Association of enterolactone with blood pressure and hypertension risk in NHANES.

The gut microbiome may affect overall cardiometabolic health. Enterolactone is an enterolignan reflective of dietary lignan intake and gut microbiota composition and diversity that can be measured in the urine. The purpose of this study was to examine the association between urinary enterolactone concentration as a reflection of gut health and blood pressure/risk of hypertension in a large representative sample from the US population. This analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) collected from January 1999 through December 2010. Variables of interest included participant characteristics (including demographic, anthropometric and social/environmental factors), resting blood pressure and hypertension history, and urinary enterolactone concentration. 10,637 participants (45 years (SE = 0.3), 51.7% (SE = 0.6%) were female) were included in analyses. In multivariable models adjusted for demographic, socioeconomic and behavioral/environmental covariates, each one-unit change in log-transformed increase in enterolactone was associated with a 0.738 point (95% CI: -0.946, -0.529; p<0.001) decrease in systolic blood pressure and a 0.407 point (95% CI: -0.575, -0.239; p<0.001) decrease in diastolic blood pressure. Moreover, in fully adjusted models, each one-unit change in log-transformed enterolactone was associated with 8.2% lower odds of hypertension (OR = 0.918; 95% CI: 0.892, 0.944; p<0.001). Urinary enterolactone, an indicator of gut microbiome health, is inversely associated with blood pressure and hypertension risk in a nationally representative sample of U.S. adults.

International society of sports nutrition position stand: coffee and sports performance.

Based on review and critical analysis of the literature regarding the contents and physiological effects of coffee related to physical and cognitive performance conducted by experts in the field and selected members of the International Society of Sports Nutrition (ISSN), the following conclusions represent the official Position of the Society:(1) Coffee is a complex matrix of hundreds of compounds. These are consumed with broad variability based upon serving size, bean type (e.g. common Arabica vs. Robusta), and brew method (water temperature, roasting method, grind size, time, and equipment).(2) Coffee's constituents, including but not limited to caffeine, have neuromuscular, antioxidant, endocrine, cognitive, and metabolic (e.g. glucose disposal and vasodilation) effects that impact exercise performance and recovery.(3) Coffee's physiologic effects are influenced by dose, timing, habituation to a small degree (to coffee or caffeine), nutrigenetics, and potentially by gut microbiota differences, sex, and training status.(4) Coffee and/or its components improve performance across a temporal range of activities from reaction time, through brief power exercises, and into the aerobic time frame in most but not all studies. These broad and varied effects have been demonstrated in men (mostly) and in women, with effects that can differ from caffeine ingestion, per se. More research is needed.(5) Optimal dosing and timing are approximately two to four cups (approximately 473-946 ml or 16-32 oz.) of typical hot-brewed or reconstituted instant coffee (depending on individual sensitivity and body size), providing a caffeine equivalent of 3-6 mg/kg (among other components such as chlorogenic acids at approximately 100-400 mg per cup) 60 min prior to exercise.(6) Coffee has a history of controversy regarding side effects but is generally considered safe and beneficial for healthy, exercising individuals in the dose range above.(7) Coffee can serve as a vehicle for other dietary supplements, and it can interact with nutrients in other foods.(8) A dearth of literature exists examining coffee-specific ergogenic and recovery effects, as well as variability in the operational definition of "coffee," making conclusions more challenging than when examining caffeine in its many other forms of delivery (capsules, energy drinks, "pre-workout" powders, gum, etc.).

Saturated Fatty Acids and Omega-3 Polyunsaturated Fatty Acids Improve Metabolic Parameters in Ovariectomized Female Mice.

In menopausal and postmenopausal women, the risk for obesity, cardiovascular disease, osteoporosis, and gut dysbiosis are elevated by the depletion of 17ß-estradiol. A diet that is high in omega-6 polyunsaturated fatty acids (PUFAs), particularly linoleic acid (LA), and low in saturated fatty acids (SFAs) found in coconut oil and omega-3 PUFAs may worsen symptoms of estrogen deficiency. To investigate this hypothesis, ovariectomized C57BL/6J and transgenic fat-1 mice, which lower endogenous omega-6 polyunsaturated fatty acids, were treated with either a vehicle or estradiol benzoate (EB) and fed a high-fat diet with a high or low PUFA:SFA ratio for ~15 weeks. EB treatment reversed obesity, glucose intolerance, and bone loss in ovariectomized mice. fat-1 mice fed a 1% LA diet experienced reduced weight gain and adiposity, while those fed a 22.5% LA diet exhibited increased energy expenditure and activity in EB-treated ovariectomized mice. Coconut oil SFAs and omega-3 FAs helped protect against glucose intolerance without EB treatment. Improved insulin sensitivity was observed in wild-type and fat-1 mice fed 1% LA diet with EB treatment, while fat-1 mice fed 22.5% LA diet was protected against insulin resistance without EB treatment. The production of short-chain fatty acids by gut microbial microbiota was linked to omega-3 FAs production and improved energy homeostasis. These findings suggest that a balanced dietary fatty acid profile containing SFAs and a lower ratio of omega-6:omega-3 FAs is more effective in alleviating metabolic disorders during E2 deficiency.

