The Skinny on Fat.
- 03-27-2006, 10:24 AM
The Skinny on Fat.
I have seen numerous posts regarding dropping fat content to what I consider extremely low levels and I was hoping to spur some good discussion on the benefits of a properly balanced intake of the right type of fats. I will start it up with a few thoughts and studies and hope others will chime in with comments and additions.
Dietary fats supply some of the best, and most stable sources of energy. So if you want to feel good all day long, you need to make sure you are getting enough fats, and the right types. Our body's
need fat just to function properly, not only for optimal health but certain amounts of fat are necessary for proper hormone production. If hormone production is off so will your metabolism be. Hormones regulate many things in the body including your ability to build and maintain muscle tissue, which is responsible for a large portion of your energy expenditure. In simple terms, muscle burns calories 24 hours a day and if you eat a low fat or no fat diet you will have a hard time building and maintaining muscle.
Fats add to satiety of a meal making you feel more satisfied and slow digestion to aid in a more steady release of amino acids.
Olive oil is a great source of fat that has great health benefits.
Olive oil's health benefits
The greatest exponent of monounsaturated fat is olive oil, and it is a prime component of the Mediterranean Diet. Olive oil is a natural juice which preserves the taste, aroma, vitamins and properties of the olive fruit. Olive oil is the only vegetable oil that can be consumed as it is - freshly pressed from the fruit.The beneficial health effects of olive oil are due to both its high content of monounsaturated fatty acids and its high content of antioxidative substances. Studies have shown that olive oil offers protection against heart disease by controlling LDL ("bad") cholesterol levels while raising HDL (the "good" cholesterol) levels. No other naturally produced oil has as large an amount of monounsaturated as olive oil -mainly oleic acid.
Olive oil is very well tolerated by the stomach. In fact, olive oil's protective function has a beneficial effect on ulcers and gastritis. Olive oil activates the secretion of bile and pancreatic hormones much more naturally than prescribed drugs. Consequently, it lowers the incidence of gallstone formation.
Olive oil and heart disease
Studies have shown that people who consumed 25 milliliters (mL) - about 2 tablespoons - of virgin olive oil daily for 1 week showed less oxidation of LDL cholesterol and higher levels of antioxidant compounds, particularly phenols, in the blood.
But while all types of olive oil are sources of monounsaturated fat, EXTRA VIRGIN olive oil, from the first pressing of the olives, contains higher levels of antioxidants, particularly vitamin E and phenols, because it is less processed.
Olive oil is clearly one of the good oils, one of the healing fats. Most people do quite well with it since it does not upset the critical omega 6 to omega 3 ratio and most of the fatty acids in olive oil are actually an omega-9 oil which is monounsaturated.
Another great fat in my book that supplies the much overlooked EPA and DHA that most diets lack. I am not going to delve into the specific benefits right now but I will say that they will help make a leaner and smarter you.
So why not just use flax instead of nasty tasting fish? This is a little pet peeve of mine as I think flax is way over-rated.
Fish oil versus flax oil
There is considerable evidence that fish and fish oils are beneficial to heart health, reduce the risk of cancer, and benefit mental health. The “active” components of fish oils are eicosapentaenoic acid (EPA), a polyunsaturated fatty acid with 20 carbon atoms in its backbone, and docosahexaenoic acid (DHA), a polyunsaturated fatty acid with 22 carbon atoms. Both are members of the omega-3 group of essential fatty acids. EPA and DHA are found exclusively in marine animals; fatty fish such as herring, sardines, salmon and fresh tuna are the best sources.
Alpha-linolenic acid (ALA) is another omega-3 fatty acid found in flaxseed and flaxseed oil. ALA has 18 carbon atoms in its backbone and can be converted to EPA in the body (in the liver) by the addition of two carbon atoms. EPA, in turn, can be converted to DHA. Because the typical American diet is relatively low in fish intake ALA becomes a crucial source of the EPA and DHA required for optimum health.
Researchers at the National Institutes of Health have just completed a study designed to determine just how much ALA is actually converted to EPA in the body. Their study included eight healthy subjects who were fed a standard diet for three weeks and then given one gram of ALA labeled with an isotope tracer. The diet was beef-based in order to avoid extraneous sources of EPA and DHA. The researchers measured blood plasma concentrations of ALA, EPA and DHA 8, 24, 48, 72, 96 and 168 hours after ingestion of the labeled ALA.
The results show that only about 0.2 per cent of the ALA (2 mg) was actually converted to EPA. In contrast, about 23 per cent of the EPA was available for conversion to DHA. The researchers also noted that the half-life (the time it takes to reduce initial concentration by 50 per cent) of ALA in blood plasma was quite low at about one hour. In comparison, the half-life of EPA was 67 hours and that of DHA 20 hours.
