Vitamin d and fish oil

Study: How vitamin D and fish oil affect risk of heart attack, stroke and cancer

Credit: CC0 Public Domain

For years, it’s remained an open question: What effects do dietary supplements such as high doses of vitamin D or omega-3 fatty acids derived from fish oil have on the risk of diseases such as heart attack, stroke and cancer? While there have been hints along the way, until now, no randomized clinical trial of a general population, especially a racially diverse population, has been large enough to adequately address these questions. Brigham and Women’s Hospital investigators leading the VITamin D and OmegA-3 TriaL (VITAL) conducted a rigorous placebo-controlled trial over the course of 5.3 years, gleaning a treasure trove of information on the effects of both supplements. The team found that omega-3 fish oil reduced heart attack rates but did not affect risk of stroke or cancer. In addition, vitamin D did not significantly affect heart attack, stroke or cancer incidence but was associated with a decrease in cancer deaths that started one to two years after participants began treatment. Results from VITAL were presented by JoAnn Manson, MD, DrPH, chief of the Division of Preventive Medicine at the Brigham, at the American Heart Association Scientific Sessions 2018, and published simultaneously in the New England Journal of Medicine.

The VITAL study population was racially and ethnically diverse, and 20 percent of the participants were African American. The team found that the reduction of heart attack risk among those taking omega-3s was especially pronounced among African American participants, with a 77 percent reduction observed.

“VITAL is one of only a few randomized trials that has had a diverse study population, and African Americans have not been well studied in previous trials of omega-3 supplements. We found that omega-3 supplements were associated with a dramatic reduction in risk of heart attacks among African Americans in our study. If this finding is confirmed and replicated, it may point to a very promising approach to reducing coronary risk among African Americans,” said Manson. “We found that omega-3s were associated with a reduction in risk of heart attacks across our study population, especially among participants who had lower than average fish intake (less than 1 1/2 servings per week). In addition, VITAL results showed that with time, vitamin D supplements may lower risk of cancer death. We plan to follow these participants for the next several years to see if this signal becomes stronger.”

VITAL, a randomized, double-blind, placebo-controlled trial, enrolled 25,871 men and women age 50 and older from across the U.S., including 5,106 African Americans. Eligible participants had no history of cancer, heart attack, stroke, or other forms of cardiovascular disease at the time of enrollment.

While earlier trials have examined whether fish oil or other supplements may prevent heart attack or stroke in patients with a history of heart disease or at very high risk of such disease, VITAL is the first large trial of omega-3 fatty acids for primary prevention—that is, preventing the first occurrence—of heart disease in a general population.

VITAL was designed to test the independent effects of vitamin D and omega-3 supplements, as well as to test for synergy between the two. Participants were divided into four groups: vitamin D (2000 IU/day of vitamin D? ) plus omega-3s (1g/day of Omacor ); vitamin D plus placebo omega-3s; omega-3s plus placebo vitamin D; and placebos for both.

Researchers compared those who received active omega-3s with those who received placebo. After a median of five years of treatment, 805 participants had suffered a major adverse cardiovascular event, such as a heart attack or stroke (386 in the omega-3 group and 419 in the placebo group). While these rates did not statistically differ, VITAL found a significant 28 percent reduction in risk of heart attack among participants taking the omega-3 fatty acid supplements (145 cases in the omega-3 group and 200 in the placebo group). This effect was greater among people who had lower fish intake (a 40 percent reduction). No significant differences were seen for cancer outcomes.

The research team also examined the effect of vitamin D on cancer rates. A total of 1,617 participants were diagnosed with cancer by the end of the study; 793 had been taking vitamin D and 824 had been taking the placebo—a non-significant difference. Rates of specific forms of cancer—including breast, prostate and colorectal cancer—did not differ significantly between groups. However, when the team examined rates after participants had been taking supplements for at least two years, they found that cancer deaths were significantly reduced by 25 percent among those taking vitamin D. No differences were seen for cardiovascular outcomes with vitamin D.