Exercise enhancement by RGS14 disruption is mediated by brown adipose tissue.

Enhanced exercise capacity is not only a feature of healthful aging, but also a therapy for aging patients and patients with cardiovascular disease. Disruption of the Regulator of G Protein Signaling 14 (RGS14) in mice extends healthful lifespan, mediated by increased brown adipose tissue (BAT). Accordingly, we determined whether RGS14 knockout (KO) mice exhibit enhanced exercise capacity and the role of BAT in mediating exercise capacity. Exercise was performed on a treadmill and exercise capacity was assessed by maximal running distance and work to exhaustion. Exercise capacity was measured in RGS14 KO mice and their wild types (WT), and also in WT mice with BAT transplantation from RGS14 KO mice or from other WT mice. RGS14 KO mice demonstrated 160 ± 9% increased maximal running distance and 154 ± 6% increased work to exhaustion, compared to WT mice. RGS14 KO BAT transplantation to WT mice, resulted in a reversal of phenotype, with the WT mice receiving the BAT transplant from RGS14 KO mice demonstrating 151 ± 5% increased maximal running distance and 158 ± 7% increased work to exhaustion, at three days after BAT transplantation, compared to RGS14 KO donors. BAT transplantation from WT to WT mice also resulted in increased exercise performance, but not at 3 days, but only at 8 weeks after transplantation. The BAT induced enhanced exercise capacity was mediated by (1) mitochondrial biogenesis and SIRT3; (2) antioxidant defense and the MEK/ERK pathway, and increased hindlimb perfusion. Thus, BAT mediates enhanced exercise capacity, a mechanism more powerful with RGS14 disruption.

Microbiota Mediate Enhanced Exercise Capacity Induced by Exercise Training.

PURPOSE: We investigated the effects of gut microbes, and the mechanisms mediating the enhanced exercise performance induced by exercise training, i.e., skeletal muscle blood flow, and mitochondrial biogenesis and oxidative function in male mice. METHODS: All mice received a graded exercise test before (PRE) and after exercise training via forced treadmill running at 60% to 70% of maximal running capacity 5 d·wk -1 for 5 wk (POST). To examine the role of the gut microbes, the graded exercise was repeated after 7 d of access to antibiotic (ABX)-treated water, used to eliminate gut microbes. Peripheral blood flow, mitochondrial oxidative capacity, and markers of mitochondrial biogenesis were collected at each time point. RESULTS: Exercise training led to increases of 60% ± 13% in maximal running distance and 63% ± 11% work to exhaustion ( P < 0.001). These increases were abolished after ABX ( P < 0.001). Exercise training increased hindlimb blood flow and markers of mitochondrial biogenesis and oxidative function, including AMP-activated protein kinase, sirtuin-1, PGC-1α citrate synthase, complex IV, and nitric oxide, all of which were also abolished by ABX treatment. CONCLUSIONS: Our results support the concept that gut microbiota mediate enhanced exercise capacity after exercise training and the mechanisms responsible, i.e., hindlimb blood flow, mitochondrial biogenesis, and metabolic profile. Finally, results of this study emphasize the need to fully examine the impact of prescribing ABX to athletes during their training regimens and how this may affect their performance.

Coconut Oil Saturated Fatty Acids Improved Energy Homeostasis but not Blood Pressure or Cognition in VCD-Treated Female Mice.

