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Papers by Ryan Wood-Bradley

Journal of Nutrigenetics and Nutrigenomics, 2015

Observational research associating 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms... more Observational research associating 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms with risk of autism, depression, cancer, and cardiovascular disease has led to increased diagnoses of MTHFR; however, doctors lack knowledge about safety, effectiveness, and clinical implications of MTHFR treatment. Treatment strategies are hypothetical and mechanistically based, including methylfolate with or without other B vitamins. This study was designed to formally describe patient and health care provider experiences with the diagnosis and clinical management of MTHFR. Guided by a structured interview guide, a qualitative study queried patients' and providers' observations regarding: testing indications, reaction to results, treatment protocols, and clinical response including adverse effects. Thirty patients and 8 doctors participated. Patient themes included emotionality associated with diagnosis, classification of signs and symptoms, and challenges with treatment. They expressed confusion over their diagnosis, and frustration with the state of knowledge their providers had regarding MTHFR. Testing indications included: fatigue (21%), hormone imbalances (13%), and neurological symptoms (13%) including brain fog (8%). Patients reported improvements in physical (60%) and mental/behavioral symptoms (36%) following treatment. A minority of participants reported side effects, but they occurred in almost every body system and ranged in severity. Doctors relied on trial and error to determine treatment doses, frequency and components. MTHFR testing results in variable clinical processes in domains related to delivery of diagnosis and prognosis, and therapeutic options. However, patients report largely positive experiences. Clinicians and patients would benefit from therapeutic algorithms based on rigorous research.

Integrative medicine

Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are the well-established s... more Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are the well-established standards by which clinicians identify individuals at risk for coronary artery disease (CAD), yet nearly 50% of people who have a myocardial infarction have normal cholesterol levels. Measurement of additional biomarkers may be useful to more fully stratify patients according to disease risk. The typical lipid panel includes TC, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs). Emerging biomarkers for cardiovascular risk include measures of LDL-C pattern, size, and density; LDL particle number; lipoprotein(a); apolipoproteins (apoA1 and apoB100 being the most useful); C-reactive protein; and lipoprotein-associated phospholipase A(2). Some of these emerging biomarkers have been proven to add to, or be more accurate than, traditional risk factors in predicting coronary artery disease and, thus, may be useful for clinical decision-making in high-risk patients and ...

Objectives: We seek to represent the general landscape and outcomes of clinical studies of naturo... more Objectives: We seek to represent the general landscape and outcomes of clinical studies of naturopathic practice, with research intervention models consistent with naturopathic whole practice (rather than single therapeutic modalities) including observational studies in licensed No. American naturopathic medicine to generate hypotheses for further study and to identify gaps in knowledge. Conclusions: Formal whole practice studies in naturopathic medicine are a recent phenomenon in No. America. All studies meeting criteria showed signals of benefit, sometimes quite strong, but also have methodological weaknesses. The review provides evidence of effectiveness and cost savings in chronic diseases in the observed or validity-modeled practice of trained and licensed naturopathic doctors.

Reproductive Biology and Endocrinology, 2015

The placenta is an essential organ that provides nutrients and oxygen to the developing fetus and... more The placenta is an essential organ that provides nutrients and oxygen to the developing fetus and removes toxic waste products from the fetal circulation. Maintaining placental blood osmotic pressure and blood flow is crucial for viable offspring. The renin-angiotensin system (RAS) in the placenta is a key player in the regulation of maternal-fetal blood flow during pregnancy. Therefore, the aim of this study was to determine if RAS genes are differentially expressed in mid to late gestation in rat placenta. Whole placental tissue samples from pregnant Sprague Dawley rats at embryonic (E) days 14.25, 15.25, 17.25 and 20 (n = 6 for each gestational age) were used for genome-wide gene expression by microarray. RAS genes with expression differences of >2 fold were further analyzed. Quantitative Real-Time PCR (qPCR) was performed on independent samples to confirm and validate microarray data. Immunohistochemisty and Western blotting were performed on a differentially expressed novel RAS pathway gene (ANPEP). Six out of 17 genes of the RAS pathway were differentially expressed at different gestational ages. Gene expression of four genes (Angiotensin converting enzyme (Ace), angiotensin converting enzyme 2 (Ace2), membrane metalloendopeptidase (Mme) and angiotensin II receptor 1A (Agtr1a)) were significantly upregulated at E20 whereas two others (Thimet oligopeptidase 1 (Thop1) and Alanyl aminopeptidase (Anpep)) were downregulated at E20 prior to the onset of labour. These changes were confirmed by qPCR. Western blots revealed no overall differences in ANPEP protein expression in the placentae. Immunohistochemical studies, however, indicated that the localization of ANPEP differed at E17.25 and E20 as ANPEP localization in the giant trophoblast cell of the junctional zone was no longer detectable at E20. The current study investigated the expression of members of the RAS pathway in rat placentae and observed significantly altered expression of 6 RAS genes at 4 gestational ages. These findings present the need for further comprehensive investigation of RAS genes in normal and complicated pregnancies.

Integrative Medicine Research, 2015

Mediators of Inflammation, 2015

Mammalian placentation is a vital facet of the development of a healthy and viable offspring. Thr... more Mammalian placentation is a vital facet of the development of a healthy and viable offspring. Throughout gestation the placenta changes to accommodate, provide for, and meet the demands of a growing fetus. Gestational gene expression is a crucial part of placenta development. The endocannabinoid pathway is activated in the placenta and decidual tissues throughout pregnancy and aberrant endocannabinoid signaling during the period of placental development has been associated with pregnancy disorders. In this study, the gene expression of eight endocannabinoid system enzymes was investigated throughout gestation. Rat placentae were obtained at E14.25, E15.25, E17.25, and E20, RNA was extracted, and microarray was performed. Gene expression of enzymes Faah, Mgll, Plcd4, Pld1, Nat1, Daglα, and Ptgs2 was studied (cohort 1, microarray). Biological replication of the results was performed by qPCR (cohort 2). Four genes showed differential expression (Mgll, Plcd4, Ptgs2, and Pld1), from mid to late gestation. Genes positively associated with gestational age were Ptgs2, Mgll, and Pld1, while Plcd4 was downregulated. This is the first comprehensive study that has investigated endocannabinoid pathway gene expression during rat pregnancy. This study provides the framework for future studies that investigate the role of endocannabinoid system during pregnancy.