The researchers conclude that ALA is not a viable source of EPA and DHA and cannot replace fish and fish oils in the diet. According to this new data a tablespoon of flax oil would only result in the synthesis of about 30 mg of EPA – far less than the recommended daily intake of 220 mg.
Thats all for now. Let the discussion roll. Would like to hear everyones thoughts on proper macro ratios in regards to fat intake whether your cutting, bulking or maintaining. Also, what sources you use to obtain dietary fats and why. Would also like to hear why it is easier to lose fat while eating fats, I have some theories but would love to hear from the GURU's!Recent log:http://anabolicminds.com/forum/supplement-reviews-logs/213350-lean-efx-refined.html
- 03-27-2006, 10:55 AM
For what it's worth I'm maintaining a roughly 40/40/20 macro breakdown with about 70% of my fat calories coming from poly/monounsaturated fats, 25% from saturated fat and around 5% transfat that I haven't managed to eliminate. I think it's coming from my protein powder, I have to look at the ingredients again and get that, see if I can't nix it. But, this basic diet has been working very well for weight loss over the last couple of months. all the beneits mentioned above, satiety, energy, etc., are found. Few if any midnight munchies are evident. It's pretty easy to stick to the diet even though it's pretty hypocaloric.
03-27-2006, 11:15 AM
A few studies out of many on fat intake and hormonal levels
Effects of dietary fat and fiber on plasma and urine androgens and estrogens in men: a controlled feeding study.
Division of Cancer Prevention and Control, National Cancer Institute, Bethesda, MD 20892-7326, USA. [email protected]
We conducted a controlled feeding study to evaluate the effects of fat and fiber consumption on plasma and urine sex hormones in men. The study had a crossover design and included 43 healthy men aged 19-56 y. Men were initially randomly assigned to either a low-fat, high-fiber or high-fat, low-fiber diet for 10 wk and after a 2-wk washout period crossed over to the other diet. The energy content of diets was varied to maintain constant body weight but averaged approximately 13.3 MJ (3170 kcal)/d on both diets. The low-fat diet provided 18.8% of energy from fat with a ratio of polyunsaturated to saturated fat (P:S) of 1.3, whereas the high-fat diet provided 41.0% of energy from fat with a P:S of 0.6. Total dietary fiber consumption from the low- and high-fat diets averaged 4.6 and 2.0 g.MJ-1.d-1, respectively. Mean plasma concentrations of total and sex-hormone-binding-globulin (SHBG)-bound testosterone were 13% and 15% higher, respectively, on the high-fat, low-fiber diet and the difference from the low-fat, high-fiber diet was significant for the SHBG-bound fraction (P = 0.04). Men's daily urinary excretion of testosterone also was 13% higher with the high-fat, low-fiber diet than with the low-fat, high-fiber diet (P = 0.01). Conversely, their urinary excretion of estradiol and estrone and their 2-hydroxy metabolites were 12-28% lower with the high-fat, low-fiber diet (P < or = 0.01). Results of this study suggest that diet may alter endogenous sex hormone metabolism in men.
Relationships between types of fat consumed and serum estrogen and androgen concentrations in Japanese men.
Nagata C, Takatsuka N, Kawakami N, Shimizu H.
Department of Public Health, Gifu University School of Medicine, Japan.
The relationships between types of fat consumed and serum concentrations of estrone, estradiol, total and free testosterone, dihydrotestosterone, and sex hormone-binding globulin were examined in 69 Japanese men aged 43-88 years. Diet was assessed by a semiquantitative food frequency questionnaire. Intake of saturated, monounsaturated, and polyunsaturated fats was inversely correlated with serum total testosterone after controlling for age, total energy, body mass index, alcohol intake, and smoking status, but the correlation was statistically significant only for polyunsaturated fat (r = -0.29, p = 0.02). Intakes of eicosapentanoic and docosahexaenoic acids, n-3 fatty acids from fish, were significantly inversely correlated with total testosterone (r = -0.25, p = 0.04 and r = -0.32, p = 0.01, respectively). Serum estrone, estradiol, and free testosterone were not significantly correlated with any type of fat studied. The correlations of total testosterone with n-3 fatty acids from fish remained significant after additional adjustment for the other categories of fat (r = -0.27, p = 0. 03 for eicosapentanoic acid and r = -0.32, p = 0.01 for docosahexaenoic acid), while the correlations with saturated and monounsaturated fats became nearly null after the adjustment.
Low-fat high-fiber diet decreased serum and urine androgens in men.
