis. Experiments in mammary glands cancer showed that a 15% olive-oil diet reduced significantly the tumor incidence caused by 9,10-dimethyl-1,2-benzanthracene. The antitumor effect of the olive-oil diet was connected to its content of monounsaturated fatty acids, such as oleic and palmitic acids. The promotive tumorigenic effects of other high-fat diets (avocado, soybeans) were associated with high content of some polyunsaturated fatty acids (linoleic and alpha-linolenic). Different diets have different targets. The effect of the same diet depends on its anti-tumor substances content. CONCLUSIONS: Vaccination and some diets have similar mechanism in their tumor-preventive effects.

Am J Clin Nutr. 1991 Apr;53(4 Suppl):1064S-1067S.
Dietary fats and cancer.
Carroll KK.
Evidence relating dietary fat to cancer at sites such as the breast and colon is provided by experiments showing that animals fed high-fat diets develop cancer at these sites more readily than do animals fed low-fat diets and by epidemiological data from different countries showing strong positive correlations between cancer incidence and mortality, and level of dietary fat. Experiments on animals have indicated that polyunsaturated vegetable oils promote cancer more effectively than do saturated fats or polyunsaturated fish oils, whereas in the epidemiological data, total dietary fat correlates with cancer incidence and mortality at least as well as does any particular type of fat. Case-control and cohort studies have not shown strong indications of a relationship between dietary fat and cancer, perhaps because of methodological difficulties inherent in such studies. The weight of evidence continues to indicate that long-term adherence to a low-fat diet can reduce the risk of some common types of cancer.

Cancer Res. 1998 Aug 1;58(15):3312-9.
Dietary omega-3 polyunsaturated fatty acids promote colon carcinoma metastasis in rat liver.
Griffini P, Fehres O, Klieverik L, Vogels IM, Tigchelaar W, Smorenburg SM, Van Noorden CJ.
The effects of omega-3 polyunsaturated fatty acids (PUFAs) and omega-6 PUFAs on the development of experimentally induced colon carcinoma metastasis in rat liver were investigated quantitatively in vivo. Rats were kept on either a low-fat diet or on a fish oil (omega-3 PUFAs) or safflower oil (omega-6 PUFAs) diet for 3 weeks before the administration of colon cancer cells to the portal vein, until they were sacrificed at 1 or 3 weeks after tumor transplantation. At 1 week after transplantation, the fish oil diet had induced 7-fold more metastases (in terms of number and size) than had the low-fat diet, whereas the safflower oil diet had not affected the number and total volume of metastases. At 3 weeks after tumor transplantation, the fish oil diet and the safflower oil diet had induced, respectively, 10- and 4-fold more metastases (number) and over 1000- and 500-fold more metastases (size) than were found in the livers of rats on the low-fat diet. These differences were sex independent. Immunohistochemical analysis revealed that the immune system in the liver (Kupffer cells, pit cells, T cells, newly recruited macrophages, and the activation state of macrophages) did not play a significant role in this diet-dependent outgrowth of tumors. In conclusion, omega-3 and omega-6 PUFAs promote colon cancer metastasis in the liver without down-regulating the immune system. This finding has serious implications for the treatment of cancer patients with fish oil diet to fight cachexia.

Lipids. 1987 Jun;22(6):445-54.
Effects of fatty acids on gap junctional communication: possible role in tumor promotion by dietary fat.
Aylsworth CF, Welsch CW, Kabara JJ, Trosko JE.
Dietary lipids, in particular unsaturated fat, promote the development of many experimental tumors. However, no mechanisms to fully explain these effects have been elucidated. Recent reports, which we summarize here, suggest a role for gap junction-mediated intercellular communication in the process of tumor promotion. We also review tumor-promoting effects of dietary fat on experimental, particularly mammary, carcinogenesis. Our main focus is to review recent data examining the inhibitory effects of unsaturated fatty acids on metabolic cooperation in Chinese hamster V79 cells. These data suggest that inhibition of junctional communication may be involved mechanistically in the promotion of tumors by high levels of dietary unsaturated fat. Finally, potential mechanisms by which unsaturated fatty acids inhibit metabolic cooperation are examined.