Food Chemistry, 2015

A novel paper-based Nanoceria Reducing Antioxidant Capacity (NanoCerac) assay for antioxidant det... more A novel paper-based Nanoceria Reducing Antioxidant Capacity (NanoCerac) assay for antioxidant detection (Sharpe, Frasco, Andreescu, & Andreescu, 2012), has been adapted for the first time as a high-throughput method, in order to measure the effect of brewing conditions and re-infusion on the antioxidant capacity of twenty-four commercial green teas. The oxygen radical absorbance capacity (ORAC) assay, frequently applied to complex foods and beverages, was used as a comparator measure of antioxidant capacity. A novel measure of sustained antioxidant capacity, the total inherent antioxidant capacity (TI-NanoCerac and TI-ORAC) was measured by infusing each tea six times. Effects of brewing conditions (temperature, brew time, etc.) were assessed using one popular tea as a standard. Both NanoCerac and ORAC assays correlated moderately (R(2) 0.80±0.19). The average first-brew NanoCerac, TI-NanoCerac, first-brew ORAC and TI-ORAC were: 0.73±0.1GAE/g tea; 2.4±0.70mmolGAE/g tea; 1.0±0.3mmolTE/g tea and 2.1±0.71mmolTE/g tea respectively. Brewing conditions including water temperature and infusion time significantly affected antioxidant capacity. The high-throughput adaptation of the original NanoCerac assay tested here offered advantages over ORAC, including portability and rapid analysis.

Nutrients, 2015

The leading causes of mortality and morbidity worldwide are cardiovascular disease (high blood pr... more The leading causes of mortality and morbidity worldwide are cardiovascular disease (high blood pressure, high cholesterol and renal disease), cancer and diabetes. It is increasingly obvious that the development of these diseases encompasses complex interactions between adult lifestyle and genetic predisposition. Maternal malnutrition can influence the fetal and early life environment and pose a risk factor for the future development of adult diseases, most likely due to impaired organogenesis in the developing offspring. This then predisposes these offspring to cardiovascular disease and renal dysfunction in adulthood. Studies in experimental animals have further illustrated the significant impact maternal diet has on offspring health. Many studies report changes in kidney structure (a reduction in the number of nephrons in the kidney) in offspring of protein-deprived dams. Although the early studies suggested that increased blood pressure was also present in offspring of protein-re...

Global Advances in Health and Medicine, 2013

Interest in case studies has undergone a resurgence concurrent with increasing prioritization of ... more Interest in case studies has undergone a resurgence concurrent with increasing prioritization of illustrations of patient-centered care. However, substantial inclusion of the patient in these reports remains limited. Here, a doctor and patient collaborate to present her case report of self-directed mindfulness training and the subsequent changes in blood pressure, migraine frequency, and quality of life. After receiving encouragement from her naturopathic doctor, the patient initiated an 8-week program in mindfulness training following the Kabat-Zinn protocol and logged her daily blood pressure and symptoms before and after meditation sessions over an 11-week period. Patient-reported outcomes included decreased perceived stress, increased focus, and a newfound sense of centeredness and calm. Changes in objective outcomes were clinically and statistically significant, including reductions in mean systolic and diastolic blood pressure between week 1 and week 11 (P = .0001 and P = .0004 for systolic and diastolic, respectively, by paired, 2-sided t-tests). Self-reported frequency of chronic migraine was also reduced. Critical to the patient's success was that mindfulness training was first approached in a simple, accessible manner prior to embarking on a deeper, extended experience. Self-directed mindfulness training can have a meaningful impact on both subjective and objective health outcomes. It may take years of encouragement from a healthcare provider before a patient is ready to adopt a mind-body practice; it is important to recognize and counsel patients with messages appropriate to their stage of change and self-efficacy. Additionally, case studies that combine the voice of the clinician and the patient can provide useful illustrations of truly patient-centered care.

Biodemography and Social Biology, 2014

The purpose of this study was to examine biological and behavioral explanations for gender differ... more The purpose of this study was to examine biological and behavioral explanations for gender differences in leukocyte telomere length (LTL), a biomarker of cell aging that has been hypothesized to contribute to women's greater longevity. Data are from a subsample (n = 851) of the Multi-Ethnic Study of Atherosclerosis, a population-based study of women and men aged 45 to 84. Mediation models were used to examine study hypotheses. We found that women had longer LTL than men, but the gender difference was smaller at older ages. Gender differences in smoking and processed meat consumption partially mediated gender differences in telomere length, whereas gender differences in estradiol, total testosterone, oxidative stress, and body mass index did not. Neither behavioral nor biological factors explained why the gender difference in LTL was smaller at older ages. Longitudinal studies are needed to assess gender differences in the rate of change in LTL over time; to identify the biological, behavioral, and psychosocial factors that contribute to these differences throughout the life course; and to determine whether gender differences in LTL explain the gender gap in longevity.

The placenta plays a central role in determining the outcome of pregnancy. It undergoes changes d... more The placenta plays a central role in determining the outcome of pregnancy. It undergoes changes during gestation as the fetus develops and as demands for energy substrate transfer and gas exchange increase. The molecular mechanisms that coordinate these changes have yet to be fully elucidated. The study performed a large scale screen of the transcriptome of the rat placenta throughout mid-late gestation (E14.25-E20) with emphasis on characterizing gestational age associated changes in the expression of genes invoved in angiogenic pathways. Sprague Dawley dams were sacrificed at E14.25, E15.25, E17.25 and E20 (n = 6 per group) and RNA was isolated from one placenta per dam. Changes in placental gene expression were identifed using Illumina Rat Ref-12 Expression BeadChip Microarrays. Differentially expressed genes (.2fold change, ,1% false discovery rate, FDR) were functionally categorised by gene ontology pathway analysis. A subset of differentially expressed genes identified by microarrays were confirmed using Real-Time qPCR. The expression of thirty one genes involved in the angiogenic pathway was shown to change over time, using microarray analysis (22 genes displayed increased and 9 gene decreased expression). Five genes (4 up regulated: Cd36, Mmp14, Rhob and Angpt4 and 1 down regulated: Foxm1) involved in angiogenesis and blood vessel morphogenesis were subjected to further validation. qPCR confirmed late gestational increased expression of Cd36, Mmp14, Rhob and Angpt4 and a decrease in expression of Foxm1 before labour onset (P,0.0001). The observed acute, pre-labour changes in the expression of the 31 genes during gestation warrant further investigation to elucidate their role in pregnancy.