Wang C, Catlin DH, Starcevic B, Heber D, Ambler C, Berman N, Lucas G, Leung A, Schramm K, Lee PW, Hull L, Swerdloff RS.
Department of Medicine and Pediatrics and the General Clinical Research Center, Harbor-University of California at Los Angeles Medical Center and Los Angeles Biomedical Research Institute, Torrance, California 90509, USA. [email protected]
To validate our hypothesis that reduction in dietary fat may result in changes in androgen metabolism, 39 middle-aged, white, healthy men (50-60 yr of age) were studied while they were consuming their usual high-fat, low-fiber diet and after 8 wk modulation to an isocaloric low-fat, high-fiber diet. Mean body weight decreased by 1 kg, whereas total caloric intake, energy expenditure, and activity index were not changed. After diet modulation, mean serum testosterone (T) concentration fell (P < 0.0001), accompanied by small but significant decreases in serum free T (P = 0.0045), 5 alpha-dihydrotestosterone (P = 0.0053), and adrenal androgens (androstendione, P = 0.0135; dehydroepiandrosterone sulfate, P = 0.0011). Serum estradiol and SHBG showed smaller decreases. Parallel decreases in urinary excretion of some testicular and adrenal androgens were demonstrated. Metabolic clearance rates of T were not changed, and production rates for T showed a downward trend while on low-fat diet modulation. We conclude that reduction in dietary fat intake (and increase in fiber) results in 12% consistent lowering of circulating androgen levels without changing the clearance.
Diet and serum sex hormones in healthy men.
Hamalainen E, Adlercreutz H, Puska P, Pietinen P.
The possible effect of dietary fat content and the ratio of polyunsaturated to saturated fatty acids (P/S-ratio) on serum sex hormones was studied in 30 healthy male volunteers. The customary diet of the subjects, which supplied 40% of energy as fat (mainly from animal sources, P/S-ratio 0.15) was replaced for a 6 weeks period by a practically isocaloric experimental diet containing significantly less fat (25% of energy) with a higher P/S-ratio (1.22) and other environmental factors were stabilized. Serum testosterone and 4-androstenedione decreased from 22.7 +/- 1.1 nmol/l to 19.3 +/- 1.2 nmol/l, (SEM, P less than 0.001) and from 4.6 +/- 0.2 nmol/l to 4.3 +/- 0.2 nmol/l (SEM, P less than 0.01), respectively. These changes were paralleled by a reduction in serum free (non-protein bound) testosterone (P less than 0.01) suggesting a possible change in biological activity. During the low fat period a significant negative correlation between serum prolactin and androgens was observed. All the changes in androgen levels were reversible. With the exception of a small but non-significant decrease in serum estradiol-17 beta, the other hormone parameters were practically unaffected by the dietary manipulation. Our results indicate that in men a decrease in dietary fat content and an increase in the degree of unsaturation of fatty acids reduces the serum concentrations of androstenedione, testosterone and free testosterone. The mechanism and importance of this phenomenon is discussed in the light of epidemiological and experimental data.
Dietary lipids: an additional regulator of plasma levels of sex hormone binding globulin.
Reed MJ, Cheng RW, Simmonds M, Richmond W, James VH.
The effect of dietary lipid consumption on plasma levels of sex-hormone binding globulin (SHBG), free testosterone and cholesterol was studied in 6 normal men. After consuming a diet with a high fat content (greater than 100 g fat/day) for two weeks, the mean plasma cholesterol level increased (p less than 0.02) while the mean SHBG level decreased (p less than 0.02). Changing the diet from one with a high fat to low fat content (less than 20 g fat/day) for a further two week period resulted in a significant reduction in mean plasma cholesterol level (p less than 0.001) while the mean SHBG level increased (p less than 0.01). The increase in plasma SHBG was associated with a significant decrease in the free testosterone fraction and free testosterone concentration. No significant changes were detected in plasma samples obtained from the same men during a control period. The results from this study demonstrate that dietary lipid intake is an additional factor involved in the regulation of plasma levels of SHBG.
03-27-2006, 03:10 PM
Artemis P. Simopoulos, M.D.The Center for Genetics, Nutrition and Health, Washington, D.C.