No serious side effects, such as bleeding, high blood calcium levels, or gastrointestinal symptoms were found with either supplement. The two supplements did not appear to interact with each other or have synergistic effects. In addition to cardiovascular disease and cancer outcomes, VITAL will report on the effects of vitamin D and omega-3s on rates of diabetes, cognitive function, autoimmune disease, respiratory infections, depression and more in the months ahead.

“Over the next six months, we will have even more results to share that may help clinicians and patients understand the benefits and risks of taking omega-3 and vitamin D supplements,” said Manson. “Medical and public health authorities may look at the study results and decide if clinical guidelines should be updated. In the meantime, if you’re already taking one or both of these supplements, there’s no clear reason to stop. If you want to consider starting, our recommendation is to talk with your health care provider, but this does not need to be done on an urgent basis.”

Explore further

Big studies give mixed news on fish oil, vitamin D Journal information: New England Journal of Medicine Provided by Brigham and Women’s Hospital Citation: Study: How vitamin D and fish oil affect risk of heart attack, stroke and cancer (2018, November 12) retrieved 2 February 2020 from This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

Fish Oil, Vitamin D & Vitamin K: The Three Amigos for Bone & Heart Health
By Dr. Jen Morganti, NEEDS Education Director
Supplements can be a great way to boost your nutrient intake, especially on those days when your diet is less than perfect. But in some cases, certain vitamins are best taken together. The fact is, how you take a supplement may impact how much of the nutrients your body absorbs and receives.
What are Fat-Soluble Vitamins?
There are two types of vitamins— water-soluble and fat-soluble. Most are water-soluble, meaning they dissolve in water and can be excreted rapidly when the body doesn’t need them. In contrast, fat-soluble vitamins are best absorbed in fat and are stored in the body’s tissues when not in use. Fat-soluble vitamins are best absorbed into the blood stream when ingested with fats.
The Synergistic Relationship between Vitamins D and K
Many nutrients complement each other; vitamin D and vitamin K are a good example of this. They are both extremely important fat-soluble supplements when it comes to supporting our overall health. They both have the primary function of regulating calcium levels in the body through different means. Together, they provide a powerful combination that supports cardiovascular and bone health. Unfortunately, most of us do not get enough of these vitamins from our daily diets, so they should be considered in a daily supplement routine.
Vitamin D
Vitamin D is probably most wellknown for supporting optimal bone health and density. Some researchers believe vitamin D to be as critical to bone health as calcium, because D facilitates the absorption of calcium from food and supplements from the gastrointestinal tract into the blood stream. Vitamin D also helps maintain proper calcium levels in the blood, which facilitates the initial process of calcium entering into bones, muscle contraction, and other important functions.
Researchers have discovered that maintaining healthy vitamin D levels also provides a myriad of benefits for our overall health. Vitamin D supports heart health via its anti-inflammatory activities. Because of its anti-inflammatory properties, vitamin D may help prevent atherosclerosis, which is largely correlated with inflammation in blood vessels.
Beyond osteoporosis and cardiovascular disease, vitamin D deficiency has been linked with other health problems, including inflammation, depression, seasonal affective disorder, nervous system problems, rheumatoid arthritis, inflammatory bowel disease, and musculoskeletal pain. Vitamin D deficiency has also been shown to double the risk of having a heart attack, chest pain, stroke, and heart failure.
Vitamin K
Blood clotting is one of the most commonly known benefits of vitamin K. However, at optimal levels, researchers are discovering that vitamin K might be just as important to our overall health as vitamin D. There are two main forms of vitamin K—K1 and K2— and each has a unique purpose. K1 is related to the cardiovascular system in the sense that it activates and balances clotting factors to prevent excessive bleeding or hemorrhaging.
K2 is related to cardiovascular health because it helps keep blood vessels healthy and flexible. When arteries lose their flexibility, blood flow is constricted and the risk of heart disease increases dramatically. This is also known as aortic calcification because it’s caused by calcium deposits (calcification) in arteries (aortic). K2 preserves elastin, a protein the body produces that keeps blood vessels flexible and elastic.
If not enough K2 is present, excess calcium is deposited in arteries. K2 acts as a calcium diverter and activates a protein (MGP), which pulls the calcium out of blood vessels and shuttles the calcium into bone building actions. Vitamin K orchestrates the proper utilization of calcium in the body and without enough K2 there is an increased risk of both cardiovascular disease and osteoporosis.
Why Take Vitamins D and K in a Fish Oil Base?
The omega-3 fatty acids (also known as essential fatty acids) found in fish oil provides excellent support for the heart and vascular systems. Fish oil offers both EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). DHA is best known for its brain support. EPA is the direct precursor for the anti-inflammatory prostaglandins, which helps prevent blood vessel inflammation associated with atherosclerosis.
Although omega-3 fats might not be on the top of the list for proven bone support nutrients, they do support healthy calcium balance and positively impact the cells that build bone. Because fish oil is a fat, it promotes the absorption of vitamin D and vitamin K by preparing the body to secrete enzymes that promote fat absorption.
Best Dosages
Because vitamin D and vitamin K share a complementary working relationship for both bone and cardiovascular health, it makes sense to take them together in an oil base. Physicians generally recommend taking 2,000-10,000 IUs of vitamin D daily for optimal health. Vitamin D toxicity is rare when taken in the form of D3.
Vitamin K2 is safe, non-toxic, and the minimum recommended dose is 80 ug. It is best absorbed in a supplement form known as MK7. With the current trend of taking high doses of calcium and vitamin D, it’s critical to balance those with vitamin K2. Without K2, calcium levels can easily get out of balance which can lead to cardiovascular problems. Vitamin K2 and D3, combined with 2-3 grams of fish oil daily add up to a winning combination that decreases overall inflammation and prevents cardiovascular disease and osteoporosis.
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