Obesity, cardiometabolic disease, cognitive decline, and osteoporosis are symptoms of postmenopause, which can be modeled using 4-vinylcyclohexene diepoxide (VCD)-treated mice to induce ovarian failure and estrogen deficiency combined with high-fat diet (HFD) feeding. The trend of replacing saturated fatty acids (SFAs), for example coconut oil, with seed oils that are high in polyunsaturated fatty acids, specifically linoleic acid (LA), may induce inflammation and gut dysbiosis, and worsen symptoms of estrogen deficiency. To investigate this hypothesis, vehicle (Veh)- or VCD-treated C57BL/6J mice were fed a HFD (45% kcal fat) with a high LA:SFA ratio (22.5%: 8%), referred to as the 22.5% LA diet, or a HFD with a low LA:SFA ratio (1%: 31%), referred to as 1% LA diet, for a period of 23 to 25 weeks. Compared with VCD-treated mice fed the 22.5% LA diet, VCD-treated mice fed the 1% LA diet showed lower weight gain and improved glucose tolerance. However, VCD-treated mice fed the 1% LA diet had higher blood pressure and showed evidence of spatial cognitive impairment. Mice fed the 1% LA or 22.5% LA diets showed gut microbial taxa changes that have been associated with a mix of both beneficial and unfavorable cognitive and metabolic phenotypes. Overall, these data suggest that consuming different types of dietary fat from a variety of sources, without overemphasis on any particular type, is the optimal approach for promoting metabolic health regardless of estrogen status.

Naltrexone alters cardiovascular function following acute forced swimming in mice.

Purpose: Naltrexone (NTX) is an opioid antagonist that can reverse the physiological effects of opioid receptors when bound. Opioid receptors have been found to play a role in cardiovascular (CV) function, and thus, binding of NTX may alter CV activity at rest and in response to acute and chronic exercise (EX). We hypothesized that opioid receptor blockade will alter the typical CV responses following acute EX. Methods: We assessed the effects of opioid receptor blockade on CV function via echocardiography in mice following an acute bout of forced swimming (FSw), a model of rodent EX. We administered opioid receptor antagonist, NTX, or saline in mice before FSw and in the absence of an FSw perturbation. Furthermore, we assessed how NTX can influence maximal EX capacity on a rodent treadmill. Results: Our data shows that NTX administration does not decrease maximal EX capacity in mice (P > 0.05). However, NTX attenuated cardiac output following FSw (FSw = 52.5 ± 2.5 ml/min vs. FSw + NTX = 32.7 ± 5.2 ml/min; P < 0.05) when compared with saline control (33.5 ± 3.8 ml/min). Further, the administration of NTX in the non-EX condition significantly (P < 0.05) reduced ejection fraction. Conclusion: These data suggest that normal opioid receptor activation is necessary for typical CV function following FSw.

"The addition of naltrexone alters cerebral glucose uptake following acute forced swimming".

Endogenous opioid release has been linked to exercise. We investigated if opioid blockade following forced swimming, a common model of rodent exercise, influenced cerebral glucose metabolism in mice. PET scan was used to assess the uptake of Fludeoxyglucose (FDG-18), a marker of cerebral glucose metabolism in 19 regions of the interest in the brain following: forced swimming, an acute dose of the opioid receptor blocker naltrexone or a combination of both. Forced swimming increased glucose uptake in the cerebellum, while naltrexone + forced swimming increased glucose uptake in the hypothalamus, forebrain, septum and amygdala. This suggests that opioid blockade alters the typical pattern of cerebral glucose uptake following forced swimming in mice in certain areas of the brain.

Role of Dietary Lipids in Modulating Inflammation through the Gut Microbiota.

Inflammation and its resolution is a tenuous balance that is under constant contest. Though several regulatory mechanisms are employed to maintain homeostasis, disruptions in the regulation of inflammation can lead to detrimental effects for the host. Of note, the gut and microbial dysbiosis are implicated in the pathology of systemic chronic low-grade inflammation which has been linked to several metabolic diseases. What remains to be described is the extent to which dietary fat and concomitant changes in the gut microbiota contribute to, or arise from, the onset of metabolic disorders. The present review will highlight the role of microorganisms in host energy regulation and several mechanisms that contribute to inflammatory pathways. This review will also discuss the immunomodulatory effects of the endocannabinoid system and its link with the gut microbiota. Finally, a brief discussion arguing for improved taxonomic resolution (at the species and strain level) is needed to deepen our current knowledge of the microbiota and host inflammatory state.

Effects of ovariectomy and exercise training intensity on energy substrate and hepatic lipid metabolism, and spontaneous physical activity in mice.