Human beings evolved on a diet that was lower in total fat and saturated fat, but contained equal amounts of omega-6 and omega-3 essential fatty acids. Linoleic acid (LA) is the major omega-6 fatty acid, and alpha-linolenic acid (LNA) is the major omega-3 fatty acid. In the body, LA is metabolized to arachidonic acid (AA), and LNA is metabolized to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The ratio of omega-6 to 3 essential fatty acids was 1 to 2:1 with higher levels of the longer chain polyunsaturated fatty acids (PUFA), such as EPA, DHA and AA, than today’s diet. Today this ratio is about 10-20:1, indicating that Western diets are deficient in 3 fatty acids compared with the diet on which humans evolved and their genetic patterns were established. The 3 and 6 essential fatty acids are not interconvertible in the human body and are important components of practically all cell membranes. 6 and 3 fatty acids influence eicosanoid metabolism, gene expression, and intercellular cell to cell communication. The PUFA composition of cell membranes is, to a great extent, dependent on dietary intake. Therefore, appropriate amounts of dietary 6 and 3 fatty acids need to be considered in making dietary recommendations. These two classes of PUFA should be distinguished because they are metabolically and functionally distinct and have opposing physiological functions; their balance is important for homeostasis and normal development. A balanced omega-6/omega-3 ratio in the diet is essential for normal growth and development and should lead to decreases in cardiovascular disease and other chronic diseases, such as diabetes, hypertension, arthritis and other autoimmune diseases, and improve mental health. Although a recommended dietary allowance for essential fatty acids does not exist, an adequate intake (AI) has been estimated for omega-6 and omega-3 essential fatty acids by an international scientific working group. For Western societies, it will be necessary to decrease the intake of omega-6 fatty acids and increase the intake of omega-3 fatty acids. The food industry is already taking steps to return omega-3 essential fatty acids to the food supply by enriching various foods with omega-3 fatty acids. To obtain the recommended AI, it will be necessary to consider the issues involved in enriching the food supply with omega-3 PUFA in terms of dosage, safety, and sources of omega-3 fatty acids.
ω-3 LIPIDS AND VITAMIN E SUPPLEMENTS ON IMMUNE FUNCTIONS IN RA-PRONE MICE
J. T. Venkatraman, Ph.D.
Department of Physical Therapy, Exercise & Nutrition Sciences
State University of New York, Buffalo, NY 14214.
ω-3 fatty acid rich-fish oil (FO) and vitamin E (vit-E) may delay the progress of certain autoimmune (AI) diseases. The present study examined the mechanism of action of ω3 and ω6 lipids and vit-E in autoimmune-prone MRL/lpr (lpr) mice. The lpr (lymphoproliferative) gene is overexpressed in these mice and they suffer from extensive lymphoproliferation, lupus-like symptoms and accelerated aging. To determine whether the effects of ω-3 lipids in autoimmune disease (AI) is linked to vit-E levels, weanling female MRL/lpr (lpr) and congenic control MRL/+/+ (+/+) mice were fed semipurified diets containing 10% corn oil (CO), 10% fish oil (FO), at two levels of vit-E (75 IU or 500 IU/kg diet) for 4m and cellular immune functions were measured. Proliferative response to lectins was significantly higher in the groups fed the high-vit E diets. The type of oil had significant effects on IL-4, IL-10, IL-12 and pro-inflammatory cytokines (TNF-α, PGE2 and TXB2) while vit-E levels had significant effects on IL-2, IFN-γ and TNF-α levels. Strain had significant effects on IL-2, IL-10, IL-12, IFN-γ, TNF-α, PGE2 and TXB2 levels IL-1 while IL-6 levels were not affected.
The level of anti-DNA antibodies in sera were significantly higher in lpr mice. FO significantly decreased IL-12, TNF-α and TXB2 levels compared to the CO fed groups. However, PGE2, IL-1, IL-2, IFN-γ, IL-4, IL-6, and IL-10 did not show differences between the two oils. The expression of IL-12 and TNF-α was significantly higher in the low vit-E groups, but not IL-1, IL-2, IFN-γ, IL-4, IL-6, IL-10 and the hormones. The levels of IL-1, IL-2, and IFN-γ were lower while IL-4, IL-6, IL-10, IL-12, and TNF-α were higher in lpr mice. The production of chemokines RANTES and MCP-1 by spleen cells was higher in MRL/lpr mice. FO decreased the production of these two chemokines by spleen cells in the MRL/lpr mice.
Autoimmune mice generally express lower activities and mRNA levels of liver antioxidant enzymes and generate higher levels of TBARS. Both FO and vit-E can significantly decrease the generation of TBARS and increase the levels of antioxidant enzymes.
In summary, data from this study suggest that adding appropriate levels of vit-E to FO diets may further enhance the beneficial effects of ω-3 lipids in delaying AI. The present study suggests that ω-3 lipids containing appropriate levels of vit-E may delay AI through modulating the levels of selected cytokines chemokines, and enzymes involved in antioxidant defense. Vit-E seems to exert selective effects on proliferative response and specific subsets and selected cytokines. (Supported by NIAMS (NIH) grant # 1R15AR/A143517).
N-3 Fatty Acid Supplements in Rheumatoid Arthritis
Joel M. Kremer M.D.