Nutr Cancer. 1984;6(2):77-85.
Enhancement of 1,2-dimethylhydrazine-induced large bowel tumorigenesis in Balb/c mice by corn, soybean, and wheat brans.
Clapp NK, Henke MA, London JF, Shock TL.
This study was designed to determine the effects of four well-characterized dietary brans on large bowel tumorigenesis induced in mice with 1,2-dimethylhydrazine (DMH). Eight-week-old barrier-derived male Balb/c mice were fed a semisynthetic diet with 20% bran added (either corn, soybean, soft winter wheat, or hard spring wheat) or a no-fiber-added control diet. Half of each group was given DMH (20 mg/kg body weight/week, subcutaneously for 10 weeks) beginning at 11 weeks of age. Surviving mice were killed 40 weeks after the first DMH injection. Tumors were not found in mice not subjected to DMH. In DMH-treated mice, tumors were found almost exclusively in the distal colon. Tumor incidences were as follows: controls, 11%; soybean group, 44%; soft winter wheat group, 48%; hard spring wheat group, 58%; and corn group, 72%. Tumors per tumor-bearing mouse ranged from 1.4 to 1.6, except in the corn group, which had 2.1. A positive correlation was found between percentage of neutral detergent fiber in the brans and tumor incidences but not between the individual components of cellulose, hemicellulose, or lignin. The enhancement of DMH-induced large bowel tumorigenesis by all four bran types may reflect a species and/or mouse strain effect that is bran-source related. These data emphasize the importance of using well-defined bran in all “fiber” studies.

Lipids. 1987 Jun;22(6):455-61.
The influence of dietary medium chain triglycerides on rat mammary tumor development.
Cohen LA, Thompson DO.
The N-nitrosomethylurea rat mammary tumor model was used to compare the tumor-promoting effects of a high-fat (HF) diet containing a 3:1 mixture of medium chain triglycerides (MCT) and corn oil with that of a HF and a low-fat (LF) corn oil diet. The serum and tumor lipid content and fatty acid (FA) composition were also determined in the three dietary groups. It was found that the MCT-containing diet failed to promote tumor development compared with the HF corn oil group. Tumor incidence in the HF-MCT group was similar to that of the LF corn oil group (5% fat, w/w), but significantly decreased compared to the HF corn oil group. Total serum cholesterol levels were significantly depressed in the HF corn oil group compared to the HF-MCT and LF corn oil groups. Analysis of serum and tumor FA profiles indicated that the HF corn oil group exhibited approximately twice the amount of linoleic acid (LA) as the other two treatment groups. Differences among the three groups in the major FA metabolite of LA, arachidonic acid, were minimal. These results are consistent with the hypothesis that tumor promotion by dietary fat is more a function of the type than the amount of fat ingested. In addition, they indicate that MCT, due at least in part to their unique structural and physiological properties, exert markedly different effects on mammary tumor development than conventional long chain unsaturated fatty acids.

Arch Intern Med. 1998 Jan 12;158(1):41-5.
A prospective study of association of monounsaturated fat and other types of fat with risk of breast cancer.
Wolk A, Bergström R, Hunter D, Willett W, Ljung H, Holmberg L, Bergkvist L, Bruce A, Adami HO.
Animal studies suggest that monounsaturated and polyunsaturated fat may have opposite effects on the risk of breast cancer.
We performed a population-based prospective cohort study, including 61,471 women aged 40 to 76 years from 2 counties in central Sweden who did not have any previous diagnosis of cancer; 674 cases of invasive breast cancer occurred during an average follow-up of 4.2 years. All subjects answered a validated 67-item food frequency questionnaire at baseline. Cox proportional hazards models were used to obtain adjusted rate ratio (RR) estimates with 95% confidence intervals (CIs).
After mutual adjustment of different types of fat, an inverse association with monounsaturated fat and a positive association with polyunsaturated fat were found. The RR for each 10-g increment in daily intake of monounsaturated fat was 0.45 (95% CI, 0.22-0.95), whereas the RR for a 5-g increment of polyunsaturated fat was 1.69 (95% CI, 1.02-2.78); the increments correspond to approximately 2 SDs of intake in the population. Comparing the highest quartile of intake with the lowest, we found an RR of 0.8 (95% CI, 0.5-1.2) for monounsaturated fat and 1.2 (95% CI, 0.9-1.6) for polyunsaturated fat. Saturated fat was not associated with the risk of breast cancer.
Our results indicate that various types of fat may have specific opposite effects on the risk of breast cancer that closely resemble the corresponding effects in experimental animals. Research investigations and health policy considerations should take into account the emerging evidence that monounsaturated fat might be protective for risk of breast cancer.