BACKGROUND: Menopause is associated with fatty liver, glucose dysregulation, increased body fat, and impaired bone quality. Previously, it was demonstrated that single sessions of high-intensity interval exercise (HIIE) are more effective than distance- and duration-matched continuous exercise (CE) on altering hepatic triglyceride (TG) metabolism and very-low density lipoprotein-TG (VLDL-TG) secretion. METHODS: Six weeks training using these modalities was examined for effects on hepatic TG metabolism/secretion, glucose tolerance, body composition, and bone mineral density (BMD) in ovariectomized (OVX) and sham-operated (SHAM) mice. OVX and SHAM were assigned to distance- and duration-matched CE and HIIE, or sedentary control. RESULTS: Energy expenditure during exercise was confirmed to be identical between CE and HIIE and both similarly reduced post-exercise absolute carbohydrate oxidation and spontaneous physical activity (SPA). OVX vs. SHAM displayed impaired glucose tolerance and greater body fat despite lower hepatic TG, and these outcomes were not affected by training. Only HIIE increased hepatic AMPK in OVX and SHAM, but neither training type impacted VLDL-TG secretion. As expected, BMD was lower in OVX, and training did not affect long bones. CONCLUSIONS: The results reveal intensity-dependent effects on hepatic AMPK expression and general exercise effects on subsequent SPA and substrate oxidation that is independent of estrogen status. These findings support the notion that HIIE can impact aspects of liver physiology in females while the effects of exercise on whole body substrate selection appear to be independent of training intensity. However, neither exercise approach mitigated the impairment in glucose tolerance and elevated body fat occurring in OVX mice.

Disruption of adenylyl cyclase type 5 mimics exercise training.

Exercise training is key to healthful longevity. Since exercise training compliance is difficult, it would be useful to have a therapeutic substitute that mimicked exercise training. We compared the effects of exercise training in wild-type (WT) littermates with adenylyl cyclase type 5 knock out (AC5 KO) mice, a model of enhanced exercise performance. Exercise performance, measured by maximal distance and work to exhaustion, was increased in exercise-trained WT to levels already attained in untrained AC5 KO. Exercise training in AC5 KO further enhanced their exercise performance. The key difference in untrained AC5 KO and exercise-trained WT was the ß-adrenergic receptor signaling, which was decreased in untrained AC5 KO compared to untrained WT but was increased in WT with exercise training. Despite this key difference, untrained AC5 KO and exercise-trained WT mice shared similar gene expression, determined by deep sequencing, in their gastrocnemius muscle with 183 genes commonly up or down-regulated, mainly involving muscle contraction, metabolism and mitochondrial function. The SIRT1/PGC-1α pathway partially mediated the enhanced exercise in both AC5 KO and exercise-trained WT mice, as reflected in the reduced exercise responses after administering a SIRT1 inhibitor, but did not abolish the enhanced exercise performance in the AC5 KO compared to untrained WT. Increasing oxidative stress with paraquat attenuated exercise performance more in untrained WT than untrained AC5 KO, reflecting the augmented oxidative stress protection in AC5 KO. Blocking nitric oxide actually reduced the enhanced exercise performance in untrained AC5 KO and trained WT to levels below untrained WT, demonstrating the importance of this mechanism. These results suggest that AC5 KO mice, without exercise training, share similar mechanisms responsible for enhanced exercise capacity with chronic exercise training, most importantly increased nitric oxide, and demonstrate more reserve with the addition of exercise training. A novel feature of the enhanced exercise performance in untrained AC5 KO mice is their decreased sympathetic tone, which is also beneficial to patients with cardiovascular disease.

Microbes and mental health: A review.

There is a growing emphasis on the relationship between the microorganisms inhabiting the gut (gastrointestinal microbiota) and human health. The emergence of a microbiota-gut-brain axis to describe the complex networks and relationship between the gastrointestinal microbiota and host reflects the major influence this environment may have in brain health and disorders of the central nervous system (CNS). Bidirectional communication between the microbiota and the CNS occurs through autonomic, neuroendocrine, enteric, and immune system pathways. Potential neurobiological mechanisms through which disruptions in this network may impact health and disease include hypothalamic-pituitary-adrenal (HPA)-axis activation, and altered activity of neurotransmitter and immune systems. Perturbations of the gut microbial community have already been implicated in multiple host diseases such as obesity, diabetes, and inflammation, while recent evidence suggests a potential role of the microbiota-gut-brain axis in neuropsychiatric disorders, such as depression and anxiety. Here, we review the current literature related to the influence of the gut microbial community on central nervous system function, with a specific focus on anxiety and depressive symptoms. The role of stress and stress-mediated changes in autonomic, neuroendocrine, immune, and neurotransmitter systems are examined, followed by a discussion of the role of the microbiota in novel gastrointestinal-based treatment options for the prevention and treatment of brain-based disorders such as anxiety and depression.