Journal of nutritional science, 2013

The high fat content in Western diets probably affects placental function during pregnancy with p... more The high fat content in Western diets probably affects placental function during pregnancy with potential consequences for the offspring in the short and long term. The aim of the present study was to compare genome-wide placental gene expression between rat dams fed a high-fat diet (HFD) and those fed a control diet for 3 weeks before conception and during gestation. Gene expression was measured by microarray and pathway analysis was performed. Gene expression differences were replicated by real-time PCR and protein expression was assessed by Western blot analysis. Placental and fetal weights at E17.25 were not altered by exposure to the maternal HFD. Gene pathways targeting placental growth, blood supply and chemokine signalling were up-regulated in the placentae of dams fed the HFD. The up-regulation in messenger RNA expression for five genes Ptgs2 (fatty acid cyclo-oxidase 2; COX2), Limk1 (LIM domain kinase 1), Pla2g2a (phospholipase A2), Itga1 (integrin α-1) and Serpine1 was co...

The International Journal of Biochemistry & Cell Biology, 2012

Adipocyte Obesity Adipose tissue metabolism Obesity related hypertension Developmental programmin... more Adipocyte Obesity Adipose tissue metabolism Obesity related hypertension Developmental programming of health and disease a b s t r a c t Globally 30% of adults are overweight or obese. The white adipocyte is a major component of adipose tissue, and as the obesity epidemic increases it is critically important to understand the factors determining adipocyte development and function. Adipogenesis has two distinct phases; determination of the adipocyte from a multipotent stem cell, and terminal differentiation of a pre-adipocyte into a mature adipocyte. The environment encountered in early life can alter adipocyte number and size and potentially impact upon adipocyte endocrine function in adulthood. These alterations may contribute to the pathophysiology of chronic diseases and thus targeted therapy of the adipocyte has great potential for treating the current obesity epidemic.

PLoS ONE, 2012

Differences in the effectiveness of diverse healthcare providers to promote health behavior chang... more Differences in the effectiveness of diverse healthcare providers to promote health behavior change and successful diabetes self-care have received little attention. Because training in naturopathic medicine (NM) emphasizes a patient-centered approach, health promotion, and routine use of clinical counseling on wellness and prevention, naturopathic physicians (NDs) may be particularly well-prepared for promoting behavior change. However, patients' experiences with NM have not been well studied. This study provides the first report of the perceptions of persons with type 2 diabetes of their first experiences with naturopathic care for their diabetes. Following their participation in a one-year prospective cohort study of adjunctive naturopathic care for diabetes, twenty-two patients were interviewed about their experiences working with a naturopathic physician. Using a content analysis approach, nine dominant themes were identified. Three themes characterized the nature of the ND-patient interaction: 1) patient-centered, 2) holistic health rather than diabetes focused, and 3) collaborative. Five themes characterized the content of the clinical encounter: 1) individualized and detailed health promotion, 2) counseling that promoted self-efficacy, 3) pragmatic and practical self-care recommendations, 4) novel treatment options that fostered hopefulness, and 5) patient education that addressed both diabetes self-care and general health. A ninth theme was cross-cutting: the contrast between ND care and conventional medical care. Results indicate that the routine clinical approach used by NDs is consistent with behavior change theory and clinical strategies found most effective in promoting self-efficacy and improving clinical outcomes.

Medical Anthropology Quarterly, 2012

Building on a dialogue between three trained naturopaths and a proponent of critical medical anth... more Building on a dialogue between three trained naturopaths and a proponent of critical medical anthropology (CMA), this article highlights the relationship between health and society from the viewpoint of two fields that share this focal concern. Both naturopathy and CMA are committed to the notion of holistic health, although their approaches have historically been somewhat different. The responses of the three naturopaths to CMA exhibit both similarities and differences, particularly in terms of insights that CMA may make to naturopathy. This essay also articulates the CMA perspective of naturopathy and posits lessons that naturopathy can teach CMA.

Journal of Hypertension, 2012

ABSTRACT Background: Maternal obesity may programme the development of hypertension and renal dis... more ABSTRACT Background: Maternal obesity may programme the development of hypertension and renal disease in offspring. It is not known whether high saturated fat intake in pregnancy in the absence of maternal obesity is deleterious to offspring cardiovascular health. Aims: To determine whether excessive maternal fat intake in pregnancy and suckling programmes renal and cardiovascular disease in adult offspring. Methods: Female Sprague-Dawley rats (n = 5-8) were fed a control (C) or high saturated-fat (HF) diet for 3 weeks before mating, during pregnancy and lactation. From weaning, offspring were chow fed ad libitum. At 6 and 12 months of age glomerular filtration rate (GFR) and effective renal blood flow (eRBF) were estimated in anaesthetized rats by [3H]-inulin and [14C]-para-aminohippurate clearance. Mean arterial pressure (MAP) and heart rate were determined by radiotelemetry. Data were analysed by two-way ANOVA. Results: Maternal fat intake did not significantly alter offspring renal or cardiovascular function at 6 months. MAP was significantly elevated in 1 year-old HF offspring (OHF male; 98.8 +/- 3.6, female 101.9 +/- 3.3 compared with controls (OC male; 90.7 +/- 2.7 mmHg, female 90.1 +/- 3.3 mmHg, P<0.05). There was no significant effect of maternal diet on GFR or sodium reabsorption but OHF males had greater eRBF (4.95 +/- 0.44 ml/min/gkw) than OC (2.88 +/- 0.67 ml/min/gkw, P<0.05). eRBF in OHF females (4.6 +/- 1.5 ml/min/gkw) was significantly less than OC (7.7 +/- 1.9 ml/min/gkw, P<0.05). Conclusions: Maternal diets high in saturated fat can programme hypertension and sexually dimorphic alterations in renal haemodynamics in offspring.