Albany Medical College, Albany, NY
Ingestion of dietary supplements of n-3 fatty acids has been consistently shown to reduce both the number of tender joints on physical examination and the amount of morning stiffness in patients with rheumatoid arthritis. In these cases, supplements were consumed daily in addition to background medications and the clinical benefits of the n-3 fatty acids were not apparent until they were consumed for 12 wks or longer. It appears that a minimum daily dose of 3g eicosapentaenoic and docosahexaenoic acids is necessary to derive the expected benefits.
These doses of n-3 fatty acids are associated with significant reductions in release of leukotriene B4 from simulated neutrophils and interleukin 1 from monocytes. Both of these mediators of inflammation are thought to contribute to the inflammatory drugs or disease modifying anti rheumatic drugs. Because the methods used to determine whether patients taking n-3 supplements can discontinue taking these agents are variable, confirmatory and definitive studies are needed to settle this issue. n-3 fatty acids have virtually no reported serious toxicity in the dose range used in rheumatoid arthritis and are generally very well tolerated.
Dietary Omega-3 Polyunsaturated Fatty Acids Reduce Interleukin-12 and Interferon-gamma Production and Can Adversely Affect Host Infectious Disease Resistance
Kevin L. Fritsche, Ph.D.
University of Missouri, Columbia, MO
The overall goal of my research program is to define the molecular and cellular mechanisms that explain how and why dietary fats both positively and negatively impact our immune system. Recently, my laboratory has focused on the effect of omega-3 fatty acids on infectious disease resistance. Specifically, we study the influence of dietary fatty acids on murine listeriosis, a well-characterized infectious disease model. During the previous five years my laboratory has demonstrated that mice fed a diet rich in n-3 fatty acids have impaired resistance to Listeria. Further, these fatty acids reduce the in vivo production of interleukin-12 (IL-12) and interferon-gamma (IFNγ) during an infectious challenge in mice. These two cytokines play a central role in regulating both innate and adaptive (i.e., cell-mediated) immune responses against many infectious pathogens. We also demonstrated that n-3 PUFA consumption leads to a reduction in the expression of IFNγ receptors on immune cells. Mice with a gene deletion for the IFNγ receptor are highly susceptible to infection from intracellular pathogens, such as Listeria and mycobacterium. The objectives of our current research efforts are to: (1) further characterize the impact of n-3 PUFA on host resistance to Listeria, with an emphasis on the adaptive arm of the immune system; (2) determine if the n-3 PUFA-mediated reduction of IFNγ receptor expression makes a significant contribution to impair host resistance against Listeria; (3) define the molecular mechanism(s) through which n-3 PUFA affect interleukin-12 production. Data from some of our most recent studies will be presented.
Development of a Safe and Effective Dietary Fatty Acid Supplement that Reduces Leukotriene Generation in Humans.
Floyd H.Chilton, Ph.D.
Wake Forest University, Winston-Salem, NC
Studies carried out over the last two decades have revealed that controlling dietary fatty acid intake in a number of animal models has great potential in reducing arachidonic acid metabolism and ameliorating inflammation in models which mimic human arthritis, asthma or glomerulonephritis. However, dietary modifications in humans on Western diets have shown only modest efficacy. Over the past decade, our laboratory has performed dietary fatty acid reduction and supplementation studies in humans fed in a General Clinical Research Center in an attempt to influence arachidonic acid metabolism and clinical outcomes. Initial studies revealed that n-3 fatty acids provided with Western diets were rapidly incorporated into membrane phospholipids of inflammatory cells. However, dietary n-3 fatty acids at supplement concentrations as high as 5.6g eicosapentaenoic (EPA) acid/day did not reduce cellular arachidonic acid content nor significantly reduce the biosynthesis of lipid mediators of inflammation. In contrast, supplementation of human diets with γ-linolenic acid (GLA), an 18-carbon n-6 fatty acid, dramatically reduced leukotriene production in neutrophils and whole blood. However, this same fatty acid caused a marked increase in serum arachidonate (AA) levels, a potentially harmful side effect. This paradox was resolved by experiments that demonstrated that inflammatory cells such as human neutrophils contain an elongase but not a Δ-5 desaturase activity, and thus dietary GLA leads to the accumulation of dihomogammalinolenic acid (an inhibitor of AA metabolism) and not AA in neutrophil lipids. In contrast, the liver converts GLA to AA utilizing both elongase and Δ-5 desaturase activities, and this causes an increase in serum AA levels.