The Lancet, Volume 297, Issue 7697, Pages 464 – 467, 6 March 1971
Morton Lee Pearce, Seymour Dayton
In an eight-year controlled clinical trial of a diet high in polyunsaturated vegetable oils and low in saturated fat and cholesterol in preventing complications of atherosclerosis, 846 men were assigned randomly to a conventional diet or to one similar in all respects except for a substitution of vegetable oils for saturated fat. Fatal atherosclerotic events were more common in the control group (70 v.48; P<0·05). However, total mortality was similar in the two groups: 178 controls v. 174 experimentals, demonstrating an excess of non-atherosclerotic deaths in the experimental group. This was accounted for by a greater incidence of fatal carcinomas in the experimental group. 31 of 174 deaths in the experimental group were due to cancer, as opposed to 17 of 178 deaths in the control group (P=0·06).

Isr J Med Sci. 1996 Nov;32(11):1134-43.
Diet and disease–the Israeli paradox: possible dangers of a high omega-6 polyunsaturated fatty acid diet.
Yam D, Eliraz A, Berry EM.
Israel has one of the highest dietary polyunsaturated/saturated fat ratios in the world; the consumption of omega-6 polyunsaturated fatty acids (PUFA) is about 8% higher than in the USA, and 10-12% higher than in most European countries. In fact, Israeli Jews may be regarded as a population-based dietary experiment of the effect of a high omega-6 PUFA diet, a diet that until recently was widely recommended. Despite such national habits, there is paradoxically a high prevalence of cardiovascular diseases, hypertension, non-insulin-dependent diabetes mellitus and obesity-all diseases that are associated with hyperinsulinemia (HI) and insulin resistance (IR), and grouped together as the insulin resistance syndrome or syndrome X. There is also an increased cancer incidence and mortality rate, especially in women, compared with western countries. Studies suggest that high omega-6 linoleic acid consumption might aggravate HI and IR, in addition to being a substrate for lipid peroxidation and free radical formation. Thus, rather than being beneficial, high omega-6 PUFA diets may have some long-term side effects, within the cluster of hyperinsulinemia, atherosclerosis and tumorigenesis.

When cancers are mestatasizing, their phospholipids contain less stearic acid than the less malignant tumors (Bougnoux, et al., 1992), patients with advanced cancer had less stearic acid in their red blood cells (Persad, et al., 1990), and adding stearic acid to their frood delayed the development of cancer in mice (Bennett, 1984). The degree of unsaturation of the body’s fatty acids corresponds to resistance to several types of cancer that have been studies (Hawley and Gordon, 1976; Singh, et al., 1995). -Ray Peat, PhD