The Journal of Clinical Endocrinology & Metabolism, 2014

As a result of research suggesting increased health risk with low serum 25-hydroxycholecalciferol... more As a result of research suggesting increased health risk with low serum 25-hydroxycholecalciferol (25(OH)D), health care providers are measuring it frequently. Providers and patients are faced with treatment choices when low status is identified. To compare the safety and efficacy of three vitamin D3 dietary supplements with different delivery matrices. A 12-week, parallel group, single-masked, clinical trial was conducted in Seattle, Washington and Kailua Kona, Hawaii. Sixty-six healthy adults with (25(OH)D) <33 ng/mL were randomly assigned to take one of three D3 supplements, ie, a chewable tablet (TAB), an oil-emulsified drop (DROP), or an encapsulated powder (CAP) at a label-claimed dose of 10,000 IU/day. Actual D3 content was assessed by a third party and the results adjusted based on the actual D3 content administered. Mean change in 25(OH)D/mcg D3 administered; difference in the proportion of D3 insufficient participants (ie, 25(OH)D ≤30 ng/mL) reaching sufficiency (ie, 25(OH)D ≥30 ng/mL); and mean change in serum 1, 25-dihydroxycholecalciferol were measured. In two of the three products tested, the measured vitamin D3 content varied considerably from the label-claimed dose. Differences in 25(OH)D/mcg D3 administered were significantly different between groups (P = .04; n = 55). Pairwise comparisons demonstrated DROP resulted in a greater increase than TAB (P < .05) but not than CAP. TAB was not different from CAP. The proportions reaching sufficiency were: 100% (TAB and CAP) and 80% (DROP) (P = .03 between groups; n = 55). 1, 25-Dihydroxycholecalciferol did not change significantly in any group. Oil-emulsified vitamin D3 supplements resulted in a greater mean change in serum 25(OH)D concentration, but fewer patients reaching vitamin D sufficiency, than chewable or encapsulated supplements.

The Journal of Alternative and Complementary Medicine, 2014

The Journal of Alternative and Complementary Medicine, 2009

Background: Survey findings report that 48% of people with type 2 diabetes use complementary and ... more Background: Survey findings report that 48% of people with type 2 diabetes use complementary and alternative medicine (CAM) practice. Publications suggest a high incidence of health promotion counseling in naturopathic practice, yet clinical data on risk factor changes are not available in the literature. Objectives: The primary aim of this study was to describe clinical risk factor changes during the utilization of naturopathic CAM services in patients with type 2 diabetes. Design: A retrospective, observational study design was used to describe naturopathic care. Setting: Abstracted medical charts were from patients of the Bastyr Center for Natural Health in Seattle, WA. Participants: The patients in this study had type 2 diabetes and received naturopathic care between 2001 and 2006. Outcomes: Abstracted data included patient demographics, duration of care, number of visits, laboratory values for hemoglobin A1c (HbA1c), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol, triglycerides (TAG); and systolic=diastolic blood pressure (SPB, DBP). Results: Thirty-seven (37) patient records met inclusion criteria and were abstracted in detail. Mean and median duration of care were 27 and 20 months, respectively. The mean number of visits was 11. Significant mean changes in clinical laboratory risk factors over the duration of care were: À0.65% for HbA1c ( p ¼ 0.046), À45 mg=dL for TAG ( p ¼ 0.037), À7 mm Hg in SBP ( p ¼ 0.02), and À5 mm Hg in DBP ( p ¼ 0.003). Mean changes for cholesterol did not reach statistical significance. The percentage of patients who reached new control, had clinically significant risk factor improvements, or had any improvement was: 26%, 42%, and 68% for HbA1c, 7%, 28%, and 62% for LDL, 0%, 25%, and 39% for HDL, 14%, 38%, and 52% for TAG, 16%, 51%, and 86% for SBP, and 27%, 54%, and 70% for DBP. Comments/conclusions: These preliminary outcomes suggest that risk factor improvements occur during naturopathic care for diabetes, although the contribution of naturopathic care to these changes cannot be determined. Effectiveness and generalizability of naturopathic approaches in treating type 2 diabetes should be evaluated in controlled prospective studies in representative populations or randomized trials.

The Journal of Alternative and Complementary Medicine, 2007

To develop a model to direct the prescription of nutritional and botanical medicines in the treat... more To develop a model to direct the prescription of nutritional and botanical medicines in the treatment of type 2 diabetes for both clinical and research purposes. Available literature on nutritional and botanical medicines was reviewed and categorized as follows: antioxidant/anti-inflammatory; insulin sensitizer; and beta-cell protectant/insulin secretagogue. Literature describing laboratory assessment for glycemic control, insulin resistance, and beta-cell reserve was also reviewed and a clinical decision tree was developed. Clinical algorithms were created to guide the use of nutritional and botanic medicines using validated laboratory measures of glycemic control, insulin sensitivity, and beta-cell reserve. Nutrient and botanic medicines with clinical trial research support include coenzyme Q10, carnitine, alpha-lipoic acid, N-acetylcysteine, vitamin D, vitamin C, vitamin E, chromium, vanadium, omega-3 fatty acids, cinnamon (Cinnamomum cassia), fenugreek (Trigonella foenum-graecum), and gymnema (Gymnema sylvestre). Clinical algorithms can direct supplementation in clinical practice and provide research models for clinical investigation. Algorithms also provide a framework for integration of future evidence as it becomes available. Research funding to investigate potentially beneficial practices in complementary medicine is critically important for optimal patient care and safety.