Thus, dietary supplement strategies were designed to maintain the capacity of GLA to reduce leukotrienes without causing elevations in serum AA levels. Initial in vitro experiments revealed that addition of the n-3 fatty acid, EPA, to liver cells blocked Δ-5 desaturase, the terminal enzyme step in AA synthesis. Addition of 3.0g/day of EPA and GLA to human diets decreased leukotrienes, increased serum levels of EPA and concomitantly prevented the increase in serum AA levels. Clinical trials were then performed to optimize GLA and EPA concentrations required to reduce whole blood leukotriene generation and prevent serum AA accumulation, respectively. In collaboration with Pilot Therapeutics, oils containing these fatty acids have been formulated into a good-tasting concentrated liquid emulsion that can be easily mixed with water or juice and taken as a single daily dose. Clinical trials are currently ongoing to test the capacity of this formulation to reduce leukotriene generation in asthmatics.
Diet Modulation of Apoptosis.
Robert S. Chapkin1,3, David N. McMurray 1,2,3 and Joanne R. Lupton 1,3,
1Faculty of Nutrition, 2Department of Medical Microbiology and Immunology, and the 3Center for Environmental and Rural Health,
Texas A&M University, College Station, TX.
We have demonstrated that the balance between cell proliferation and apoptosis can be favorably modulated by feeding fish oil, containing n-3 polyunsaturated fatty acids (PUFA). For example, dietary fish oil reduces O6-methylguanine DNA adduct levels in the rat colon in part by increasing targeted apoptosis during tumor initiation. This is significant because dietary upregulation of apoptosis can prevent malignant transformation of genetically damaged cells, lymphoproliferative disorders and autoimmunity. We have subsequently utilized the colonic epithelium and spleen-derived T-lymphocytes as model systems to determine the mechanisms by which n-3 PUFA promote apoptosis.
Dietary fish oil blunts signaling programs which attenuate apoptosis. Specifically, fish oil blocks carcinogen-induced suppressors of apoptosis in the colon, i.e., oncogenic ras activation, COX II and bcl-2 expression, diacylglycerol formation and protein kinase C (PKC) beta II and lambda/iota activation in the colon. This may partly explain why dietary fish oil protects against colon cancer development. In parallel studies, mice fed highly purified ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) had suppressed levels of several mitogenic second messengers, i.e., diacylglycerol, ceramide, IL-2 and IL-2 receptor alpha in stimulated T-lymphocytes, resulting in a proapoptotic, antiinflammatory phenotype. Collectively, these data demonstrate that the cellular homeostatic balance between cell proliferation and apoptosis can be favorably modified in diverse cell types solely by ingesting n-3 PUFA. This research was supported by grants from the American Institute for Cancer Research 00A055, NIH CA59034, CA61750, DK53055, and NIEHS ES09106.
N-3 Fatty Acids, Calories, and SLE
Gabriel J. Fernandes, PhD
University of Texas Health Science Center, San Antonio, Texas
Systemic Lupus Erythematosus (SLE) is an autoimmune disease that affects 1/2 to 2 million people in the USA, mostly women. SLE primarily affects the joints, skin, kidneys, lungs, heart, and GI tract, etc. Treatment includes immunosuppressive drugs but side effects are often noted. In limited clinical trials omega-3 fatty acids were used. The results were somewhat inconclusive. One of the earlier negative results may have been due to large doses of fish oil without adequate antioxidant supplements, which may have caused side effects. Well designed studies with concentrated odorless fish oil capsules may provide beneficial effects including likely reduction in the dosage of drugs used to treat the disease. Fish oil studies carried out in autoimmune prone mice by several investigators consistently revealed beneficial effects such as delayed onset of renal disease, decreased anti-DNA antibodies, and decreased proinflammatory cytokines. Our earlier studies were designed to investigate the role of corn oil (n-6) vs n-3 fatty acid supplementation. The results showed that n-3 fatty acid supplementation causes elevated antioxidant enzymes, decreased pro-inflammatory cytokine mRNA, reduced renal disease and prolonged life span in (NZBxNZW)F1 (B/W) female mice.
