William S Harris

William S Harris
University of South Dakota | USD · Department of Internal Medicine

About

548
Publications
57,906
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40,298
Citations
Citations since 2016
164 Research Items
13995 Citations
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201620172018201920202021202205001,0001,5002,000
201620172018201920202021202205001,0001,5002,000
Introduction
Skills and Expertise

Publications

Publications (548)
Article
Full-text available
There is inconsistency regarding the association between long-chain n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA; 20:5n3) and docosahexaenoic acid (DHA; 22:6n3) and the risk of type 2 diabetes. The present study aimed to investigate the association between the Omega-3 Index (erythrocyte EPA + DHA) and glycemic status as a func...
Article
Full-text available
Information on the Omega-3 Index (O3I) in the United Kingdom (UK) are scarce. The UK-Biobank (UKBB) contains data on total plasma omega-3 polyunsaturated fatty acids (n3-PUFA%) and DHA% measured by NMR. The aim of our study was to create an equation to estimate the O3I (eO3I) from these data. We first performed an interlaboratory experiment with 25...
Article
Background and Objectives Diet may be a key contributor to brain health in midlife. In particular, Omega-3 fatty acids have been related to better neurological outcomes in older adults. However, studies focusing on midlife are lacking. We investigated the cross-sectional association of red blood cell (RBC) Omega-3 fatty acid concentrations with MRI...
Preprint
Full-text available
Background The role of nutritional status and risk for contracting and/or suffering adverse outcomes from COVID-19 infection are unclear. Preliminary studies suggest that higher n-3 PUFA intakes may be protective. Objectives: The purpose of this study was to compare risk for three COVID-19 outcomes (testing positive, hospitalization, and death) as...
Preprint
Information on the Omega-3 Index (O3I) in the United Kingdom (UK) are scarce. The UK-Biobank (UKBB) contains data on total plasma omega-3 polyunsaturated fatty acids (n3-PUFA%) and DHA% measured by NMR. The aim of our study was to create an equation to estimate the O3I (eO3I) from these data. We first performed an interlaboratory experiment with 25...
Article
Full-text available
Docosahexaenoic acid (DHA) might help prevent Alzheimer’s disease (AD). Red blood cell (RBC) status of DHA is an objective measure of long-term dietary DHA intake. In this prospective observational study conducted within the Framingham Offspring Cohort (1490 dementia-free participants aged ≥65 years old), we examined the association of RBC DHA with...
Article
Higher omega-3 fatty acid blood levels, as assessed by the Omega-3 Index (O3I, erythrocyte EPA+DHA percentage), have been linked with lower risk for cardiovascular disease and total mortality. Since seafood is an excellent source of EPA and DHA, we reasoned that people living on the coast with direct access to fresh seafood might have higher O3I le...
Article
Full-text available
Primary ventricular fibrillation (PVF) is a major driver of cardiac arrest in the acute phase of ST-segment elevation myocardial infarction (STEMI). Enrichment of cardiomyocyte plasma membranes with dietary polyunsaturated fatty acids (PUFA) reduces vulnerability to PVF experimentally, but clinical data are scarce. PUFA status in serum phospholipid...
Article
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Background: n-3 and n-6 PUFAs have physiologic roles in sleep processes, but little is known regarding circulating n-3 and n-6 PUFA and sleep parameters. Objectives: We sought to assess associations between biomarkers of n-3 and n-6 PUFA intake with self-reported sleep duration and difficulty falling sleeping in the Fatty Acids and Outcome Resea...
Article
Recent trials in pregnant women on the effects of supplemental DHA on early preterm birth (ePTB) risk have shown that there is a maternal blood docosahexaenoic acid (DHA) level below which risk for ePTB was increased and supplemental DHA was effective at reducing risk. However, DHA levels were expressed in different terms across these trials making...
Article
Red blood cell (RBC) fatty acid (FA) patterns are becoming recognized as long-term biomarkers of tissue FA composition, but different analytical methods have complicated inter-study and international comparisons. Here we report RBC FA data, with a focus on the Omega-3 Index (EPA + DHA in % of total FAs in RBC), from samples of seven countries (USA,...
Article
Full-text available
Background: Evidence for the role of omega-3 fatty acids in the prevention of atrial fibrillation (AF) remain inconsistent, with some recent RCTs even suggesting possible harm. Whether long-term dietary intake of these fatty acids, as assessed using objective biomarkers, is related to AF is not known. Aims: To prospectively evaluate circulating and...
Article
OBJECTIVE Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis. RESEARCH DESIGN AND METHODS We included data from an in...