Journal of Nutrigenetics and Nutrigenomics, 2015

Observational research associating 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms... more Observational research associating 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms with risk of autism, depression, cancer, and cardiovascular disease has led to increased diagnoses of MTHFR; however, doctors lack knowledge about safety, effectiveness, and clinical implications of MTHFR treatment. Treatment strategies are hypothetical and mechanistically based, including methylfolate with or without other B vitamins. This study was designed to formally describe patient and health care provider experiences with the diagnosis and clinical management of MTHFR. Guided by a structured interview guide, a qualitative study queried patients' and providers' observations regarding: testing indications, reaction to results, treatment protocols, and clinical response including adverse effects. Thirty patients and 8 doctors participated. Patient themes included emotionality associated with diagnosis, classification of signs and symptoms, and challenges with treatment. They expressed confusion over their diagnosis, and frustration with the state of knowledge their providers had regarding MTHFR. Testing indications included: fatigue (21%), hormone imbalances (13%), and neurological symptoms (13%) including brain fog (8%). Patients reported improvements in physical (60%) and mental/behavioral symptoms (36%) following treatment. A minority of participants reported side effects, but they occurred in almost every body system and ranged in severity. Doctors relied on trial and error to determine treatment doses, frequency and components. MTHFR testing results in variable clinical processes in domains related to delivery of diagnosis and prognosis, and therapeutic options. However, patients report largely positive experiences. Clinicians and patients would benefit from therapeutic algorithms based on rigorous research.

Integrative medicine

Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are the well-established s... more Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are the well-established standards by which clinicians identify individuals at risk for coronary artery disease (CAD), yet nearly 50% of people who have a myocardial infarction have normal cholesterol levels. Measurement of additional biomarkers may be useful to more fully stratify patients according to disease risk. The typical lipid panel includes TC, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs). Emerging biomarkers for cardiovascular risk include measures of LDL-C pattern, size, and density; LDL particle number; lipoprotein(a); apolipoproteins (apoA1 and apoB100 being the most useful); C-reactive protein; and lipoprotein-associated phospholipase A(2). Some of these emerging biomarkers have been proven to add to, or be more accurate than, traditional risk factors in predicting coronary artery disease and, thus, may be useful for clinical decision-making in high-risk patients and ...

Objectives: We seek to represent the general landscape and outcomes of clinical studies of naturo... more Objectives: We seek to represent the general landscape and outcomes of clinical studies of naturopathic practice, with research intervention models consistent with naturopathic whole practice (rather than single therapeutic modalities) including observational studies in licensed No. American naturopathic medicine to generate hypotheses for further study and to identify gaps in knowledge. Conclusions: Formal whole practice studies in naturopathic medicine are a recent phenomenon in No. America. All studies meeting criteria showed signals of benefit, sometimes quite strong, but also have methodological weaknesses. The review provides evidence of effectiveness and cost savings in chronic diseases in the observed or validity-modeled practice of trained and licensed naturopathic doctors.

Reproductive Biology and Endocrinology, 2015

The placenta is an essential organ that provides nutrients and oxygen to the developing fetus and... more The placenta is an essential organ that provides nutrients and oxygen to the developing fetus and removes toxic waste products from the fetal circulation. Maintaining placental blood osmotic pressure and blood flow is crucial for viable offspring. The renin-angiotensin system (RAS) in the placenta is a key player in the regulation of maternal-fetal blood flow during pregnancy. Therefore, the aim of this study was to determine if RAS genes are differentially expressed in mid to late gestation in rat placenta. Whole placental tissue samples from pregnant Sprague Dawley rats at embryonic (E) days 14.25, 15.25, 17.25 and 20 (n = 6 for each gestational age) were used for genome-wide gene expression by microarray. RAS genes with expression differences of >2 fold were further analyzed. Quantitative Real-Time PCR (qPCR) was performed on independent samples to confirm and validate microarray data. Immunohistochemisty and Western blotting were performed on a differentially expressed novel RAS pathway gene (ANPEP). Six out of 17 genes of the RAS pathway were differentially expressed at different gestational ages. Gene expression of four genes (Angiotensin converting enzyme (Ace), angiotensin converting enzyme 2 (Ace2), membrane metalloendopeptidase (Mme) and angiotensin II receptor 1A (Agtr1a)) were significantly upregulated at E20 whereas two others (Thimet oligopeptidase 1 (Thop1) and Alanyl aminopeptidase (Anpep)) were downregulated at E20 prior to the onset of labour. These changes were confirmed by qPCR. Western blots revealed no overall differences in ANPEP protein expression in the placentae. Immunohistochemical studies, however, indicated that the localization of ANPEP differed at E17.25 and E20 as ANPEP localization in the giant trophoblast cell of the junctional zone was no longer detectable at E20. The current study investigated the expression of members of the RAS pathway in rat placentae and observed significantly altered expression of 6 RAS genes at 4 gestational ages. These findings present the need for further comprehensive investigation of RAS genes in normal and complicated pregnancies.

Integrative Medicine Research, 2015

Mediators of Inflammation, 2015

Mammalian placentation is a vital facet of the development of a healthy and viable offspring. Thr... more Mammalian placentation is a vital facet of the development of a healthy and viable offspring. Throughout gestation the placenta changes to accommodate, provide for, and meet the demands of a growing fetus. Gestational gene expression is a crucial part of placenta development. The endocannabinoid pathway is activated in the placenta and decidual tissues throughout pregnancy and aberrant endocannabinoid signaling during the period of placental development has been associated with pregnancy disorders. In this study, the gene expression of eight endocannabinoid system enzymes was investigated throughout gestation. Rat placentae were obtained at E14.25, E15.25, E17.25, and E20, RNA was extracted, and microarray was performed. Gene expression of enzymes Faah, Mgll, Plcd4, Pld1, Nat1, Daglα, and Ptgs2 was studied (cohort 1, microarray). Biological replication of the results was performed by qPCR (cohort 2). Four genes showed differential expression (Mgll, Plcd4, Ptgs2, and Pld1), from mid to late gestation. Genes positively associated with gestational age were Ptgs2, Mgll, and Pld1, while Plcd4 was downregulated. This is the first comprehensive study that has investigated endocannabinoid pathway gene expression during rat pregnancy. This study provides the framework for future studies that investigate the role of endocannabinoid system during pregnancy.

