Dietary fat,fatty acids and prostate cancer

International comparisons suggest a relationship between prostate cancer incidence and dietary fat, an inference supported by migration studies, the changing incidence rates and levels of animal fat consumption in Japan and the results from some case-control studies. Overall, however, epidemiological studies have been inconclusive, and although prostate cancer is one of the hormone-dependent tumors, evidence of interactions between dietary fats and male endocrine function is incomplete. Laboratory experimentation has shown that n−6 fatty acids stimulate and n−3 fatty acids inhibit human prostate cancer cells in culture; also, feeding diets rich in marine oils suppresses growth of these cells as solid tumors in athymic nude mice. These growth effects of polyunsaturated fatty acids appear to involve both prostaglandins and leukotrienes and to interconnect with autocrine regulation by epidermal growth factor-related polypeptides. Based on a paper presented at the Sympsoium on Lipids in Cancer held at the AOCS Annual Meeting, Baltimore, MD, April 1990.     

Nonessential fatty acids in formula fat blends influence essential fatty acid metabolism and composition in plasma and organ lipid classes in piglets

The online version of the original article can be found at     

Nonessential fatty acids in formula fat blends influence essential fatty acid metabolism and composition in plasma and organ lipid classes in piglets

The n-6 and n-3 fatty acid status of developing organs is the cumulative result of the diet lipid composition and many complex events of lipid metabolism. Little information is available, however, on the potential effects of the saturated fatty acid chain length (8:0–16:0) or oleic acid (18:1) content of the diet on the subsequent metabolism of the essential fatty acids 18:2n-6 and 18:3n-3 and their elongated/desaturated products. The effects of feeding piglets formulas with fat blends containing either coconut oil (12:0±14:0) or medium chain triglycerides (MCT, 8:0±10:0) but similar levels of 18:1, 18:2n-6 and 18:3n-3, or MCT with high or low 18:1 but constant 18:2n-6 and 18:3n-3 on the fatty acid composition of plasma, liver and kidney triglycerides, phospholipids and cholesteryl esters, and of brain total lipid, were studied. Diet-induced changes in the fatty acid composition of lipid classes were generally similar for plasma, liver and kidney. Dietary 18:1 content was reflected in tissue lipids and was inversely associated with levels of 18:2n-6. Lower percentage of 18:2n-6, however, was not associated with lower levels of its elongated/desaturated product 20:4n-6 but was associated with higher levels of 22:6n-3. Feeding coconut oilvs. MCT resulted in lower 18:1 levels in all lipids, and higher percentages of 20:4n-6 in tissue phospholipid. Increasing the dietary n-6/n-3 ratio from 5 to 8 significantly increased tissue percentage of 18:2n-6 and decreased phospholipid 22:6n-3. In contrast to plasma, liver and kidney, brain lipid fatty acid composition was not influenced by the formula saturated fatty acid chain length, content of 18:1, or n-6/n-3 ratio. In summary, the studies show that the dietary requirement for n-6 and n-3 fatty acids may be influenced by the nonessential saturated and monounsaturated fatty acids fed concurrently.     

Dietary fat and fatty acids modulate cholesterol cholelithiasis in the hamster

We tested two hypotheses, i) whether the type and the amount of fat in the diet will affect the formation of cholesterol gallstones in the hamsters, and ii) whether palmitic acid, a major fatty acid component of butterfat, can act as a potentiator of cholesterol cholelithiasis in the hamster. Young, male golden Syrian hamsters (Sasco) were fed a semipurified diet containing casein, corn starch, cellulose and cholesterol (0.3%) to which various types and amounts of fat (butterfat, olive oil, menhaden oil, corn oil) were added. All diets contained 2% corn oil to supply essential fatty acids to the growing hamsters. No deaths or illness occurred during the experiment. Animals fed the semipurified diet plus 4% butterfat (group 1) had a gallstone incidence of 63%. Replacement of butterfat with either olive oil, corn oil or menhaden oil prevented the formation of cholesterol gallstones entirely (groups 2–4). When total butterfat was increased from 4% to 8% (group 8), the incidence of cholesterol gallstones increased to 80%. Substitution of 4% olive oil (group 5), corn oil (group 6), or menhaden oil (group 7) for the additional 4% butterfat significantly reduced gallstones to 35%, 45% and 30%, respectively. The replacement of 4% butterfat with 1.2% palmitic acid gave the highest incidence of cholesterol gallstones (95%). These results suggest that butterfat (and one of its components, palmitic acid) intensifies gallstone formation in this model whereas mono- and polyunsaturated fats act as inhibitors of cholesterol cholelithiasis. A fatty acid, possibly palmitic acid, appears to act as lithogen in our model.     