Article
The neutrophil-lymphocyte ratio (NLR) is a biomarker of systemic inflammation and measures innate-adaptive immune system balance. The omega-3-index (O3I) measures the amount of EPA+DHA in blood. Both a low O3I and an elevated NLR are associated with increased risk for chronic disease and mortality, including cardiovascular diseases and cancer. Hypo...
Presentation
Full-text available
RBC long-chain omega-3 (n–3) fatty acid (FA) percentages (of total fatty acids) are associated with lower risk for total mortality, but it is unknown if a suite of FAs could improve risk prediction. Our objective was to compare a combination of RBC FA levels with standard risk factors for cardiovascular disease (CVD) in predicting risk of all-cause...
Article
Low red blood cell (RBC) membrane content of EPA and DHA, i.e., the omega-3 index (O3I), and elevated RBC distribution width (RDW) are risk factors for all-cause mortality. O3I and RDW are related with membrane fluidity and deformability. Our objective was to determine if there is a relationship between O3I and RDW in healthy adults. Subjects witho...
Preprint
Full-text available
Low red blood cell (RBC) membrane content of EPA and DHA, i.e., the omega-3 index (O3I), and elevated RBC distribution width (RDW) are risk factors for all-cause mortality. O3I and RDW are related with membrane fluidity and deformability. Our objective was to determine if there is a relationship between O3I and RDW in healthy adults. Subjects witho...
Preprint
Full-text available
The EPA+DHA content of red blood cell membranes, i.e., the omega-3 index (O3I), reflects omega-3 fatty acid status. EPA and DHA modulate inflammation via effects on cell signaling and the synthesis of pro-resolving lipid mediators. The neutrophil-lymphocyte ratio (NLR) is a measure of innate-adaptive immune system balance and is a biomarker of syst...
Article
Full-text available
Background RBC long-chain omega-3 (n–3) fatty acid (FA) percentages (of total fatty acids) are associated with lower risk for total mortality, but it is unknown if a suite of FAs could improve risk prediction. Objectives The objective of this study was to compare a combination of RBC FA levels with standard risk factors for cardiovascular disease...
Article
Background The roles of omega-3 (n3) fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and low-dose aspirin in the primary prevention of ischemic cardiovascular disease (CVD) are controversial. Since omega-3 (n3) fatty acids and aspirin affect cyclooxygenase activity in platelets, there could be a clinically-relevant effect o...
Article
Full-text available
The health effects of omega-3 fatty acids have been controversial. Here we report the results of a de novo pooled analysis conducted with data from 17 prospective cohort studies examining the associations between blood omega-3 fatty acid levels and risk for all-cause mortality. Over a median of 16 years of follow-up, 15,720 deaths occurred among 42...
Article
Full-text available
Background The factors other than dietary intake that determine tissue concentrations of EPA and DHA remain obscure. Prior studies suggested that, in women, endogenous estrogen may accelerate synthesis of DHA from ɑ-linolenic acid (ALA), but the effects of exogenous estrogen on RBC n–3 (ɷ-3) PUFA concentrations are unknown. Objective We tested the...
Article
Full-text available
OBJECTIVE Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of a-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an in...
Article
Full-text available
Objective: Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an...
Article
Full-text available
Background: The association between long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) and prostate cancer (PC) remains unclear. Methods: We compared incident PC rates as a function of the Omega-3 Index [O3I, erythrocyte eicosapentaenoic and docosahexaenoic acids (EPA + DHA)] in 5607 men (40-80 years of age) seen at the Cooper Clinic who...
Article
Very-long chain omega-3 fatty acids (EPA and DHA) have anti-inflammatory properties that may help reduce morbidity and mortality from COVID-19 infection. We conducted a pilot study in 100 patients to test the hypothesis that RBC EPA+DHA levels (the Omega-3 Index, O3I) would be inversely associated with risk for death by analyzing the O3I in banked...
Article
Background The importance of providing the newborn with docosahexaenoic acid (DHA) from breast milk is well established. However, women in the United States, on average, have breast milk DHA levels of 0.20%, which is below the worldwide average (and proposed target) of >0.32%. Additionally, the relationship between maternal red blood cell (RBC) and...
Preprint
Full-text available
Very-long chain omega-3 fatty acids (EPA and DHA) have anti-inflammatory properties that may help reduce morbidity and mortality from COVID-19 infection. We conducted a pilot study in 100 patients to test the hypothesis that RBC EPA+DHA levels (the Omega-3 Index, O3I) would be inversely associated with risk for death by analyzing the O3I in banked...
Article
Background and Purpose The red blood cell fatty acid composition objectively reflects the long-term dietary intake of several fatty acids. In patients undergoing carotid endarterectomy, we explored whether red blood cell status of selected fatty acids related to symptomatic carotid artery disease. Methods We included patients with symptomatic (n=2...