BioMed Research International, Volume 2015 (2015), Article ID 109275, 12 pages. http://dx.doi. org/10.1155/2015/109275.

Fish oil and vitamin D supplements might offer some health benefits

In the journals

Published: March, 2019

Vitamin D and omega-3 fatty acid supplements have had mixed results when it comes to preventing heart attacks, strokes, and cancer in people who have already developed these problems or are at high risk for them. Yet a new study published online Nov. 10, 2018, by The New England Journal of Medicine found they may actually prevent these conditions among people who have never had these problems before.

Researchers recruited almost 26,000 people, ages 50 and older, who had no history of heart disease or cancer. The participants were divided into four groups. People in one group were given daily doses of 2,000 international units of vitamin D (an amount found to be linked to lower disease risk in observational studies) and 1 gram of a drug called Lovaza, which contained 840 milligrams of omega-3s (two to four times the amount in two servings of fish per week). The second group took vitamin D and a placebo, the third group took the omega-3s and a placebo, and the final group took two placebos. After more than five years, the researchers found that those given omega-3s were 28% less likely to suffer a heart attack compared with those given a placebo. Those who ate fewer servings of fish (less than the average of 1.5 servings per week) appeared to have a greater benefit from the additional omega-3s while those with higher fish intake had minimal benefit.

The study also found that those taking vitamin D supplements alone did not have lower rates of heart attack, stroke, or cancer. However, among people who later developed cancer, those who took vitamin D supplements for at least two years had a 25% lower chance of dying from their cancer compared with those who received a placebo.

Image: iStock

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Vitamin D and fish oil show promise in prevention of cancer death and heart attacks

Nearly 26,000 U.S. men and women participated in the nationwide VITAL clinical trial. After more than five years of study and treatment, the results show promising signals for certain outcomes. For example, while Omega-3 fatty acids (fish oil) showed only a small, but nonsignificant, reduction in the primary cardiovascular endpoint of major CVD events, they were associated with significant reductions in heart attacks. The greatest treatment benefit was seen in people with dietary fish intake below the cohort median of 1.5 servings per week but not in those whose intake was above that level. In addition, African-Americans appeared to experience the greatest risk reductions. The heart health benefits are now confirmed by recent meta-analyses of omega-3 randomized trials.