Dietary fat and the fatty acid composition of tissue lipids

Some characteristics of the fatty acid composition of animal tissue lipids are described and the origins of tissue fatty acids are discussed briefly. The effect of dietary fat on composition of tissue lipids is discussed. Types of dietary fatty acids for which experimental work is described include polyunsaturated fatty acids, short-chain fatty acids, fatty acids with chain length greater than C₁₈,trans unsaturated fatty acids, fatty acids with conjugated double bonds, acetylenic fatty acids, branched-chain fatty acids and oxygenated fatty acids. The individuality of fatty acids is discussed in relation to their roles as components of tissue lipids.     

Dietary nucleotides do not alter erythrocyte long-chain polyunsaturated fatty acids in formula-fed term infants

There have been conflicting reports regarding the effectiveness of dietary nucleotides (NT) to regulate tissue desaturases and hence stimulate accumulation of both n−6 and n−3 long-chain polyunsaturated fatty acids (LCPUFA). The aim of this study was to examine the effect of NT-supplemented cow's milk-based formula on erythrocyte phospholipid FA status in a large randomized controlled trial involving a well-nourished infant population born at term. Formula-fed infants were allocated to control formula with an innate level of NT at 10 mg/L (n=102), or formula fortified with NT at 34 mg/L (n=98). A parallel group of breastfed infants was included as a reference. Peripheral blood samples were collected by venipuncture at 7 mon of age and erythrocyte phospholipid FA determined by capillary GC. Erythrocyte LCPUFA levels did not differe between the NT-supplemented and control formula groups and were reduced in both groups compared with breastfed infants. We conclude that there is no induction of LCPUFa accumulation in erythrocyte phospholipids of term, formula-fed infants following 7 mon of NT supplementation.     

Maternal dietary conjugated linoleic acid alters hepatic triacylglycerol and tissue fatty acids in hatched chicks

The effects of feeding CLA to hens on newly hatched chick hepatic and carcass lipid content, liver TAG accumulation, and FA incorporation in chick tissues such as liver, heart, brain, and adipose were studied. These tissues were selected owing to their respective roles in lipid assimilation (liver), as a major oxidation site (heart), as a site enriched with long-chain polyunsaturates for function (brain), and as a storage depot (adipose). Eggs with no, low, or high levels of CLA were produced by feeding hens a corn-soybean meal-basal diet containing 3% (w/w) corn oil (Control), 2.5% corn oil +0.5% CLA oil (CLA1), or 2% corn oil +1.0% CLA oil (CLA2). The egg yolk content of total CLA was 0.0, 1.0, and 2.6% for Control, CLA1, and CLA2, respectively (P<0.05). Maternal dietary CLA resulted in a decrease in chick carcass total fat (P<0.05). Liver tissue of CLA2 chicks had the lowest fat content (P<0.05). The liver TAG content was 8.2, 5.8, and 5.1 mg/g for Control, CLA1, and CLA2 chicks, respectively (P<0.05). The chicks hatched from CLA1 and CLA2 incorporated higher levels of cis-9,trans-11 CLA in the liver, plasma, adipose, and brain than Control (P<0.05). The content of 18∶0 was higher in the liver, plasma adipose, and brain of CLA1 and CLA2 than Control (P<0.05), but no difference was observed in the 18∶0 content of heart tissue. A significant reduction in 18∶1 was observed in the liver, plasma, adipose, heart, and brain of CLA1 and CLA2 chicks (P<0.05). DHA (22∶6n−3) was reduced in the heart and brain of CLA1 and CLA2 chicks (P<0.05). No difference was observed in carcass weight, dry matter, or ash content of chicks (P>0.05). The hatchabilities of fertile eggs were 78, 34, and 38% for Control, CLA1, and CLA2, respectively (P<0.05). The early dead chicks were higher in CLA1 and CLA2 than Control (18 and 32% compared with 9% for Control), and alive but not hatched chicks were 15 and 19% for CLA1 and CLA2, compared with 8% for Control (P<0.05). Maternal supplementation with CLA leads to a reduction in hatchability, liver TAG, and carcass total fat in newly hatched chicks.     

