SAFETY: Baylor Clinical Evaluation
Proceedings of the International Society of Sports Nutrition (ISSN) Conference June 15-17, 2006.
Changes in whole blood and clinical safety markers over 50 days of concomitant arachidonic acid supplementation and resistance training.
Wilborn, C, M Roberts, C Kerksick, M Iosia, L Taylor, B Campbell, T Harvey, R Wilson, M. Greenwood, D Willoughby and R Kreider. Exercise & Sport Nutrition Laboratory, Center for Exercise, Nutrition & Preventive Health Research, Baylor University, Waco, TX 76798-7313. Colin_Wilborn@baylor.edu.
Prostaglandins are derived from dietary arachidonic acid (AA) and up-regulate recovery mechanisms including inflammation and protein synthesis within skeletal muscle in response to resistance training. The purpose of this study was to determine if 50 days of concomitant resistance training and AA supplementation elicited changes in immune and serum clinical safety markers in resistance-trained males. Thirty-one subjects (22.1 ± 5.0 yrs, 86.1 ±1 3.0 kg, 178.9 ± 3.4 cm, 18.1 ± 6.4 % body fat) were randomly assigned to a placebo (P: n = 16; 1 g capsulated corn oil/day) or AA group (AA: n = 15; 1 g capsulated AA/day) and were given supplemental protein powder to ingest in order attain an adequate protein intake of 2 g/kg/day while participating in a 4 day/wk resistance training regimen (2 upper/ 2 lower). Fasting blood was taken on days 0, 25 and 50. Immune markers were measured from whole blood using flow cytometric analysis (Abbott Cell Dyne 3500) while serum markers were measured from separated serum using nephelometric analysis (Dade Dimension XRL). Data was analyzed by ANOVA with repeated measures and significant changes (p=0.05) are expressed as means ± SD changes from baseline after 50-days of supplementation for the AA and P groups, respectively. There were no significant group x time interactions in immune markers including white blood cell count (p=0.12), neutrophil count (p=0.17), lymphocyte count (p=0.20) or neutrophil: lymphocyte ratio (p=0.49). There were also no significant group x time interactions with red blood cell count (p=0.49), hemoglobin concentration (p=0.65) or hematocrit % (p=0.79). No significant group x time interactions were evident for liver enzyme levels including alanine aminotransferase (p=0.53) or gamma-glutamyl transferase (p=0.40) nor was there significant a group x time interaction for serum albumin (p=0.43). There was a statistical trend for the decrement in the liver enzyme aspartate aminotransferase in the P group (AA: 4.0 ± 11.2 U/L; P: -10.5 ± 27.7 U/L, p=0.07) but values remained well-within normal limits. No significant group x time interactions were evident for kidney function and/or catabolic indicators including blood urea nitrogen (BUN; p=0.21), creatinine (p=0.41) or BUN:creatinine ratio (p=0.41). None of the thirty-one subjects reported any adverse side effects over the 50-day trial. These results suggest that AA supplementation during an extended period of resistance training is physiologically well-tolerated and does not alter whole blood, liver or kidney clinical safety markers.
SAFETY: Immune System #1
Lipids. 1998 Feb;33(2):125-30.
Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men.
Kelley DS, Taylor PC, Nelson GJ, Mackey BE.
United States Department of Agriculture, Agricultural Research Service, Presidio of San Francisco, California 94129, USA. Dkelley@whnrc.usda.gov
This study was conducted to determine the effects of arachidonic acid (AA) supplementation on human immune response (IR) and on the secretion of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4). Ten healthy men (20-38 yr) participated in the study and lived at the Metabolic Suite of the Western Human Nutrition Research Center. They were fed a basal diet (57, 27, and 16 energy percentage from carbohydrate, fat, and protein, respectively, and AA 200 mg/d) for the first 15 d of the study. Additional AA (1.5 g/d) was added to the diet of six men from day 16 to 65, while the remaining four subjects remained on the basal diet. The diets of the two groups were crossed-over from day 66 to 115. In vitro indices of IR were examined using blood drawn on days 15, 58, 65, 108, and 115. Influenza antibody titers were determined in the sera prepared from blood drawn on days 92 and 115 (23 d postimmunization). AA supplementation caused significant increases in the in vitro secretion of LTB4, and PGE2, but it did not alter the in vitro secretion of tumor necrosis factor alpha; interleukins 1 beta, 2, 6; and the receptor for interleukin 2. Nor did it change the number of circulating lymphocytes bearing markers for specific subsets (B, T, helper, suppressor, natural killer) and the serum antibody titers against influenza vaccine. The opposing effects of PGE2 and LTB4 may have led to the lack of change in immune functions tested.