Similarly, vitamin D supplementation did not reduce major CVD events or total cancer incidence but was associated with a statistically significant reduction in total cancer mortality among those in the trial at least two years. The effect of vitamin D in reducing cancer death is also confirmed by updated meta-analyses of vitamin D trials to date.

“The pattern of findings suggests a complex balance of benefits and risks for each intervention and points to the need for additional research to determine which individuals may be most likely to derive a net benefit from these supplements,” says Dr. JoAnn Manson, lead author of the study from Brigham and Women’s Hospital, an affiliate of Harvard Medical School.

“With heart disease and cancer representing the most significant health threats to women, it is imperative that we continue to study the viability of options that prevent these diseases and help women survive them,” says Dr. Stephanie Faubion, NAMS medical director.

The Truth About Vitamin D and Fish Oil Supplements, According to a Huge New Study

Sorry to break it to you, but your trusty vitamin D and fish oil supplements probably aren’t going to prevent you from developing heart problems or cancer.

That’s according to a large, highly anticipated study called VITAL–which stands for Vitamin D and Omega-3 Trial–published in the New England Journal of Medicine and presented at this year’s American Heart Association Scientific Sessions. Given the popularity of these supplements, researchers have been eager to know their true benefits–and it’s not looking great.

Among nearly 26,000 healthy adults followed for around five years, supplementing with vitamin D or with fish oil did not lower cancer diagnoses or cardiovascular events–defined as strokes, heart attacks, or deaths from heart disease–compared to taking a placebo.

RELATED: More People Are Taking Vitamin D Than Ever. Here’s Why That Might Be Risky

The study participants–men age 50 and older and women 55 and up–took 2,000 international units of vitamin D and 1 gram per day of omega-3 fatty acids. VITAL is considered the largest such study of vitamin D and the only one like it around fish oil.

However, it’s not all bad news for vitamin D and fish oil. In people taking vitamin D supplements for at least two years, researchers found a 25% lower chance of death from cancer. And while fish oil didn’t reduce the rate of all those serious heart problems combined, it did seem to lower a person’s chance of a heart attack, specifically. That reduction was even higher in people who don’t get as much fish in their diets and in African-Americans.

“If this finding is confirmed and replicated, it may point to a very promising approach to reducing coronary risk among African-Americans,” lead author JoAnn Manson, MD, DrPH, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said in a statement. “We plan to follow these participants for the next several years to see if this signal becomes stronger.”

These so-called “secondary end points” in the scientific world will need to be researched more rigorously in studies specifically designed to tease out more details and should be interpreted with “caution,” according to an editorial published alongside the new study. Manson and her co-authors write that they plans to publish more results examining how the supplements may affect autoimmune disorders, diabetes, cognition, and other specific conditions.

RELATED: Getting Enough Vitamin D May Boost Your Workout

The researchers point out that there were no serious adverse events in the study, meaning there’s likely no major danger in continuing to take vitamin D or fish oil if you already do (although experts warn against taking sky-high doses of just about any supplement). Of course, vitamin D is still important for bone health–but keep in mind that what classifies as “adequate” or “deficient” vitamin D levels is still up for debate, and you may be getting plenty without supplements.

Complicating matters more is another study also published in the NEJM and presented at the AHA meeting. This study, named REDUCE-IT, found that people taking a 4-gram daily dose of a prescription drug made from a derivative of an omega-3 fatty acid did benefit from a lower risk of serious cardiovascular problems compared to people given a placebo. However, STAT News reported, because of a concern that the mineral oil in the placebo pill could have caused heart problems, the benefit to heart health may not be as impressive as it initially seemed.

As for what does help lower your risk for heart problems and cancer, make sure you’re eating a balanced, nutritious diet, getting plenty of exercise, and maintaining a healthy weight. And if you smoke, quitting can help reduce your risk of both heart disease and cancer.