Dietary polyunsaturated fat versus saturated fat in relation to mammary carcinogenesis

High levels of dietary fat have been shown to promote the development of mammary tumors induced in rats by 7,12-dimethylbenz(α)anthracene, and polyunsaturated fats were found to be more effective than saturated fats. In further studies it was found that diets containing 3% sunflowerseed oil (polyunsaturated fat) and 17% beef tallow or coconut oil (saturated fats) enhance tumorigenesis as much as a diet containing 20% sunflowerseed oil. Rats on these diets developed at least twice as many tumors as those fed diets containing either 3% sunflowerseed oil or 20% of the saturated fats alone. These results are in accord with human epidemiological data which show that breast cancer mortality in different countries is positively correlated with total fat intake but not with intake of polyunsaturated fat. Total fat intake varies greatly in different countries, but most human diets probably contain levels of polyunsaturated fat at least equivalent to 3% sunflowerseed oil.     

Dietary saturated and omega‐3 fatty acids affect growth and fatty acid profiles of Malaysian mahseer

The current study was conducted to determine optimal levels of dietary saturated fatty acids (SFA), n‐3 PUFA and to study potential n‐3 sparing effect of dietary SFA for Malaysian mahseer Tor tambroides. Juvenile T. tambroides were fed four trial diets with similar basal composition but different oil mixtures in a 2 × 2 factorial experimental design for 10 weeks. The two factors were the levels of dietary SFA and the levels of dietary n‐3 PUFAs. Growth performance and fatty acid profile of tissues were analyzed at the end of the experiment. Significant differences in growth performance were observed among treatments, and fish fed the diet low in n‐3 and high in SFA showed the best growth performance. T. tambroides fed the high n‐3 diets showed a significantly higher (p<0.05) muscle total n‐3 PUFA content compared to fish fed the low n‐3 diets. The highest 22:6 n‐3 and total n‐3 PUFA content of the liver were also observed in fish fed the low n‐3 and high SFA diet. However, the significant interaction (p<0.05) between dietary SFA and n‐3 PUFA levels was observed for the total n‐3 PUFA content of both muscle and liver tissues, suggesting an n‐3 sparing action by dietary SFA. The results of this study suggest that 2.5% n‐3 PUFA in the diet of T. tambroides, with an SFA to n‐3 ratio of 15.3, is sufficient to provide the best growth performance and to retain the n‐3 content of tissues. Practical applications: The continuous increase of world population and growth of aquaculture industry put severe pressure on the marine resources such as fish oil and fishmeal. Here we show that fish oil can be substituted with palm oil, a cheaper and more available source of oil in tropical countries, in the diet of Malaysian mahseer without a reduction of growth. Moreover, palm oil as a source of SFA may spare omega‐3 in the fish tissues. Omega‐3 is an essential fatty acid for humans as final consumer of edible fish.     