SAFETY: Immune System #2
Lipids. 1997 Apr;32(4):449-56.
Effects of dietary arachidonic acid on human immune response.
Kelley DS, Taylor PC, Nelson GJ, Schmidt PC, Mackey BE, Kyle D.
USDA, ARS, Western Human Nutrition Research Center, Presidio of San Francisco, California 94129, USA.
Arachidonic acid (AA) is a precursor of eicosanoids, which influence human health and the in vitro activity of immune cells. We therefore examined the effects of dietary AA on the immune response (IR) of 10 healthy men living at our metabolic suite for 130 d. All subjects were fed a basal diet containing 27 energy percentage (en%) fat, 57 en% carbohydrate, and 16 en% protein (AA, 200 mg/d) for the first and last 15 d of the study. Additional AA (1.5 g/d) was incorporated into the diet of six men from day 16 to 65 while the remaining four subjects continued to eat the basal diet. The diets of the two groups were crossed-over from day 66 to 115. In vitro indexes of IR were examined using the blood samples drawn on days 15, 58, 65, 108, 115, and 127. The subjects were immunized with the measles/mumps/rubella vaccine on day 35 and with the influenza vaccine on day 92. Dietary AA did not influence many indexes of IR (peripheral blood mononuclear cell proliferation in response to phytohemagglutinin, Concanavalin A, pokeweed, measles/mumps/rubella, and influenza vaccines prior to immunization, and natural killer cell activity). The post-immunization proliferation in response to influenza vaccine was about fourfold higher in the group receiving high-AA diet compared to the group receiving low-AA diet (P = 0.02). Analysis of variance of the data pooled from both groups showed that the number of circulating granulocytes was significantly (P = 0.03) more when the subjects were fed the high-AA diet than when they were fed the low-AA diet. The small increases in granulocyte count and the in vitro proliferation in response to influenza vaccine caused by dietary AA may not be of clinical significance. However, the lack of any adverse effects on IR indicates that supplementation with AA may be done safely when needed for other health reasons.
SAFETY: Platelet Aggregation
Lipids. 1997 Apr;32(4):421-5.
The effect of dietary arachidonic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans.
Nelson GJ, Schmidt PC, Bartolini G, Kelley DS, Kyle D.
Western Human Nutrition Research Center, ARS, USDA, San Francisco, California 94129, USA.
Arachidonic acid (AA) is the precursor of thromboxane and prostacyclin, two of the most active compounds related to platelet function. The effect of dietary AA on platelet function in humans is not understood although a previous study suggested dietary AA might have adverse physiological consequences on platelet function. Here normal healthy male volunteers (n = 10) were fed diets containing 1.7 g/d of AA for 50 d. The control diet contained 210 mg/d of AA. Platelet aggregation in the platelet-rich plasma was determined using ADP, collagen, and AA. No statistical differences could be detected between the aggregation before and after consuming the high-AA diet. The prothrombin time, partial thromboplastin time, and the antithrombin III levels in the subjects were determined also. There were no statistically significant differences in these three parameters when the values were compared before and after they consumed the high-AA diet. The in vivo bleeding times also did not show a significant difference before and after the subjects consumed the high-AA diet. Platelets exhibited only small changes in their AA content during the AA feeding period. The results from this study on blood clotting parameters and in vitro platelet aggregation suggest that adding 1.5 g/d of dietary AA for 50 d to a typical Western diet containing about 200 mg of AA produces no observable physiological changes in blood coagulation and thrombotic tendencies in healthy, adult males compared to the unsupplemented diet. Thus, moderate intakes of foods high in AA have few effects on blood coagulation, platelet function, or platelet fatty acid composition.
Lipids. 1997 Apr;32(4):427-33.
The effect of dietary arachidonic acid on plasma lipoprotein distributions, apoproteins, blood lipid levels, and tissue fatty acid composition in humans.