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Neither vitamin D nor omega-3 supplements can prevent inflammation

Are omega-3 supplements as beneficial as researchers once believed? Not when it comes to inflammation, a new study suggests.

Share on PinterestOmega-3 supplements are not as beneficial for health as people once thought.

Recent studies show that taking supplements to increase vitamin D and omega-3 levels may not reduce systemic inflammation.

The new research, which drew from the VITAL study, aimed to determine the biomarker levels of several inflammation indicators in people either taking or not taking vitamin D and omega-3 fatty acid supplements, or fish oil.

After 1 year, the study found no marked difference in levels between the two groups.

Dr. Karen Costenbader — the director of the Lupus Program in the Division of Rheumatology, Inflammation, and Immunity at the Brigham and Women’s Hospital in Boston, MA — is the corresponding author of the study.

The results now appear in the journal Clinical Chemistry.

Why are markers of inflammation important?

Inflammation is a key prognostic marker of several life threatening conditions — especially those associated with aging and obesity.

These include cardiovascular disease, heart failure, osteoporosis, some neurodegenerative conditions (including Alzheimer’s disease), diabetes, and some cancers.

Many people use vitamin D supplements and fish oil to reduce systemic inflammation and help prevent the onset of such conditions.

However, the researchers behind the new study found that neither vitamin D nor fish oil can reduce systemic inflammation, and in some cases, inflammation markers were actually higher in people taking these supplements than in those not taking them.

Individually, these markers have pivotal roles in the onset of inflammation. Being able to detect increased levels of these markers in the blood can be a prognostic tool to inform healthcare professionals about a person’s levels of inflammation.

What was the purpose of the study?

Many people take vitamin D and fish oil supplements believing that they can help reduce inflammation. However, healthcare professionals may find it difficult to determine how to advise their patients about which supplements to take, and which dosages may be best.

This is because there is a lack of clinical trial data to inform treatment. The VITAL study aimed to provide the clinical data necessary to help healthcare professionals better inform their patients.

The ongoing VITAL study is a randomized, double-blind, placebo-controlled trial in which researchers investigate the effects of vitamin D, omega-3, or both on the levels of IL-6, TNFR2, and hsCRP in the blood.

For this research, the participants took 2,000 international units of vitamin D, 1 gram of omega-3, or both per day. Some received a placebo instead.

The scientists took an initial measurement at the beginning of the trial, which they compared with measurements they took a year later.

In the future, this trial will also investigate the effects of supplementation on the risks of cardiovascular disease and cancer.

What did the study find?

The results revealed that after 1 year of taking these supplements, blood levels of one type of vitamin D (25-OH) and one type of omega-3 (n-3 FA) were 39% and 55% higher in those taking the supplements, respectively, compared with those taking a placebo, in whom changes were minimal.

This suggests that the participants’ bodies were successfully absorbing the supplements.

Surprisingly, in those taking vitamin D supplements, levels of IL-6 were 8.2% higher.

Levels of hsCRP were 35.7% higher in people with lower baseline vitamin D, suggesting that those who take supplements because they have low vitamin D levels may actually be increasing their levels of this particular inflammatory marker.

Also, among those receiving omega-3, the levels of hsCRP did decline in those with lower baseline n-3 FA, but not in those with higher fish oil intake.

Conclusively, over 1 year of the study, neither supplement decreased the levels of biomarkers of inflammation.

“While the bottom line is that we didn’t see a reduction in markers of inflammation for those who took either supplement, we did see that people whose fish intake was low at baseline had a reduction in one of the biomarkers of inflammation.”

Dr. Karen Costenbader

“It will be interesting and important to see the results of future VITAL analyses, especially those that look at risk of diseases rather than biomarkers.”

Although these results seem to suggest no clinical benefit of taking supplementation to reduce systemic inflammation, there were a number of limitations to the trial.

For example, the cohort was a small snapshot of the initial recruits; the team tested only 1,500 of a potential 25,000. Had the cohort been larger, the results may have been clearer.