Exercise is a Novel Promoter of Intestinal Health and Microbial Diversity.

Imbalances in the gut microbiota contribute to chronic gut inflammatory diseases. Interestingly, exercise can improve gut health, but generally, little is known about the underlying mechanisms involved. This article represents a conceptual model illustrating exercise's role in diversifying the gut microbiota to improve gut and systemic health.

The Effects of Supplementation with p-Synephrine Alone and in Combination with Caffeine on Metabolic, Lipolytic, and Cardiovascular Responses during Resistance Exercise.

OBJECTIVE: The purpose of this study was to examine the metabolic, lipolytic, and cardiovascular responses to supplementation with p-synephrine alone and in combination with caffeine during resistance exercise (RE). METHODS: Twelve healthy men performed a control RE protocol (6 × 10 repetitions of squats) and were randomly assigned (using a double-blind crossover design with random protocol sequencing) to a supplement sequence: p-synephrine (S; 100 mg), p-synephrine + caffeine (SCF; 100 mg of p-synephrine plus 100 mg of caffeine), or a placebo (P). Subjects reported to the lab at a standard time, consumed a supplement, sat quietly for 45 minutes, performed the RE protocol, and sat quietly for 30 minutes. Blood samples were collected at rest (T1), after sitting quietly for 45 minutes (T2), immediately following RE (T3), and 15 minutes (T4) and 30 minutes (T5) postexercise. Oxygen consumption (VO2) and heart rate (HR) data were collected throughout. RESULTS: Serum glycerol was significantly elevated at T2 only in S and SCF and T3 to T5 in all treatments. Nonesterified fatty acid (NEFA) concentrations did not differ between treatments. Plasma glucose was significantly elevated compared to T1 with highest area under the curve values seen in SCF. Mean VO2 and energy expenditure (EE) were significantly higher in S and SCF through 30 minutes postexercise. Fat oxidation rates favored S and SCF between 25 and 30 minutes postexercise. Mean HR during RE was significantly highest in SCF. CONCLUSIONS: Supplementation with S and SCF increases lipolysis primarily at rest and increases VO2, EE, and fat oxidation rates 30 minutes following RE. No HR changes were observed unless caffeine was added.

The Effect of Diet and Exercise on Intestinal Integrity and Microbial Diversity in Mice.

BACKGROUND: The gut microbiota is now known to play an important role contributing to inflammatory-based chronic diseases. This study examined intestinal integrity/inflammation and the gut microbial communities in sedentary and exercising mice presented with a normal or high-fat diet. METHODS: Thirty-six, 6-week old C57BL/6NTac male mice were fed a normal or high-fat diet for 12-weeks and randomly assigned to exercise or sedentary groups. After 12 weeks animals were sacrificed and duodenum/ileum tissues were fixed for immunohistochemistry for occludin, E-cadherin, and cyclooxygenase-2 (COX-2). The bacterial communities were assayed in fecal samples using terminal restriction fragment length polymorphism (TRFLP) analysis and pyrosequencing of 16S rRNA gene amplicons. RESULTS: Lean sedentary (LS) mice presented normal histologic villi while obese sedentary (OS) mice had similar villi height with more than twice the width of the LS animals. Both lean (LX) and obese exercise (OX) mice duodenum and ileum were histologically normal. COX-2 expression was the greatest in the OS group, followed by LS, LX and OX. The TRFLP and pyrosequencing indicated that members of the Clostridiales order were predominant in all diet groups. Specific phylotypes were observed with exercise, including Faecalibacterium prausnitzi, Clostridium spp., and Allobaculum spp. CONCLUSION: These data suggest that exercise has a strong influence on gut integrity and host microbiome which points to the necessity for more mechanistic studies of the interactions between specific bacteria in the gut and its host.

A combination of Scutellaria baicalensis and Acacia catechu extracts for short-term symptomatic relief of joint discomfort associated with osteoarthritis of the knee.