Cholesteryl ester and triacylglycerol fatty acids in type V hyperlipidemia

The fatty acid compositions of plasma cholesteryl esters (CE) and triacylglycerols (TG) from seven healthy individuals and five patients with type V hyperlipoproteinemia were determined. Very low density (VLDL), low density (LDL) and high density lipoproteins (HDL) were isolated. The lipids were extracted from the lipoproteins and the triacylglycerols and cholesteryl esters separated for analysis. The fatty acid compositions of triacylglycerols from healthy and type V individuals were very similar. The cholesteryl esters from type V patients had increased contents of palmitic and decreased amounts of linoleic and arachidonic acids as compared to the normal individuals. The fatty acid composition of the cholesteryl esters from the high density lipoproteins had the greatest deviation. The fatty acid compositions of the triacylglycerols from the two groups were similar. However, the triacylglycerols in all lipoprotein fractions contained more palmitic and oleic and less linoleic and arachidonic acids than the cholesteryl esters.     

Brown adipose tissue triacylglycerol fatty acids of obese and lean mice: In situ and in transplants

The triacylglcyerols of white adipose tissue (WAT) from animals with high rates of lipogenesis, such as obese hyperglycemic mice or hypothalamically lesioned rats, contain high proportions of palmitoleic acid (16∶1) and low proportions of linoleic acid (18∶2). These differences appear to result from dilution of dietary 18∶2 by synthesized fatty acids, particularly 16∶1. To test this we have investigated the triacylglycerol fatty acid composition of brown and white adipose tissue of lean and obese mice, as brown adipose tissue (BAT) has a higher lipogenic rate than WAT and lipogenesis is faster in obese than in lean mice. Between three and eight weeks of age the proportions of fatty acids in the tissues changed, with a marked fall in milk-derived lauric and myristic acids. From 8 to 16 weeks they were more stable and the proportions of 16∶1 and 18∶2 in the different tissues were as expected, with the highest and lowest proportions, respectively, in BAT from obese mice. When BAT from obese mice was transplanted under the kidney capsule of lean mice, or vice versa, for one month, the fatty acid composition of the grafts changed toward that of the host BAT. The proportions of 18∶2 and, to a lesser extent, 16∶1 were slightly higher in the grafts than in the hosts but since this also occurred in lean-to-lean and obese-to-obese grafts it was probably a transplantation artifact. Overall, the results confirm than the physiological environment, rather than the source of the adipose tissue, is the major determinant of its fatty acid composition.     

Stearic acid unlike shorter-chain saturated fatty acids is poorly utilized for triacylglycerol synthesis and β-oxidation in cultured rat hepatocytes

Utilization of stearate as compared to various saturated fatty acids for cholesterol and lipid synthesis and β-oxidation was determined in primary culture of rat hepatocytes. At 0.5 mmol/L in the medium, stearate (18:0) adequately solubilized by albumin was less inhibitory to cholesterol synthesis from [2-¹⁴C] acetate than myristate (14:0) and palmitate (16:0) (68% vs. 91 and 88% inhibition, respectively). The rate of incorporation into cholesterol from [1-¹⁴C] stearate (3.0±0.6 nmol/mg protein/4 h) was 37-, 1.8-, and 7.8-fold of that from myristate, palmitate, and oleate, respectively. Conversely, the rate of [1-¹⁴C] stearate incorporation into total glycerolipids was 88–90% lower than that of labeled palmitate, myristate, and oleate. The rate of [1-¹⁴C] stearate incorporation into triacylglycerol (3.6±0.4 nmol/mg protein/4 h) was 6–8% of that from myristate, palmitate, oleate, and linoleate. The rate of stearate incorporation into phospholipids was the lowest among tested fatty acids, whereas the rate of mono- and diacylglycerol synthesis was the highest with stearate treatment. The rate of β-oxidation as measured by CO₂ and acid soluble metabolite production was also the lowest with [1-¹⁴C] stearate treatment at 22.7 nmol/mg protein/4 h, which was 35–40% of those from other [1-¹⁴C] labeled fatty acids. A greater proportion of stearate than other fatty acids taken up by the hepatocytes remained free and was not metabolized. Clearly, stearate as compared to shorter-chain saturated fatty acids was less efficiently oxidized and esterified to triacylglycerol in cultured rat hepatocytes.     