Food Chemistry, 2015

A novel paper-based Nanoceria Reducing Antioxidant Capacity (NanoCerac) assay for antioxidant det... more A novel paper-based Nanoceria Reducing Antioxidant Capacity (NanoCerac) assay for antioxidant detection (Sharpe, Frasco, Andreescu, & Andreescu, 2012), has been adapted for the first time as a high-throughput method, in order to measure the effect of brewing conditions and re-infusion on the antioxidant capacity of twenty-four commercial green teas. The oxygen radical absorbance capacity (ORAC) assay, frequently applied to complex foods and beverages, was used as a comparator measure of antioxidant capacity. A novel measure of sustained antioxidant capacity, the total inherent antioxidant capacity (TI-NanoCerac and TI-ORAC) was measured by infusing each tea six times. Effects of brewing conditions (temperature, brew time, etc.) were assessed using one popular tea as a standard. Both NanoCerac and ORAC assays correlated moderately (R(2) 0.80±0.19). The average first-brew NanoCerac, TI-NanoCerac, first-brew ORAC and TI-ORAC were: 0.73±0.1GAE/g tea; 2.4±0.70mmolGAE/g tea; 1.0±0.3mmolTE/g tea and 2.1±0.71mmolTE/g tea respectively. Brewing conditions including water temperature and infusion time significantly affected antioxidant capacity. The high-throughput adaptation of the original NanoCerac assay tested here offered advantages over ORAC, including portability and rapid analysis.

Nutrients, 2015

The leading causes of mortality and morbidity worldwide are cardiovascular disease (high blood pr... more The leading causes of mortality and morbidity worldwide are cardiovascular disease (high blood pressure, high cholesterol and renal disease), cancer and diabetes. It is increasingly obvious that the development of these diseases encompasses complex interactions between adult lifestyle and genetic predisposition. Maternal malnutrition can influence the fetal and early life environment and pose a risk factor for the future development of adult diseases, most likely due to impaired organogenesis in the developing offspring. This then predisposes these offspring to cardiovascular disease and renal dysfunction in adulthood. Studies in experimental animals have further illustrated the significant impact maternal diet has on offspring health. Many studies report changes in kidney structure (a reduction in the number of nephrons in the kidney) in offspring of protein-deprived dams. Although the early studies suggested that increased blood pressure was also present in offspring of protein-re...

Global Advances in Health and Medicine, 2013

Interest in case studies has undergone a resurgence concurrent with increasing prioritization of ... more Interest in case studies has undergone a resurgence concurrent with increasing prioritization of illustrations of patient-centered care. However, substantial inclusion of the patient in these reports remains limited. Here, a doctor and patient collaborate to present her case report of self-directed mindfulness training and the subsequent changes in blood pressure, migraine frequency, and quality of life. After receiving encouragement from her naturopathic doctor, the patient initiated an 8-week program in mindfulness training following the Kabat-Zinn protocol and logged her daily blood pressure and symptoms before and after meditation sessions over an 11-week period. Patient-reported outcomes included decreased perceived stress, increased focus, and a newfound sense of centeredness and calm. Changes in objective outcomes were clinically and statistically significant, including reductions in mean systolic and diastolic blood pressure between week 1 and week 11 (P = .0001 and P = .0004 for systolic and diastolic, respectively, by paired, 2-sided t-tests). Self-reported frequency of chronic migraine was also reduced. Critical to the patient's success was that mindfulness training was first approached in a simple, accessible manner prior to embarking on a deeper, extended experience. Self-directed mindfulness training can have a meaningful impact on both subjective and objective health outcomes. It may take years of encouragement from a healthcare provider before a patient is ready to adopt a mind-body practice; it is important to recognize and counsel patients with messages appropriate to their stage of change and self-efficacy. Additionally, case studies that combine the voice of the clinician and the patient can provide useful illustrations of truly patient-centered care.

Biodemography and Social Biology, 2014

The purpose of this study was to examine biological and behavioral explanations for gender differ... more The purpose of this study was to examine biological and behavioral explanations for gender differences in leukocyte telomere length (LTL), a biomarker of cell aging that has been hypothesized to contribute to women's greater longevity. Data are from a subsample (n = 851) of the Multi-Ethnic Study of Atherosclerosis, a population-based study of women and men aged 45 to 84. Mediation models were used to examine study hypotheses. We found that women had longer LTL than men, but the gender difference was smaller at older ages. Gender differences in smoking and processed meat consumption partially mediated gender differences in telomere length, whereas gender differences in estradiol, total testosterone, oxidative stress, and body mass index did not. Neither behavioral nor biological factors explained why the gender difference in LTL was smaller at older ages. Longitudinal studies are needed to assess gender differences in the rate of change in LTL over time; to identify the biological, behavioral, and psychosocial factors that contribute to these differences throughout the life course; and to determine whether gender differences in LTL explain the gender gap in longevity.

The placenta plays a central role in determining the outcome of pregnancy. It undergoes changes d... more The placenta plays a central role in determining the outcome of pregnancy. It undergoes changes during gestation as the fetus develops and as demands for energy substrate transfer and gas exchange increase. The molecular mechanisms that coordinate these changes have yet to be fully elucidated. The study performed a large scale screen of the transcriptome of the rat placenta throughout mid-late gestation (E14.25-E20) with emphasis on characterizing gestational age associated changes in the expression of genes invoved in angiogenic pathways. Sprague Dawley dams were sacrificed at E14.25, E15.25, E17.25 and E20 (n = 6 per group) and RNA was isolated from one placenta per dam. Changes in placental gene expression were identifed using Illumina Rat Ref-12 Expression BeadChip Microarrays. Differentially expressed genes (.2fold change, ,1% false discovery rate, FDR) were functionally categorised by gene ontology pathway analysis. A subset of differentially expressed genes identified by microarrays were confirmed using Real-Time qPCR. The expression of thirty one genes involved in the angiogenic pathway was shown to change over time, using microarray analysis (22 genes displayed increased and 9 gene decreased expression). Five genes (4 up regulated: Cd36, Mmp14, Rhob and Angpt4 and 1 down regulated: Foxm1) involved in angiogenesis and blood vessel morphogenesis were subjected to further validation. qPCR confirmed late gestational increased expression of Cd36, Mmp14, Rhob and Angpt4 and a decrease in expression of Foxm1 before labour onset (P,0.0001). The observed acute, pre-labour changes in the expression of the 31 genes during gestation warrant further investigation to elucidate their role in pregnancy.

