Effects of Vitamin D and Marine Omega-3 Fatty Acids on Anemia

Effects of Vitamin D and Marine Omega-3 Fatty Acids on Anemia in the Elderly

The VITamin D and OmegaA-3 TriaL (VITAL; NCT01169259) is a randomized clinical trial in 20,000 U.S. men and women studying whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk of developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. This ancillary study is being conducted among VITAL participants and will study whether vitamin D or fish oil: (A) in the overall VITAL cohort, reduces the number of persons diagnosed with anemia and (B) in a subcohort of 900 participants seen in Boston, effects long-term changes of the proteins in blood in both anemic and non-anemic individuals who provide blood samples at the start of the study and again 2 years later.

Study Overview

• Status: Active, not recruiting
• Conditions: Anemia
• Intervention / Treatment: Dietary supplement: Fish oil placebo; Dietary supplement: Vitamin D3 placebo; Drug: omega-3 fatty acids (fish oil); Dietary supplement: Vitamin D3 .

Detailed Description

The VITamin D and OmegA-3 Trial (VITAL; NCT01169259) is a randomized clinical trial of vitamin D (in the form of D3 [cholecalciferol]) and marine omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements in the primary prevention of cancer and cardiovascular disease.

Eligible participants will be assigned by chance (like a coin toss) to one of four groups: (1) daily vitamin D3 and omega-3; (2) daily vitamin D3 and omega-3 placebo; (3) daily vitamin D and omega-3; or (4) daily vitamin D placebo and omega-3 placebo. Participants have an equal chance of being assigned to any of these four groups and a 3 out of 4 chance of getting at least one active agent.

Participants in all group will take two pills each day--one softgel that contains either vitamin D3 or vitamin D placebo and one capsule that contains either omega-3 or omega-3 placebo. Participants will receive their study pills in convenient calendar packages via U.S. mail.

Participants will also fill out a short (15-20 minute) questionnaire each year. The questionnaire asks about health; lifestyle habits such as physical exercise, diet, and smoking; use of medications and dietary supplements; family history of illness, and new medical diagnoses. Occasionally participants may receive a phone call from study staff to collect information or to clarify responses on the questions.

If a participant reports a new medical diagnosis of anemia on the short questionnaires, he or she will be invited to participate in this sub-study. If the participant consents, his or her medical record will be reviewed to confirm the diagnosis of anemia. We expect roughly 1,100 individuals to develop anemia while on the study.

Of the expected 20,000 participants in the VITAL trial, approximately 1,000 participants will be seen in Boston and given the opportunity to participate in optional research blood draws. This sub-study expects to receive approximately 10mL of the samples collected from 900 of these participants. This portion of blood will be used to evaluate the amount of different proteins in both anemic and non-anemic individuals. Blood samples will be collected at baseline and two years later.

• Study Type: Interventional
• Enrollment (Estimated): 2000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Participants in VITAL (NCT 01169259) who do not have anemia at baseline and who report a diagnosis of anemia on the VITAL follow-up questionnaires are eligible to participate in this ancillary study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Vitamin D + fish oil; Dietary Supplement: Vitamin D3 (cholecalciferol), 2000 IU per day. Other Name: cholecalciferol Drug: omega-3 fatty acids (fish oil) Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).	Drug: omega-3 fatty acids (fish oil); Dietary supplement: Vitamin D3 .
Active Comparator: Vitamin D + fish oil placebo; Dietary Supplement: Vitamin D3 (cholecalciferol), 2000 IU per day. Other Name: cholecalciferol Dietary Supplement: Fish oil placebo Fish oil placebo	Dietary supplement: Vitamin D3 placebo; Dietary supplement: Vitamin D3 .
Active Comparator: Vitamin D placebo + fish oil; Drug: omega-3 fatty acids (fish oil) Omacor, 1 capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]). Dietary Supplement: Vitamin D3 placebo Vitamin D placebo	Dietary supplement: Fish oil placebo; Drug: omega-3 fatty acids (fish oil)
Active Comparator: Vitamin D placebo + fish oil placebo; Dietary Supplement:Vitamin D3 placebo Vitamin D placebo Dietary Supplement: Fish oil placebo Fish oil placebo	Dietary supplement: Fish oil placebo; Dietary supplement: Vitamin D3 placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Anemia	We will compare the number of participants who took vitamin D supplements who developed anemia and the number of participants who did not take vitamin D who developed anemia to current rates of development of anemia in the U.S. We will further examine whether the effect of vitamin D supplementation on anemia risk varies by race/ethnicity, gender, or baseline levels of 25(OH)D.	2 years
Long-term Changes in Blood Protein Levels	We will examine the samples from the 900 boston participants and determine whether vitamin D supplementation affects long-term changes in hemoglobin, red blood cell (RBC) indices, hepcidin, and erythropoietin (EPO) levels. These protein levels will be assessed in both anemic and non-anemic individuals in fresh samples at baseline [pre-randomization] and at 2 years of follow-up post-randomization.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Anemia	We will compare the number of participants taking fish oil supplements who developed anemia and the number of participants not taking fish oil supplements who developed anemia to the current rates of development of anemia in the U.S. We will also study the number participants diagnosed with anemia over 4 years of follow-up and whether the effect of taking fish oil supplements on anemia risk varies by race/ethnicity, gender, or baseline levels of omega-3 fatty acid.	2 years
Long-term Changes in Protein Levels	We will examine the samples collected from the 900 Boston participants and determine whether fish oil supplementation affects long-term changes in hemoglobin, red blood cell(RBC) indices, hepcidin, and erythropoietin (EPO) levels. These protein levels will be assessed in both anemic and non-anemic individuals in fresh samples at baseline [pre-randomization] and at 2 years of follow-up post-randomization.	2 years

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Center for Complementary and Integrative Health (NCCIH); Office of Dietary Supplements (ODS)
• Investigators: Principal Investigator: Nancy Berliner, MD, Brigham and Women's Hospital

Publications and helpful links

Helpful Links

• Welcome to the VITAL Study Website

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2012
• Primary Completion (Estimated): December 28, 2025
• Study Completion (Estimated): December 28, 2025

Study Registration Dates

• First Submitted: June 29, 2012
• First Submitted That Met QC Criteria: June 29, 2012
• First Posted (Estimated): July 3, 2012

Study Record Updates

• Last Update Posted (Estimated): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: anemia; primary prevention; vitamin D3; omega-3 fatty acids; fish oil
• Additional Relevant MeSH Terms: Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia; Fatty Acids; Lipids; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Fatty Acids, Unsaturated; Oils; Dietary Fats; Fats; Dietary Fats, Unsaturated; Cholestenes; Cholestanes; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Cholecalciferol; Fish Oils; Fatty Acids, Omega-3
• Other Study ID Numbers: 2012P001526