Breast Cancer Res Treat. 1992 Mar;20(3):185-94.
Prognostic significance of tumor phosphatidylcholine stearic acid level in breast carcinoma.
Bougnoux P, Chajes V, Lanson M, Hacene K, Body G, Couet C, Le Floch O.
The involvement of lipid enzymes in the action of oncogenes at the cell membrane level has suggested that membrane lipids could play a role in modulating the growth of tumors. We previously found that breast cancer patients with a low level of polyunsaturated fatty acids in their primary tumor’s phosphatidylethanolamine had a high risk of early occurrence of visceral metastasis. In the present study, we prospectively examined whether fatty acid composition of tumor membrane phosphatidylcholine had a prognostic significance in a series of 63 patients with a localized presentation of breast cancer. Membrane phospholipids were extracted from the carcinoma tissue obtained at the time of surgery, phosphatidylcholine was purified, and its fatty acids were analyzed by capillary gas chromatography. During the follow-up period, 20 patients developed metastasis. In these patients, the proportion of stearic acid containing phosphatidylcholine was significantly lower than it was in the tumors of the 43 patients who remained metastasis-free. Multivariate analysis according to Cox showed that low stearic acid level in tumor phosphatidylcholine and high mitotic index were independently predictive of subsequent metastasis. The predictive value of stearic acid level on metastasis risk was higher in node-positive patients than in node-negative patients, allowing individualization of a subgroup of low stearic acid level, node-positive patients with very poor prognosis. We concluded that stearic acid level in tumor membrane phosphatidylcholine is an independent intra-tumor marker of breast cancer prognosis. This finding is new evidence that tumor’s structural lipids are linked to the growth of breast cancer.

Br J Urol. 1990 Mar;65(3):268-70.
Erythrocyte stearic to oleic acid ratio in prostatic carcinoma.
Persad RA, Gillatt DA, Heinemann D, Habib NA, Smith PJ.
The red cell membrane stearic acid to oleic acid ratio was analysed in 34 men with histologically proven carcinoma of the prostate and distant metastases. This ratio was expressed as the saturation index (SI). A mean SI of 0.97 was found in control patients without evidence of any malignancy whereas all patients with advanced prostatic cancer showed a reduced stearic to oleic acid ratio (mean SI 0.466). Untreated patients had a significantly lower SI (mean 0.36) than those who had responded to hormonal therapy (mean 0.547; P less than 0.0001). A drop in SI correlated well with more advanced disease as judged by radiological findings and serum PSA. It is suggested that red cell membrane SI correlates well with radiological and biochemical markers of advanced prostatic carcinoma and may be used as a marker to assess progress and response to treatment.

Int J Cancer. 1984 Oct 15;34(4):529-33.
Effect of dietary stearic acid on the genesis of spontaneous mammary adenocarcinomas in strain A/ST mice.
Bennett AS.
Strain A/ST female mice maintained on a high fat (15%) diet in which stearic acid was the major lipid component developed initial spontaneous mammary adenocarcinomas at an older age than mice fed a low fat (4.5%) stock diet. Mice placed on the SA diet at weaning developed tumors at 15.7 +/- 0.87 months compared to 12.7 +/- 0.43 months for those retained on the stock diet (p less than .05). Placing mice on the SA diet at 11.5 months resulted in a smaller but significant increase in the latency period (5.0 +/- 0.86 vs 3.0 +/- 0.57 months +/- 0.57 mo), (p less than .05). Fatty acid analyses of non-tumorous mammary tissue from mid-pregnant mice and of tumor tissues showed that feeding large amounts of 18:0 did not result in increases in the proportion of 18:0. Significant reductions in the percentages of polyunsaturated fatty acids (PUFA) was found in tissues on mice fed the SA diet. The percentage of 18:2 was reduced in both types of tissues; 20:3 and 20:4 was reduced in tumor tissues. Distribution of C18 fatty acids in plasma membranes of tumors of mice fed the two diets were similar; percentages 18:2 was higher in plasma membranes of non-tumorous tissues of mice fed the SA diet. These results suggest that dietary stearic acid interferes with the availability of certain PUFA required for tumor production.

Lab Invest. 1976 Feb;34(2):216-22.
The effects of long chain free fatty acids on human neutrophil function and structure.
Hawley HP, Gordon GB.
Neutrophils from healthy volunteers were isolated and incubated with varying concentrations of albumin-bound long chain free fatty acids. Standard in vitro function tests including phagocytosis, bactericidal activity, and chemotaxis were performed after the incubation. It was found that unsaturated fatty acid (oleic acid) caused no changes in bactericidal activity and only moderate decreases in phagocytosis and chemotaxis at very high concentrations. Saturated fatty acid (palmitic acid) produced, at high concentrations, virtually complete inhibition of chemotaxis and moderate depression of phagocytosis and bactericidal ability. Most significantly, lower concentrations of saturated free fatty acids, within the range reported clinically in various diseases, caused a marked inhibition of chemotaxis. These functional disturbances were associated with ultrastructural alterations. Neutrophils treated with oleic acid contained numerous cytoplasmic neutral lipid droplets. Neutrophils incubated with palmitic acid showed elongated cleftlike dilations of the endoplasmic reticulum and degenerative degranulated cytoplasmic areas. It is postulated that these represent crystallization of excess saturated free fatty acids or triglyceride which interfere with chemotaxis, either mechanically or by causing cell injury.