Journal of nutritional science, 2013

The high fat content in Western diets probably affects placental function during pregnancy with p... more The high fat content in Western diets probably affects placental function during pregnancy with potential consequences for the offspring in the short and long term. The aim of the present study was to compare genome-wide placental gene expression between rat dams fed a high-fat diet (HFD) and those fed a control diet for 3 weeks before conception and during gestation. Gene expression was measured by microarray and pathway analysis was performed. Gene expression differences were replicated by real-time PCR and protein expression was assessed by Western blot analysis. Placental and fetal weights at E17.25 were not altered by exposure to the maternal HFD. Gene pathways targeting placental growth, blood supply and chemokine signalling were up-regulated in the placentae of dams fed the HFD. The up-regulation in messenger RNA expression for five genes Ptgs2 (fatty acid cyclo-oxidase 2; COX2), Limk1 (LIM domain kinase 1), Pla2g2a (phospholipase A2), Itga1 (integrin α-1) and Serpine1 was co...

The International Journal of Biochemistry & Cell Biology, 2012

Adipocyte Obesity Adipose tissue metabolism Obesity related hypertension Developmental programmin... more Adipocyte Obesity Adipose tissue metabolism Obesity related hypertension Developmental programming of health and disease a b s t r a c t Globally 30% of adults are overweight or obese. The white adipocyte is a major component of adipose tissue, and as the obesity epidemic increases it is critically important to understand the factors determining adipocyte development and function. Adipogenesis has two distinct phases; determination of the adipocyte from a multipotent stem cell, and terminal differentiation of a pre-adipocyte into a mature adipocyte. The environment encountered in early life can alter adipocyte number and size and potentially impact upon adipocyte endocrine function in adulthood. These alterations may contribute to the pathophysiology of chronic diseases and thus targeted therapy of the adipocyte has great potential for treating the current obesity epidemic.

PLoS ONE, 2012

Differences in the effectiveness of diverse healthcare providers to promote health behavior chang... more Differences in the effectiveness of diverse healthcare providers to promote health behavior change and successful diabetes self-care have received little attention. Because training in naturopathic medicine (NM) emphasizes a patient-centered approach, health promotion, and routine use of clinical counseling on wellness and prevention, naturopathic physicians (NDs) may be particularly well-prepared for promoting behavior change. However, patients' experiences with NM have not been well studied. This study provides the first report of the perceptions of persons with type 2 diabetes of their first experiences with naturopathic care for their diabetes. Following their participation in a one-year prospective cohort study of adjunctive naturopathic care for diabetes, twenty-two patients were interviewed about their experiences working with a naturopathic physician. Using a content analysis approach, nine dominant themes were identified. Three themes characterized the nature of the ND-patient interaction: 1) patient-centered, 2) holistic health rather than diabetes focused, and 3) collaborative. Five themes characterized the content of the clinical encounter: 1) individualized and detailed health promotion, 2) counseling that promoted self-efficacy, 3) pragmatic and practical self-care recommendations, 4) novel treatment options that fostered hopefulness, and 5) patient education that addressed both diabetes self-care and general health. A ninth theme was cross-cutting: the contrast between ND care and conventional medical care. Results indicate that the routine clinical approach used by NDs is consistent with behavior change theory and clinical strategies found most effective in promoting self-efficacy and improving clinical outcomes.

Medical Anthropology Quarterly, 2012

Building on a dialogue between three trained naturopaths and a proponent of critical medical anth... more Building on a dialogue between three trained naturopaths and a proponent of critical medical anthropology (CMA), this article highlights the relationship between health and society from the viewpoint of two fields that share this focal concern. Both naturopathy and CMA are committed to the notion of holistic health, although their approaches have historically been somewhat different. The responses of the three naturopaths to CMA exhibit both similarities and differences, particularly in terms of insights that CMA may make to naturopathy. This essay also articulates the CMA perspective of naturopathy and posits lessons that naturopathy can teach CMA.

Journal of Hypertension, 2012

ABSTRACT Background: Maternal obesity may programme the development of hypertension and renal dis... more ABSTRACT Background: Maternal obesity may programme the development of hypertension and renal disease in offspring. It is not known whether high saturated fat intake in pregnancy in the absence of maternal obesity is deleterious to offspring cardiovascular health. Aims: To determine whether excessive maternal fat intake in pregnancy and suckling programmes renal and cardiovascular disease in adult offspring. Methods: Female Sprague-Dawley rats (n = 5-8) were fed a control (C) or high saturated-fat (HF) diet for 3 weeks before mating, during pregnancy and lactation. From weaning, offspring were chow fed ad libitum. At 6 and 12 months of age glomerular filtration rate (GFR) and effective renal blood flow (eRBF) were estimated in anaesthetized rats by [3H]-inulin and [14C]-para-aminohippurate clearance. Mean arterial pressure (MAP) and heart rate were determined by radiotelemetry. Data were analysed by two-way ANOVA. Results: Maternal fat intake did not significantly alter offspring renal or cardiovascular function at 6 months. MAP was significantly elevated in 1 year-old HF offspring (OHF male; 98.8 +/- 3.6, female 101.9 +/- 3.3 compared with controls (OC male; 90.7 +/- 2.7 mmHg, female 90.1 +/- 3.3 mmHg, P<0.05). There was no significant effect of maternal diet on GFR or sodium reabsorption but OHF males had greater eRBF (4.95 +/- 0.44 ml/min/gkw) than OC (2.88 +/- 0.67 ml/min/gkw, P<0.05). eRBF in OHF females (4.6 +/- 1.5 ml/min/gkw) was significantly less than OC (7.7 +/- 1.9 ml/min/gkw, P<0.05). Conclusions: Maternal diets high in saturated fat can programme hypertension and sexually dimorphic alterations in renal haemodynamics in offspring.