Article
Background Previous studies have suggested that omega-3 polyunsaturated fatty acids (n-3 PUFA) can favorably influence cardiac autonomic tone. However, data regarding n-3 PUFA status and heart rate recovery (HRR) in healthy adults are sparse. Purpose To examine the association between n-3 PUFA status and HRR. Methods Participants included 13,912...
Article
Background The effects of fish oil products containing docosahexaenoic acid (DHA) on LDL-C levels are controversial. Objective To determine if changes in erythrocyte DHA are associated with changes in LDL-C levels. Methods In this prospective observational study, erythrocyte DHA levels and LDL-C levels were measured in 9253 individuals who presen...
Article
Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, attenuates interstitial lung disease (ILD) in experimental models but human studies are lacking. We examined associations of circulating levels of DHA, and other polyunsaturated fatty acids, with hospitalization and death due to ILD over 12 years in the Multi-Ethnic Study of Atheros...
Article
Full-text available
Background De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D). Methods and findings Seventeen cohorts from 12 countries (...
Article
Objectives To assess associations between individual and total circulating n-3 fatty acids (FAs) with self-reported sleep duration and difficulty sleeping in the Fatty Acids and Outcome Research Consortium (FORCE). Methods De novo harmonized individual-level analyses were performed and pooled in 10 prospective studies (N = 22,717) with data on sle...
Article
Importance Aortic stenosis (AS) has no approved medical treatment. Identifying etiological pathways for AS could identify pharmacological targets. Objective To identify novel genetic loci and pathways associated with AS. Design, Setting, and Participants This genome-wide association study used a case-control design to evaluate 44 703 participants...
Article
Background: Several recent studies have linked higher blood levels of the long-chain omega-3 polyunsaturated fatty acids (PUFAs) with lower risk of certain disease outcomes, in particular cardiovascular disease (CVD). Limited studies have evaluated associations between n-3 PUFA levels and total and cause-specific mortality. Methods: We meta-analyze...
Article
In adipose, insulin functions to suppress intracellular lipolysis and secretion of non-esterified fatty acid (NEFA) into plasma. Current tests of insulin resistance do not test this response. We applied glucose and NEFA minimal models (MM) following a frequently sampled intravenous glucose tolerance test (FSIVGTT) to assess glucose-specific and NEF...
Article
Insulin resistance early after acute myocardial infarction is associated with increased heart failure and mortality. OMEGA-REMODEL was a prospective double-blind 1:1 randomized control trial of patients with AMI. We reported that 6-month treatment with omega-3 fatty acid (O-3FA) 4 g/day attenuated cardiac remodeling accompanied by reduction in infl...
Article
Ischemic heart disease (IHD) is a leading cause of mortality in the United States. There is substantial evidence that a sustained intake of industrially-produced trans fatty acids (IP-TFA) is associated with increased risk of fatal IHD. This has led many regulatory agencies to pressure dietary oil producers to remove IP-TFA from their products. Tha...
Article
Full-text available
Background The double-blind OMEGA-REMODEL placebo-controlled randomized trial of high-dose omega-3 fatty acids (O-3FA) post-acute myocardial infarction (AMI) reported improved cardiac remodeling and attenuation of non-infarct myocardial fibrosis. Fatty acid desaturase 2 (FADS2) gene cluster encodes key enzymes in the conversion of essential omega-3...
Conference Paper
Background Type 2 diabetes (T2D) is a major risk factor associated with cardiometabolic diseases, and a major contributor towards mortality and morbidity, given its rapidly rising prevalence worldwide. In experimental studies, trans-fatty acids (TFAs) exert harmful biologic effects that may affect T2D risk, but findings from observational studies r...
Article
Full-text available
Hypertriglyceridemia (triglycerides 200-499 mg/dL) is relatively common in the United States, whereas more severe triglyceride elevations (very high triglycerides, ≥500 mg/dL) are far less frequently observed. Both are becoming increasingly prevalent in the United States and elsewhere, likely driven in large part by growing rates of obesity and dia...
Article
Background: Supplemental long-chain omega-3 (n-3) fatty acids (EPA and DHA) raise erythrocyte EPA + DHA [omega-3 index (O3I)] concentrations, but the magnitude or variability of this effect is unclear. Objective: The purpose of this study was to model the effects of supplemental EPA + DHA on the O3I. Methods: Deidentified data from 1422 indivi...
Article
Background: The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) study demonstrated that 4 g/d of eicosapentaenoic acid (EPA) ethyl esters (icosapent ethyl [IPE]) reduced risk for major cardiovascular events by 25% in statin-treated patients with residual hypertriglyceridemia. How this treatment affected red b...