Invasion Metastasis. 1995;15(3-4):144-55.
Stearate inhibits human tumor cell invasion.
Singh RK, Hardy RW, Wang MH, Williford J, Gladson CL, McDonald JM, Siegal GP.
Tumor growth and metastasis are affected by changes in membrane lipid composition, however, little is known regarding the role of specific fatty acids in these pathological events. We investigated the effects of the long-chain saturated fatty acids (LCSFA), myristate (C14:0), palmitate (C16:0) and stearate (C18:0) on two key steps of metastasis: cell adhesion and invasion into extracellular matrix (ECM). Using a new 72-hour ECM (Amgel) invasion assay, we demonstrated that the exposure of highly invasive human fibrosarcoma HT-1080 cells to 0.3 mM stearate inhibited their ability to traverse Amgel by 59.4 +/- 8%. In contrast, treatment of tumor cells with 0.3 mM myristate or palmitate had no effect. Microscopic examination revealed a time-dependent inhibition of tumor cell adhesion to the Amgel in the stearate-treated group. Cell adhesion assays further showed a series of rapid morphological cellular changes, i.e. retraction of processes, cell rounding, and subsequent detachment in the presence of stearate. These morphological events were both dose- and time-dependent. Viability of LCSFA-treated cells exceeded 80%. This stearate inhibition of HT-1080 cell adhesion was also observed with two other invasive human tumor cell lines. Similar treatment of HT-1080 cell with the unsaturated long-chain fatty acid oleate (C18:1) did not alter tumor cell adhesiveness. In contrast, nontransformed human fibroblasts (Hs-68) were unaffected by stearate treatment. This inhibition of cell adhesion by stearate was determined to be dependent upon laminin-containing ECM. Pretreatment of HT-1080 cells with stearate dramatically abolished their capacity to attach to laminin but not to collagen type IV or fibronectin matrices. Immunofluorescent studies with anti-beta 1 integrin receptor and antivinculin antibodies demonstrated beta 1 subunit and vinculin colocalization to focal adhesions in untreated HT-1080 cells adherent to laminin, in contrast to stearate-treated tumor cells. Further, stearate-induced changes were shown to be functionally coupled to integrins as an anti-beta 1 antibody markedly diminishes the adhesive ability of tumor cells to laminin. These data demonstrate stearate inhibits tumor cell adhesion, and therefore invasion, via a mechanism involving a laminin integrin receptor.

Nat Commun. 2012 Sep 11;3:1053.
High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring.
de Assis S, Warri A, Cruz MI, Laja O, Tian Y, Zhang B, Wang Y, Huang TH, Hilakivi-Clarke L.
“To test our hypothesis that maternal exposures during pregnancy to factors such as HF diet or a synthetic E2 lead to breast cancer in several generations, we fed pregnant Sprague–Dawley rats (F0) with either an AIN93G control diet or an isocaloric AIN93G-based high fat diet, containing 43% energy from corn oil, throughout gestation.”
“Maternal exposures to environmental factors during pregnancy influence the risk of many chronic adult-onset diseases in the offspring. Here we investigate whether feeding pregnant rats a high-fat (HF)- or ethinyl-oestradiol (EE2)-supplemented diet affects carcinogen-induced mammary cancer risk in daughters, granddaughters and great-granddaughters. We show that mammary tumourigenesis is higher in daughters and granddaughters of HF rat dams and in daughters and great-granddaughters of EE2 rat dams. Outcross experiments suggest that the increase in mammary cancer risk is transmitted to HF granddaughters equally through the female or male germ lines, but it is only transmitted to EE2 granddaughters through the female germ line. The effects of maternal EE2 exposure on offspring’s mammary cancer risk are associated with changes in the DNA methylation machinery and methylation patterns in mammary tissue of all three EE2 generations. We conclude that dietary and oestrogenic exposures in pregnancy increase breast cancer risk in multiple generations of offspring, possibly through epigenetic means.”