The Journal of Clinical Endocrinology & Metabolism, 2014

As a result of research suggesting increased health risk with low serum 25-hydroxycholecalciferol... more As a result of research suggesting increased health risk with low serum 25-hydroxycholecalciferol (25(OH)D), health care providers are measuring it frequently. Providers and patients are faced with treatment choices when low status is identified. To compare the safety and efficacy of three vitamin D3 dietary supplements with different delivery matrices. A 12-week, parallel group, single-masked, clinical trial was conducted in Seattle, Washington and Kailua Kona, Hawaii. Sixty-six healthy adults with (25(OH)D) <33 ng/mL were randomly assigned to take one of three D3 supplements, ie, a chewable tablet (TAB), an oil-emulsified drop (DROP), or an encapsulated powder (CAP) at a label-claimed dose of 10,000 IU/day. Actual D3 content was assessed by a third party and the results adjusted based on the actual D3 content administered. Mean change in 25(OH)D/mcg D3 administered; difference in the proportion of D3 insufficient participants (ie, 25(OH)D ≤30 ng/mL) reaching sufficiency (ie, 25(OH)D ≥30 ng/mL); and mean change in serum 1, 25-dihydroxycholecalciferol were measured. In two of the three products tested, the measured vitamin D3 content varied considerably from the label-claimed dose. Differences in 25(OH)D/mcg D3 administered were significantly different between groups (P = .04; n = 55). Pairwise comparisons demonstrated DROP resulted in a greater increase than TAB (P < .05) but not than CAP. TAB was not different from CAP. The proportions reaching sufficiency were: 100% (TAB and CAP) and 80% (DROP) (P = .03 between groups; n = 55). 1, 25-Dihydroxycholecalciferol did not change significantly in any group. Oil-emulsified vitamin D3 supplements resulted in a greater mean change in serum 25(OH)D concentration, but fewer patients reaching vitamin D sufficiency, than chewable or encapsulated supplements.

The Journal of Alternative and Complementary Medicine, 2014

The Journal of Alternative and Complementary Medicine, 2009

Background: Survey findings report that 48% of people with type 2 diabetes use complementary and ... more Background: Survey findings report that 48% of people with type 2 diabetes use complementary and alternative medicine (CAM) practice. Publications suggest a high incidence of health promotion counseling in naturopathic practice, yet clinical data on risk factor changes are not available in the literature. Objectives: The primary aim of this study was to describe clinical risk factor changes during the utilization of naturopathic CAM services in patients with type 2 diabetes. Design: A retrospective, observational study design was used to describe naturopathic care. Setting: Abstracted medical charts were from patients of the Bastyr Center for Natural Health in Seattle, WA. Participants: The patients in this study had type 2 diabetes and received naturopathic care between 2001 and 2006. Outcomes: Abstracted data included patient demographics, duration of care, number of visits, laboratory values for hemoglobin A1c (HbA1c), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol, triglycerides (TAG); and systolic=diastolic blood pressure (SPB, DBP). Results: Thirty-seven (37) patient records met inclusion criteria and were abstracted in detail. Mean and median duration of care were 27 and 20 months, respectively. The mean number of visits was 11. Significant mean changes in clinical laboratory risk factors over the duration of care were: À0.65% for HbA1c ( p ¼ 0.046), À45 mg=dL for TAG ( p ¼ 0.037), À7 mm Hg in SBP ( p ¼ 0.02), and À5 mm Hg in DBP ( p ¼ 0.003). Mean changes for cholesterol did not reach statistical significance. The percentage of patients who reached new control, had clinically significant risk factor improvements, or had any improvement was: 26%, 42%, and 68% for HbA1c, 7%, 28%, and 62% for LDL, 0%, 25%, and 39% for HDL, 14%, 38%, and 52% for TAG, 16%, 51%, and 86% for SBP, and 27%, 54%, and 70% for DBP. Comments/conclusions: These preliminary outcomes suggest that risk factor improvements occur during naturopathic care for diabetes, although the contribution of naturopathic care to these changes cannot be determined. Effectiveness and generalizability of naturopathic approaches in treating type 2 diabetes should be evaluated in controlled prospective studies in representative populations or randomized trials.

The Journal of Alternative and Complementary Medicine, 2007

To develop a model to direct the prescription of nutritional and botanical medicines in the treat... more To develop a model to direct the prescription of nutritional and botanical medicines in the treatment of type 2 diabetes for both clinical and research purposes. Available literature on nutritional and botanical medicines was reviewed and categorized as follows: antioxidant/anti-inflammatory; insulin sensitizer; and beta-cell protectant/insulin secretagogue. Literature describing laboratory assessment for glycemic control, insulin resistance, and beta-cell reserve was also reviewed and a clinical decision tree was developed. Clinical algorithms were created to guide the use of nutritional and botanic medicines using validated laboratory measures of glycemic control, insulin sensitivity, and beta-cell reserve. Nutrient and botanic medicines with clinical trial research support include coenzyme Q10, carnitine, alpha-lipoic acid, N-acetylcysteine, vitamin D, vitamin C, vitamin E, chromium, vanadium, omega-3 fatty acids, cinnamon (Cinnamomum cassia), fenugreek (Trigonella foenum-graecum), and gymnema (Gymnema sylvestre). Clinical algorithms can direct supplementation in clinical practice and provide research models for clinical investigation. Algorithms also provide a framework for integration of future evidence as it becomes available. Research funding to investigate potentially beneficial practices in complementary medicine is critically important for optimal patient care and safety.