The extracts of Scutellaria baicalensis and Acacia catechu have been shown in previous studies to alleviate joint discomfort, reduce stiffness, and improve mobility by reducing the production of proinflammatory molecules over long periods of supplementation. The acute effects of intake of these extracts have not yet been investigated. Thus, we carried out a 1 week clinical trial to examine the extent to which UP446-a natural proprietary blend of S. baicalensis and A. catechu (UP446)-decreases knee joint pain, mobility, and biomarkers of inflammation in comparison to naproxen. Seventy-nine men and women (40-90 years old) diagnosed as having mild to moderate osteoarthritis (OA) consumed either 500 mg/day of the UP446 supplement or 440 mg/day of naproxen for 1 week in a double-blind randomized control trial. Pain, knee range of motion (ROM), and overall physical activity were evaluated at the start and at the end of treatment. Fasting blood was collected to determine serum interleukins 1ß and 6, tumor necrosis factor-α, C-reactive protein, and hyaluronic acid. The UP446 group experienced a significant decrease in perceived pain (P=.009) time dependently. Stiffness was significantly reduced by both treatments (P=.002 UP446, P=.008 naproxen). Significant increases in mean ROM over time (P=.04) were found in the UP446 group. These findings suggest that UP446 is effective in reducing the physical symptoms associated with knee OA.

Biocompatibility and microstructural analysis of osteopromotive property of allogenic demineralized dentin matrix.

PURPOSE: Bone grafting materials and methods have been used to compensate anatomical limitations and improve ridge and sinus structure for implant placement. The objective of this study was to evaluate the osteopromotive property of allogenic demineralized dentin matrix (DDM) as a bone grafting material using micro-computed tomography and blood biomarkers. MATERIALS AND METHODS: Two surgical bone defects were created on the skull of 30 female New Zealand White rabbits. Experimental defects in 24 rabbits were filled with allogenic DDM applying guided bone regeneration technique, while the control defects were covered by membrane without receiving the graft. In the remaining six rabbits, both defects were left empty and these rabbits served as control for blood biomarkers. The 24 experimental rabbits were sacrificed after 15, 30, 60, and 90 days (n = 6 at each time point). Blood samples were collected from all rabbits at the baseline, 48 hours postsurgery, and at each time point. RESULTS: Bone thickness was significantly higher in the experimental group at all time points. Micro-computed tomography results showed increased bone mass and superior bone quality in the experimental group. At all time points except for 48 hours postsurgery, the white blood cell count was numerically higher in control rabbits compared to experimental rabbits, suggesting a lack of inflammation or infection due to allogenic DDM. Bone-specific alkaline phosphatase activities were lower in both experimental and control groups at all time points in comparison to baseline values, which is indicative of either a lower rate of bone formation or bone turnover. CONCLUSIONS: Within the limitations of this study, allogenic demineralized dentin matrix significantly increased bone mass and improved bone quality without causing an inflammatory reaction or infection.

Flaxseed reverses atherosclerotic lesion formation and lowers lipoprotein(a) in ovarian hormone deficiency.

OBJECTIVE: The incidence of cardiovascular disease dramatically increases during menopause, and postmenopausal women seek natural alternatives to hormone therapy. Flaxseed can slow the progression of atherosclerotic lesion formation; however, it is not known whether it can reverse formation that has already occurred. METHODS: Seventy-two female Golden Syrian hamsters were randomly divided into six groups (n = 12), sham-operated (sham) or ovariectomized (ovx), and kept on the same diet for 120 days to allow for atherosclerotic lesion development. After this 120-day period, whole flaxseed was introduced to the diets of hamsters in three of the groups: group 1 (sham + casein); group 2 (ovx + casein); group 3 (ovx + 7.5% flaxseed); group 4 (ovx + 15% flaxseed); group 5 (ovx + 22.5% flaxseed); and group 6 (ovx + 17ß-estradiol). This diet was maintained for an additional 120 days. Lesion regression was examined histologically, and serum was analyzed for total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, Apo A, Apo B, and lipoprotein(a). RESULTS: Results showed that 15% and 22.5% flaxseed, compared with ovx animals, significantly reduced lipoprotein(a) (4.4 mg/dL [ovx] vs 2.15 mg/dL [15% flaxseed] and 0.3 mg/dL [22.5% flaxseed]; P < 0.05) and Apo B (2.8 mg/dL [ovx] vs 2.4 mg/dL [15% flaxseed] and 2.5 mg/dL [22.5% flaxseed]). Flax reduced by 67% the number of animals with aortic arch lesions. CONCLUSIONS: All three doses of flax reduce the severity of lesion formation compared with ovx controls. These results support the efficacy of flaxseed in reducing cardiovascular disease risk.