Nelson GJ, Schmidt PC, Bartolini G, Kelley DS, Phinney SD, Kyle D, Silbermann S, Schaefer EJ.
Western Human Nutrition Research Center, ARS, USDA, San Francisco, California 94129, USA.
Normal healthy male volunteers (n = 10) were fed diets (high-AA) containing 1.7 g/d of arachidonic acid (AA) for 50 d. The control (low-AA) diet contained 210 mg/d of AA. Dietary AA had no statistically significant effect on the blood cholesterol levels, lipoprotein distribution, or apoprotein levels. Adipose tissue fatty acid composition was not influenced by AA feeding. The plasma total fatty acid composition was markedly enriched in AA after 50 d (P < 0.005). The fatty acid composition of plasma lipid fractions, cholesterol esters, triglycerides, free fatty acids, and phospholipid (PL) showed marked differences in the degree of enrichment in AA. The PL plasma fraction from the subjects consuming the low-AA diet contained 10.3% AA while the subjects who consumed the high-AA diet had plasma PL fractions containing 19.0% AA. The level of 22:4n-6 also was different (0.67 to 1.06%) in the plasma PL fraction after 50 d of AA feeding. After consuming the high-AA diet, the total red blood cell fatty acid composition was significantly enriched in AA which mainly replaced linoleic acid. These results indicate that dietary AA is incorporated into tissue lipids, but selectively into different tissues and lipid classes. Perhaps more importantly, the results demonstrate that dietary AA does not alter blood lipids or lipoprotein levels or have obvious adverse health effects at this level and duration of feeding.
General, plus AA loading times
New Paper on Arachidonic Acid Supplementation
A paper on the supplementation of arachidonic acid (AA) was recently published in the British Journal of Nutrition (British Journal of Nutrition (2007), 98, 451–453). This article is of interest to the athletic community supplementing arachidonic acid for a number of reasons, most notably its focus on safety, its close examination of the buildup and depletion of arachidonic acid in the body, and its use of AA combined with a high intake of Omega-3 fatty acids. Key to this review was a study published in the same journal in April of 2007 by Kusumoto et al. (Br J Nutr. 2007 Sep;98(3):626-35. Epub 2007 Apr 20), which involved the supplementation of arachidonic acid (840mg/d) in a group of 24 healthy Japanese men that consumed high amounts of fish in their diet. This is the first paper of its kind, as most previous investigations of arachidonic acid supplementation safety involved Westerners with low daily intakes of Omega-3 fatty acids. Habitual daily intakes of DHA and EPA in this study ranged from 42 to 691mg and 98 to 991mg, respectively. The average intakes were about 310mg and 550 mg per day. Among the findings were the following.
2-Week Buildup Window:
It took 2 weeks for maximum arachidonic acid levels to be achieved in serum phospholipids. This was the first study to closely examine the time it took to reach peak levels with AA supplementations, and reinforces anecdotal observations of a 2-3 week “loading” window before significant results are noted with supplementation in bodybuilders/athletes.
Arachidonic acid levels remained elevated for a few weeks after supplementation was discontinued. They reached their pretreated levels after 4 weeks. This may also explain why some continue to notice progress in the immediate weeks following AA discontinuation.
Omega-3’s Had No Effect:
Peak arachidonic acid levels were similar in this study to other studies where AA was given to subjects with low dietary levels of Omega-3 fatty acids. At these levels there did not appear to be any significant Omega-3 antagonism of arachidonic acid. This study reinforces the anecdotal observations that low doses of fish oil or regular fish consumption do not appear to appreciably diminish the results of arachidonic acid supplementation.
Arachidonic Acid Supplementation is Safe:
This paper one again takes a review of the safety of arachidonic acid supplementation, with interest in its effects on many areas of health including inflammation, immune functioning, lipids, blood pressure, platelet aggregation, glucose concentrations, liver function, and bleeding time, and notes that arachidonic acid supplementation appears to be perfectly safe in healthy subjects. When noting the inclusion of the most recent AA study (Kusumoto), the British Journal of Nutrition review states:
“Taken together with earlier studies, this study suggests that, rather than being harmful, moderately increased arachidonic acid intake is probably harmless in healthy adults, although the effect of intakes above 1.5g/d are not known and the effect of increased intake in diseased individuals is not known.”