In addition, they only tested one form of vitamin D and one form of omega-3. Other formulations of these supplements could be more effective at decreasing systemic inflammation.

For these reasons, further investigation is necessary.

While previous studies have established that omega-3 and vitamin D are beneficial in improving cognitive function and behaviour, the exact mechanisms relating to this were unknown.

Co-author of the study, Dr Bruce Ames from the Children’s Hospital Oakland Research Institute (CHORI), suggests that omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and vitamin D work together to maintain healthy levels of serotonin in the brain.

“This synergy of omega-3 and vitamin D can be explained in part by their effects on the serotonin system: vitamin D regulates serotonin synthesis, EPA influences serotonin release, and DHA improves membrane embedded serotonin receptor accessibility,” ​says the study.

According to the researchers, low serotonin levels in normal individuals are associated with antisocial behaviour, increased uncontrolled aggressive behaviour and self-injury.

The study, published in the FASEB Journal​, also suggests that mental illnesses are less prevalent among women due to a protective effect provided by oestrogen, which increases brain serotonin synthesis.

Supplementation: ‘practical and relevant’​

According to Ames, many sufferers of mental illness are deficient in micronutrients, particularly vitamin D and omega-3 fatty acids.

“This may explain why supplementation with these essential micronutrients has been shown to be effective for treating symptoms associated with ADHD, bipolar disorder, schizophrenia, impulsive behaviour, depression, and obsessive compulsive disorder,” ​they say.

Do Omega-3 capsules need to be kept cool?

Keep this product cool. During periods of hot weather and/or while shipping to areas experiencing hot weather, the Omega-3 capsules may soften and stick together. While product efficacy is unaffected, consuming capsules that stick together, or which have melted together, may be unpleasant. For this reason, we suggest storing our Omega-3 product in a cool place and ordering enough of our Omega-3 product during cooler months so as to avoid possible heat-related shipping problems during hot weather.

What are EPA & DHA?

EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are considered the two most important omega-3 fatty acids. They are essential nutrients which means they must be obtained through your diet. EPA & DHA are found in many of the body’s organs and tissues and are vital to long-term health.

Why did Mannatech decide to add Vitamin D to its Omega-3 product?

Most importantly, and much like the case with omega-3s, an enormous amount of recent research and data suggests that not only are many people deficient in vitamin D, this deficiency may also be having a significant impact on long-term health. In addition, our omega-3 fish oil product perfectly complements vitamin D because both products are oil-based and can be combined into a single, easy-to-take gel capsule. Finally, vitamin D is a fat-soluble vitamin that can be better absorbed when taken or combined with another fat- or oil-based food or supplement, such as omega-3 fatty acids from fish oil.

What is vitamin D3 and how is it different from other forms of vitamin D?

Vitamin D has two basic forms, D2 (ergocalciferol) & D3 (colecalciferol). Both forms are natural and equally effective when consumed in moderate amounts. Vitamin D3, is naturally produced in your skin during exposure to direct sunlight and is thought to be the more beneficial form of vitamin D when consumed in higher amounts. Some animal products such as fish, eggs and fortified milk provide some vitamin D3 as well. Vitamin D2 is a plant-sourced form of vitamin D and is the form found in Mannatech’s PhytoMatrix and PhytoBurst products.

Many doctors and healthcare practitioners recommend large amounts of vitamin D, in some cases thousands of IUs per day. Why is this product 830 IU per serving?

While some experts recommend quantities of vitamin D that exceed the Institute of Medicine’s new recommended daily intake (RDI) of 600 IUs for adults up to 70 years of age, no current research indicates a single larger serving size that would be optimal for the population as a whole.

Is Omega-3 with Vitamin D3 suitable for vegetarians?

Currently, Omega-3 supplements that provide higher and balanced amounts of concentrated EPA and DHA are fish derived. Omega-3 with Vitamin D3 is derived from fish oil and lanolin and is contained within a capsule sourced from bovine gelatin. Because of this, we would not recommend for vegetarians.

Does Omega-3 with Vitamin D3 contain vitamin A?