Separation of fatty acids/triacylglycerol by membranes

Separation of fatty acids from triacylglycerol by membrane separation technique has been studied. Mixtures of triacylglycerols and fatty acids were extracted with alcohol, and the alcohol extracts were treated for recovery of oil by membrane separation technique. The membranes used were of both cellulosic and noncellulosic types. Polyamide membranes showed better selectivity toward fatty acid separation as compared to cellulose acetate and polysulfone membranes. For groundnut oil/fatty acid/alcohol mixture and a polyamide membrane, the free fatty acid (FFA) concentration in the permeate was 86.82% at 0.7 MPa pressure when the feed had 61.71% FFA. A reasonable permeate flux of 67.36 Im⁻²h⁻¹ was obtained. Results obtained have been useful in selecting membrane material suitable for such applications.     

Viscosities of fatty acids and methylated fatty acids saturated with supercritical carbon dioxide

The viscosities of several types of lipids saturated with supercritical carbon dioxide (SC-CO₂) were measured with a high-pressure capillary viscometer. Oleic acid and linoleic acid were evaluated from 85 to 350 bar at 40 and 60°C. The more SC-CO₂-soluble methylated derivatives of these fatty acids were evaluated from 90 to 170 bar at 40 and 60°C. The complex mixture of anhydrous milk fat (AMF) was evaluated from 100–310 bar at 40°C. The viscosities of the methylated fatty acids saturated with SC-CO₂ decreased between 5 and 10 times when the pressure increased from 1 to 80 bar, followed by a further decrease by a factor of 2 to 3 when the pressure was increased from 80 to 180 bar. The viscosities of the fatty acids and AMF saturated with SC-CO₂ had viscosity reduction similar to the methylated fatty acids between 1 and 80 bar, but they decreased much less between 80 and 350 bar. At constant pressure, the viscosity of the fatty acids and AMF decreased with increasing temperature, whereas the viscosity of the methylated fatty acids increased with increasing temperature. The lipid/SC-CO₂ mixtures were Newtonian, and their viscosities were best interpreted by using the mass concentration of dissolved SC-CO₂ in the lipids and the pure component viscosities.     

Effect of ethanol on utilization of plasma free fatty acids for liver triacylglycerol synthesis and its relation to hepatic triacylglycerol accumulation in rats

The effect of 3 different single doses of ethanol on the liver triacylglycerol concentration and on the metabolism of intravenously injected¹⁴C-oleic acid in fasted rats was studied. All 3 doses (2,3.75, and 6 g ethanol/kg body wt_ caused a rapid increased in the liver triacylglycerol concentration during the first 5–6 hr after the ethanol was given. Until the plasma ethanol concentration had fallen to low values, the high liver triacylglycerol levels were raised and were independent of the ethanol dose given. The incorporation of radioactivity from intravenously injected¹⁴C-oleic acid into liver triacylglycerols was increased over control values to the same extent in all rats given ethanol as long as the plasma ethanol concentration was above a low level. High rates of ethanol oxidation and increased utilization of plasma free fatty acids for liver triacylglycerol synthesis were closely correlated with the development and maintenance of the ethanol induced liver triacylglycerol accumulation.     

Influence of dietary saturated fatty acids on the regulation of plasma cholesterol concentration

The specific effects of individual fatty acids (FA) on plasma cholesterol levels, in the range habitually consumed by humans, is not usually presented by the literature. Conclusions have been made regarding the cholesterolemic effect of individual FA, even though these FA cannot be tested individually. It appears that FA balance of the diet may be more important than individual FA intakes. Variation in plasma cholesterol response to diet is influenced by many factors, such as gene-nutrient interactions. The effect on human health of current processes used in the food industry that are certain to change dietary fat composition and TG structure is yet to be fully explored. Some of the relevant research regarding dietary fat and plasma cholesterol levels is reviewed.     