It is also well known that calorie restriction prevents obesity and delays age-related immune dysfunction and prolongs life span in multiple animal models. The amount and type of dietary fatty acids can also profoundly affect life span. We examined the influence of calorie restriction (40% reduction in energy intake) combined with substitution of fish oil for corn oil (5%). Autoimmune-prone B/W female mice, which develop fatal autoimmune renal disease, were used. The calorie-restricted/fish oil diet maximally extended median life span to 645 days (vs. 494 days for the calorie-restricted corn oil diet). Similarly, fish oil prolonged life span in the ad libitum fed mice to 345 days (vs. 242 for the ad libitum/corn oil diet, p<0.001). Increased life span was partially associated with decreased body weight, blunting renal proinflammatory cytokine (interferon-γ, interleukins-10 and -12 and tumor necrosis factor-α) levels and lower nuclear factor kappa B (NF-κB). Reductions in NF-κB were preceded by enhanced superoxide dismutase, catalase, and glutathione peroxidase activities in young mice before the onset of autoimmune disease. Our current findings demonstrate the profound additive effects of caloric restriction and n-3 fatty acids in prolonging life span in B/W mice (submitted). In summary, it appears that either a modest reduction in food or calorie intake and/or following a moderate regimen of exercise along with drug therapy and/or n-3 fatty acid supplements may have several beneficial effects, including decreased free radicals and increased T cell immunity, in the management of obesity, diabetes, cancer and/or the aging process including various autoimmune disorders. New experimental and clinical studies are needed to confirm or refute these hypotheses.
1. Avula, C. P., and Fernandes, G., Modulation of antioxidant enzymes and apoptosis in mice by dietary lipids and treadmill exercise, J Clin Immunol, 19, 35-44 1999.
2. Jolly, C. A., and Fernandes, G., Dietary N-3 fatty acids and calorie restriction in autoimmune disease: Influence in different immune compartments, Current Organic Chemistry, 4, 945-957 2000.
3. Lim, B. O., Jolly, C. A., Zaman, K., and Fernandes, G., Dietary (n-6) and (n-3) fatty acids and energy restriction modulate mesenteric lymph node lymphocyte function in autoimmune-prone (NZB x NZW)F1 mice, J Nutr, 130, 1657-64 2000.
4. Muthukumar, A. R., Jolly, C. A., Zaman, K., and Fernandes, G., Calorie restriction and n-3 fatty acid supplementation modulate pro-inflammatory cytokines and polymeric Ig receptor expression in the submandibular glands of autoimmune prone (NZB x NZW) F1 mice, J Clin Immunol, 20, 354-361 2000.
Omega-3 Fatty Acids in the Treatment of Patients with IgA Nephropathy: The Rationale and the Studies
James V. Donadio, M.D.
Mayo Clinic and Foundation, Rochester, MN
Idiopathic immunoglobulin A nephropathy (IgAN) is an immune-complex mediated glomerulonephritis characterized by the predominant or codominant deposition of IgA within the mesangial regions of the glomeruli associated with a variety of histopathologic lesions. IgAN is the most common glomerular disease worldwide. IgAN occurs at all ages with the usual age of clinical onset in the second and third decades of life. Clinical presentation includes episodic, macroscopic hematuria often coinicident with upper respiratory infection or asymptomatic proteinuria and microscopic hematuria. Renal biopsy is essential for making an accurate diagnosis. The disease has a poorly understood pathogenesis. Progressive renal failure develops up to 25 yr after diagnosis in 20%-40% of patients, although there is considerable variability in the clinical course of different groups of patients. There is no currently approved treatment for patients with IgAN. Three therapeutic agents have emerged as the most promising -- corticosteroids, angiotensin-converting-enzyme inhibitors, and omega-3 fatty acids -- and all have been tested, or are currently undergoing testing, in randomized clinical trials. Of the 4 trials testing efficacy of omega-3 fatty acids, 2 showed that such treatment stabilized renal function while 2 reported a decline in renal function. The findings of the largest study, which comprised 106 patients and was conducted by my collaborative group, provided strong evidence that in high-risk patients, treatment for 2-yr with a daily dose of 1.8g EPA and 1.2g DHA retarded the loss of renal function. From our 2-yr double-blind study and our extended observational study we conclude that early and prolonged treatment with omega-3 fatty acids slows renal disease progression for high-risk patients with IgAN.
Omega-3 fatty acids inhibit mesangial cell proliferation in vitro and in vivo.
Joseph P Grande, M.D.
Mayo Clinic and Foundation, Rochester, MN
Mesangial cell proliferation is a characteristic feature of IgA nephropathy. Recent clinical studies have shown that dietary ω -3 fatty acid supplementation retards renal disease progression in patients with IgA nephropathy. Potential mechanisms underlying this protective effect of ω -3 fatty acids have not been defined. We sought to test the hypothesis that ω -3 fatty acids reduce mesangial cell proliferation following acute renal injury, using the anti-thy-1.1 (ATS) model of mesangial proliferative glomerulonephritis. Subcultured rat mesangial cells were used to determine the in vitro effects of eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA), the primary components of fish oil, on proliferation. ω -3 fatty acids were extracted from OmacorTM capsules, and administered twice daily by gavage; the daily dose was approximately 4.7 g/kg EPA and 3.7 g/kg DHA. Following ATS administration, proteinuria was significantly decreased in animals treated with ω -3 fatty acids, compared with sesame oil-treated controls. In ATS rats given ω -3 fatty acids, there was less mesangial cell and matrix expansion, mesangiolysis, or basement membrane disruption (Δ % = -40%). ATS rats receiving fish oil had less glomerular cell proliferation (PCNA (Δ % = -50%) and a reduction of α smooth muscle actin expression (Δ % = -27%) by glomerular mesangial cells. In subcultured rat mesangial cells, DHA, but not EPA, significantly inhibited proliferation. In the ATS glomerulonephritis model, ω -3 fatty acids inhibit mesangial cell activation and proliferation, reduces proteinuria, and decreases histologic evidence of glomerular damage. In vitro, the antiproliferative effects are more likely related to the action of DHA. We suggest that orally administered fish oil, or purified DHA, may have a suppressive effect in the acute phase or relapses of glomerulopathies by inhibiting activation and proliferation of mesangial cells.