Mannatech’s Omega-3 with Vitamin D3 does not contain a measurable amount of vitamin A. The oil in Omega-3 with vitamin D3 is made from whole fish, and the livers of these small cold water fish are very small, so there are only trace amounts of vitamin A in them. Once the oil goes through the molecular distillation, most of the remaining vitamins A is removed.

Why didn’t Mannatech use a plant-sourced omega-3, like flaxseed?

Plant-sourced omega-3s provide alpha linolenic acid (ALA), which has a shorter fatty acid chain than EPA and DHA. While ALA is healthy and beneficial, most of the benefits associated with consuming omega-3s are related to increased consumption of the longer-chain fatty acids EPA and DHA.

Vitamin D and Omega 3 supplements do not reduce risk of systemic inflammation: study

Credit: CC0 Public Domain

Vitamin D and marine omega-3 fatty acids—also known as fish oil—are purported to have many health benefits, including reducing systemic inflammation. Signals of systemic inflammation are tied to diseases of aging and obesity, including cardiovascular disease, heart failure, osteoporosis, diabetes mellitus, some cancers, and neurodegenerative diseases such as Alzheimer’s disease. While many consumers take supplements with the intention of lowering their inflammation and preventing disease, an analysis of the VITamin D and OmegA-3 TriaL (VITAL) by investigators at Brigham and Women’s Hospital indicates that neither vitamin D nor omega-3s were effective at reducing systemic inflammation. The team’s results are published in Clinical Chemistry.

“People commonly think that these supplements can prevent inflammatory diseases, but when a patient asks their doctor, ‘Should I take this supplement?’ doctors often don’t know what to advise because there haven’t been large scale clinical trials. VITAL provides a large dataset to address these questions,” said corresponding author Karen Costenbader, MD, MPH, director of the Lupus Program in the Division of Rheumatology, Inflammation and Immunity. “In this case, there isn’t a strong message that either supplement will reduce risk of systemic inflammation, at least not the biomarkers of disease.”

The VITAL study is a randomized, double-blind, placebo-controlled trial in which investigators tested the effects of supplements of vitamin D (2000 IU/day), omega 3s (1 gm/day) or both. For this analysis, Costenbader and colleagues tested levels of three known biomarkers of inflammation at the start of the trial and after one year of taking supplements or a placebo. They were interleukin-6 (IL-6), tumor necrosis factor-receptor 2, and high sensitivity C-reactive protein (hsCRP).

The team found that neither supplement reduced the biomarkers at one year. Surprisingly, among those taking the vitamin D supplement, instead of decreasing, IL-6 levels rose by 8.2 percent. The investigators also report that among participants who had lower fish intake at the start of the trial, hsCRP levels did decline for those taking the omega-3 supplement.

The authors note that they analyzed biomarkers for only a subgroup of the original trial’s population—approximately 1,500 of the over 25,000 participants—but they carefully selected a representative sample. In addition, VITAL only tested one formulation each of vitamin D and omega-3 supplements. A multitude of supplements are available.

“While the bottom line is that we didn’t see a reduction in markers of inflammation for those who took either supplement, we did see that people whose fish intake was low at baseline had a reduction in one of the biomarkers of inflammation,” said Costenbader. “It will be interesting and important to see the results of future VITAL analyses, especially those that look at risk of diseases rather than biomarkers.”

Explore further

Study: How vitamin D and fish oil affect risk of heart attack, stroke and cancer More information: Costenbader, K et al. “The Effects of One Year of Vitamin D and Marine Omega-3 Fatty Acid Supplementation On Biomarkers of Systemic Inflammation in Older U.S. Adults” Clinical Chemistry DOI: 10.1373/clinchem.2019.306902 Journal information: Clinical Chemistry Provided by Brigham and Women’s Hospital Citation: Vitamin D and Omega 3 supplements do not reduce risk of systemic inflammation: study (2019, November 7) retrieved 2 February 2020 from This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.

Vitamin D and Omega-3 Supplements for Preventing Cancer and Other Chronic Diseases

Q: What are the questions that the VITAL study intended to address?