Cancer Res. 1987 Mar 1;47(5):1333-8.
Effects of dietary fats and soybean protein on azaserine-induced pancreatic carcinogenesis and plasma cholecystokinin in the rat.
Roebuck BD, Kaplita PV, Edwards BR, Praissman M.
Both dietary unsaturated fat and raw soybean products are known to enhance pancreatic carcinogenesis when fed during the postinitiation phase. A comparison of these two dietary components was made to evaluate the relative potency of each ingredient for enhancing pancreatic carcinogenesis and to determine if this enhancement was correlated with an increase in plasma cholecystokinin (CCK) levels. Male Wistar rats were initiated with a single dose of azaserine (30 mg/kg body weight) at 14 days of age. The rats were weaned to test diets formulated from purified ingredients. Dietary protein at 20% by weight was either casein or soy protein isolate (heat treated or raw). Corn oil was the unsaturated fat of major interest and it was fed at either 5 or 20% by weight. Pancreases were quantitatively evaluated for carcinogen-induced lesions at 2- and 4-month postinitiation. In a second experiment designed to closely mimic the above experiment, rats were implanted with cannulae which allowed plasma to be repetitively sampled over a 2.5-week period during which the test diets were fed. Plasma was collected both prior to introduction of the test diets and afterwards. Plasma CCK was measured by a specific radioimmunoassay. Both the 20% corn oil diet and the raw soy protein isolate diet enhanced pancreatic carcinogenesis. The effects of the raw soy protein isolate on the growth of the carcinogen-induced lesions were significantly greater than the effects of the 20% corn oil diet. Plasma CCK values were not elevated in the rats fed the 20% corn oil diet, but they were significantly elevated in the rats fed the raw soy protein isolate. Heat-treated soy protein isolate neither enhanced carcinogenesis nor elevated the plasma CCK level. This study demonstrates that certain plant proteins enhance the growth of carcinogen-induced pancreatic foci and that this effect is considerably greater than the enhancement by high levels of dietary unsaturated fat. Furthermore, the enhancement by the raw soy protein isolate may be mediated by CCK; but this does not appear to be the mechanism by which the unsaturated fat, corn oil, enhances pancreatic carcinogenesis.

Nutr Cancer. 1987;9(4):219-26.
Melanoma and dietary lipids.
Mackie BS, Mackie LE, Curtin LD, Bourne DJ.
Samples of subcutaneous adipose tissue were taken from 100 melanoma patients and 100 matched controls in Sydney in 1984-1985 and were analyzed for constituent fatty acids. The mean percentage of linoleic acid in the triglycerides of the subcutaneous adipose tissue (PLASAT) of these subjects was substantially higher than that in a similar group examined in 1975-1976. In addition, the percentage of polyunsaturated fatty acids was found to be higher in the melanoma patients than in the controls (p less than 0.01), and there were significantly more controls than patients who had a low PLASAT (p less than 0.01). Relevant literature is quoted and the suggestion is made that increased consumption of dietary polyunsaturates may have a contributory effect in the etiology of melanoma.

International Science and Investigation journal, [S.l.], v. 5, n. 5, p. 157-168, Nov. 2016
Vegetable Oils Consumption as One of the Leading Cause of Cancer and Heart Disease.
This review takes a deep look at increases in the incidence of cancer and heart disease after the introduction of industrial vegetable oils in the world. Most vegetable oils are highly processed and refined products, which completely lack the essential nutrients. Omega-6 Linoleic acid from vegetable oils increases oxidative stress in the body of humans, contributing to endothelial dysfunction and heart disease. The consumption of these harmful oils which are high in mega-6 polyunsaturated fats results in changing the structure of cell membrane which contribute to increasing inflammation and the incidence of cancer.

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