Article
Background: The Omega-3 Index (O3I; erythrocyte EPA+DHA as a percent of total fatty acids) is inversely related to risk for cardiovascular disease (CVD). The cardioprotective target O3I is 8%-12%. O3I levels in American regions with high CVD risk are poorly characterized. Purpose: To determine the O3I in individuals participating in a Seafood Nu...
Article
Three recent clinical trials have demonstrated the benefits of marine omega-3 fatty acids on cardiovascular disease end points. In the Vitamin D and Omega-3 Trial (VITAL), 840 mg/d of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) resulted in a 28% reduced risk for heart attacks, 50% reduced risk for fatal heart attacks, and 17% reduced...
Article
Objective: Studies of depressed psychiatric patients have suggested that antidepressant efficacy can be increased by adding eicosapentaenoic acid (EPA), one of the omega-3 fatty acids found in fish oils. The purpose of this study was to determine whether the addition of EPA improves the response to sertraline in depressed patients with or at high...
Article
Objectives: To assess prospective association between circulating biomarkers of individual trans fatty acids (TFAs) and incident type 2 diabetes (T2D) in diverse populations. Methods: A harmonized analysis of individual level data was conducted for TFA biomarkers and incident T2D by pooling ten prospective cohort or nested-case-control studies f...
Article
Objectives Both too little and too much sleep may be detrimental for health, and emerging evidence suggests links between diet and sleep duration. n-3 and n-6 fatty acids (FAs) have physiologic roles in sleep processes including initiation, regulation, and melatonin production. We aimed to assess the association of circulating n-3 and n-6 FA biomar...
Article
Background: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and ara...
Article
Full-text available
Background: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and ar...
Article
Full-text available
Studies show that the reduction in serum triglyceride concentrations with long-chain omega-3 fatty acid supplementation is highly variable among individuals. The objectives of this study were to compare the proportions of individuals whose triglyceride concentrations are lowered after high-dose docosahexaenoic (DHA) and eicosapentaenoic acid (EPA),...
Article
The purpose of this review is to consider the effects of the long-chain n -3 fatty acids found in marine foods, EPA and DHA, on risk for CVD, particularly fatal outcomes. It will examine both epidemiological and randomised controlled trial findings. The former studies usually examine associations between the dietary intake or the blood levels of EP...
Article
Background: An Omega-3 Index (O3I; EPA+DHA as a % of erythrocyte total fatty acids) in the desirable range (8%-12%) has been associated with improved heart and brain health. Objective: To determine the combination of fish intake and supplement use that is associated with an O3I of >8%. Design: Two cross-sectional studies comparing the O3I to E...
Article
Full-text available
Background and aims: It remains unclear how trans fatty acid (TFA) at low-level intake affect lipid levels and the development of acute coronary syndrome (ACS). The study aimed to investigate how plasma TFA composition differs between male patients with ACS and healthy men. Methods: Plasma fatty acid (FA) composition (as determined by gas chroma...
Article
Population‐based data suggest that individuals who consume large dietary amounts of n‐3 polyunsaturated fatty acids (PUFA) have lower odds of peripheral artery disease (PAD); however, clinical studies examining n‐3 PUFA levels in patients with PAD are sparse. The objective of this study is to compare erythrocyte membrane fatty acid (FA) content bet...
Article
Full-text available
Context: The essential omega-3 fatty acids (ω-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exhibit vital biological roles and are critical for cardiovascular and neurologic health. Compared with the general population, football athletes may be at an increased risk of cardiovascular disease. Further, those same athletes are als...
Article
Full-text available
Background: The prognostic value of erythrocyte levels of n-6 fatty acids (FAs) for total mortality and cardiovascular disease (CVD) outcomes remains an open question. Methods: We examined cardiovascular (CV) outcomes and death in 2500 individuals in the Framingham Heart Study Offspring cohort without prevalent CVD (mean age 66 years, 57% women) as...
Preprint
Full-text available
Background: The prognostic value of erythrocyte levels of the n-6 fatty acids (FAs) for total mortality and cardiovascular disease (CVD) outcomes remains an open question. Methods: We examined CV outcomes and death in 2500 individuals in the Framingham Heart Study Offspring cohort without prevalent CVD (mean age 66 years, 57% women) as a function o...
Article
Full-text available
Background Fish oil is among the most common natural supplements for treatment of hypertriglyceridemia or prevention of cardiovascular disease. However, concerns about theoretical bleeding risk have led to recommendations that patients should stop taking fish oil before surgery or delay in elective procedures for patients taking fish oil by some he...
Article
Full-text available
Background: We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D). Methods and findings: Sixteen prospective cohorts from 12 countries (7 from the United States, 7...