Dietary Supplementation with L-arginine and Canola Oil Reduces Rejection Episodes, Renal Biopsies, Rehospitalization and Blood Pressure Following Renal Transplantation
J. Wesley Alexander 1, Trisha Ofstedal 1, Libby Stanley 1, Ann Erickson 2, Norman Greenberg 2, Laura James 1, M. Roy First 1, James F. Whiting 1 and E. Steve Woodle 1. 1, University of Cincinnati College of Medicine, Cincinnati, Ohio; 2, and Novartis Nutrition, St Louis Park , Minnesota.
Studies in laboratory animals receiving minimal immunosuppression have shown that supplementation of the diet with immunonutrients can prolong allograft survival. The present study was performed to determine whether similar results could be achieved in adult renal allograft transplant patients receiving standard Neoral®, CellCept® and steroids as their initial immunosuppression. Patients were stratified for major risk factors and prospectively randomized to control (C, 54) of supplement (S, 49). All patients received a low fat diet, but S patients also received arginine (4.5g BID) and canola oil (15g BID) daily. Demographics for C and S patients were similar with 55% Cad donor in the C group and 52% Cad donor in the S group. Patients were censored at different times for noncompliance, withdrawal, or loss of kidney. Follow-up was available for 40, 35 and 23 S patients and 49, 46 and 26 C patients at 3, 6 and 12 months respectively. Excluding 2 C and 2 S patients with a rejection episode in the first week, there were 13 rejection episodes in 12 C patients compared to 3 in 2 S patients (p=0.029). Furthermore, there were 24 renal biopsies for dysfunction in 19 C patients compared to 11 in 8 S patients (p=0.025). Serum creatinines at 3, 6 and 12 months for C patients were 1.52, 1.52 and 1.58 compared to 1.45, 1.42 and 1.61 for S patients (p=NS). Systolic blood pressure fell by 10.5%, 9.6% and 19.26% in C patients vs. 12.8%, 16.5% and 26.6% in S patients at 3,6 and 12 months (p=.0001) despite 71% and 52% C patients taking antihypertensive drugs at 6 and 12 months compared to 52% and 47% S patients, respectively (p=NS). C patients gained 8.8 kg or 12.4% body weight at 12 months compared to 5.1 kg or 6.9% for S patients (p=NS). In patients with one year follow-up, 54% C and 39% S patients developed one or more infections; 4% in C group vs. 2% in S group developed CMV infections. Two patients lost a kidney from rejection in the C group whereas no kidneys were lost from rejection in the S group. The length of rehospitalization per patient over 1 year for C patients was 6.5 + 1.4 days compared to 3.0 + 0.9 days for S (p=0.039). We conclude that dietary supplementation with arginine and canola oil results in significant reduction in rejection episodes, improved blood pressure and shorter rehospitalization stay in renal transplant patients receiving initial CsA base therapy without having any adverse effects. Transplant 2000 Joint Meeting.
03-27-2006, 03:25 PM
great thread.. Nice work Bpmartyr..
I've long been a huge proponent of higher healthy fat intake.
Low fat diets are notorious for failing. Most low fat foods are MUCH higher in GI than their regular counterparts.
03-27-2006, 08:57 PM
03-28-2006, 09:09 AM
Anyone read "Natural Hormonal Enhancement" by Rob Faigin? Its basically a higher fat diet with carb-loading meals every 3/4 days (Sun/Wed).
03-28-2006, 11:18 AM
03-28-2006, 04:21 PM
The problem is Rob Faigin's science is pretty crap mainly based on the fact that he thinks GH is massively anabolic (even if it is it requires insulin to perform and that is not being provided as it is low-carb) and also he overestimates/misunderstands gloucagon's role in human metabolism (it is vastly more important when it comes to fat cells in animals)Originally Posted by AceDeuce
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