Dietary saturated,monounsaturated, n−6 and n−3 fatty acids,and cholesterol influence platelet fatty acids in the exclusively formula-fed piglet

Platelet lipid composition is important to normal platelet morphology and function, and is influenced by dietary fatty acids and cholesterol. The fatty acid composition and cholesterol content of infant formulas differs from those of human milk, but the possible effects on platelet lipids in young infants is not known. This was studied in piglets fed from birth to 18 d of age with one of eight formulas differing in saturated fatty acid chain length, or content of 18∶1, 20∶5n−3 plus 22∶6n−3, or cholesterol. A reference group of piglets fed sow milk was also studied. Sow milk has a fatty acid composition and cholesterol content similar to that of human milk. Piglets fed formulas high in 18∶1 (34.9–40.8% wt fatty acids) and low in 16.0 (≤6.5% wt fatty acids) had lower platelet counts and greater platelet size than piglets fed sow milk (40.4% 18∶1, 30.7% 16∶0). Piglets fed formulas high in 16∶0 (27–29.6%) and 18∶1 (40–40.6%), or low in both 16∶0 (5.9–6.1%) and 18∶1 (10.8–11.2%), had similar platelet counts and size to piglets fed sow milk. Platelet phospholipid % 20∶4n−6 was lower in all the groups of piglets fed formula than in the group fed sow milk. Addition of fish oil with 20∶5n−3 plus 22∶6n−3 to the formula further decreased platelet phospholipid 20∶4n−6. Addition of cholesterol to the formula increased the platelet phospholipid % 20∶4n−6 and platelet volume.     

The saturated fatty acids of Japan wax

Summary Myristic and behenic acids, hitherto not reported therein, have been shown to be components of the glycerides of Japan “wax” in contrast to the nonexistence of an alleged heneicosanoic acid. Esterfractionation analysis revealed the following composition: myristic acid 1.9 per cent, palmitic acid 67.5 per cent, stearic acid 11.6 per cent, arachidic acid 0.04 per cent, behenic acid 0.01 per cent, unsaturated acids 13.6 per cent, and dicarboxylic acids 5.3 per cent. A preliminary investigation of the latter resulted in the isolation of an acid which by virtue of its melting point and molecular weight has been tentatively characterized as heneicosane dicarboxylic acid (C₂₃). However, final proof of identity must rest upon subsequent synthesis of this acid. This investigation is being supported by a grant from the Wisconsin Alumni Research Foundation whose aid is gratefully acknowledged.     

Separation of saturated/unsaturated fatty acids

Fatty acid mixtures can be separated into one fraction rich in saturated fatty acids and the other rich in unsaturated acids. Since saturated fatty acids have a higher melting point than unsaturated, liquid mixture to be fractionated is cooled to a temperature at which the larger part of the saturated acids crystallize, while the greater part of unsaturated acids remain in liquid form. Different industrial methods to separate the two phases are described. The oldest and simplest method is slowly to cool and crystallize the mixture in shallow pans to form cakes which then are pressed in presses of different design. By applying high pressure, the liquid olein is thus squeezed out from the cake, leaving the stearin fraction behind. A new process to separate the phases is to mix an aqueous solution, containing a wetting agent, with the crystallized fatty acid mixture. The stearin crystals are thus wetted and transferred into the aqueous phase, which then can be separated from the olein phase in a centrifuge. The stearin/aqueous suspension is heated to melt the stearin, which can then be separated in a second centrifuge. Other methods to improve phase separation use organic solvents, among which are methanol, acetone, methyl formate and propane. In the solvent fraction process, the miscella has to be cooled to a lower temperature than in the aforementioned methods, due to the solubility effect of the solvents. The solvents are removed by distillation from the fraction. Typical operation results with different types of raw materials are given. The advantages and disadvantages of the different methods are discussed.