DR. MANSON: Most previous studies of these dietary supplements have been observational, and we were interested in testing, in a large-scale randomized clinical trial setting, the effects of vitamin D and omega-3 fatty acid (FA) supplements on the risks of major chronic diseases, including cancer and cardiovascular disease. We wanted to have a “usual risk” population that was representative of the general public, age 50 and older and at typical risk of cancer and cardiovascular disease. All of the participants were free of these conditions at baseline.

Q: Could you tell us about the details of the study design?

DR. MANSON: The study included nearly 26,000 US men and women. The men were age 50 and older and the women were 55 and older, with racial and ethnic diversity. As I mentioned, the participants were free of cardiovascular disease and cancer at baseline. The duration of the trial was a median of 5.3 years, so this trial was longer than many of the previous randomized trials with these supplements. We used what is called a factorial design, which enabled us to look at the independent and joint effects of the two dietary supplements. Vitamin D was given at a dose of 2,000 international units (IUs), and the omega-3 FAs (which were in the form of a prescription medication called Lovaza in the United States) had 1 gram a day of the marine omega-3 FAs EPA and DHA .

Q: What were the major results? Were any of the findings particularly surprising?

DR. MANSON: The main results of the trial focused on the primary prespecified endpoints, which were total cancer incidence and major cardiovascular events (a composite of myocardial infarction, stroke, and cardiovascular mortality). There was not a significant reduction with either of the agents. With the omega-3 FAs, there were some promising findings for myocardial infarction. For vitamin D, we saw no significant reduction in total cancer incidence, but we did see a signal for a reduction in cancer death. During the overall treatment period of 5.3 years, we saw a statistically non-significant 17% reduction in cancer death, with a hazard ratio of 0.83. However, we had planned to account for a latency period by doing some analyses that excluded early follow-up. In an analysis that excluded the first 2 years of follow-up, we did see a signal for a reduction in cancer deaths that was statistically significant, a 25% reduction, as well as a non-significant 6% reduction in cancer incidence with vitamin D. And why might there be a reduction in cancer death but not cancer incidence?

This has been found in previous randomized clinical trials, including meta-analyses of earlier trials. There’s some evidence from laboratory and clinical studies that shows that vitamin D might modify tumor biology, such that it makes cancers less invasive and less likely to metastasize. This could lead to a reduction in the likelihood of death from cancer within a 5.3-year period, but not affect the initiation of cancer, which is a very long-term process. For the omega-3 FAs, we did not see any reduction in cancer incidence or cancer mortality. We did see some promising findings for myocardial infarction, a secondary prespecified endpoint—a 28% reduction. We also saw a hint that after excluding early follow-up and accounting for the latency period, there was a borderline increase in cancer incidence of 13% with the omega-3 FAs, which is statistically non-significant, but we plan to watch this closely over time in case any further increase in cancer incidence emerges. There was no increase in cancer deaths with the omega-3 FA supplementation.

In regard to vitamin D, it was not surprising that the signal was more for a reduction in cancer death than cancer incidence because that had been suggested by earlier randomized trials as well. However, we were surprised that there was a signal for a greater reduction in cancer among the participants who were average weight or lower. Those who were within a normal weight range did appear to benefit from vitamin D in terms of a reduction in cancer, but those who were overweight or obese did not. This suggests that perhaps the individuals who have a higher weight may need a larger dose of vitamin D or else they may have a type of resistance, similar to insulin resistance, with decreased bioactivity of vitamin D. This result needs further exploration, but it was very interesting and surprising to see such an interaction with body mass index for vitamin D and cancer.

Q: How do you interpret the VITAL study results and are there other similar trials that are ongoing or being planned, or is this trial unique?

DR. MANSON: There are other trials on vitamin D, but most are smaller or have tested lower doses. There is a large trial in Australia that has close to 20,000 participants, and the results should be reported over the next 2 years. Smaller trials on these supplements will report results over the next few years. Overall, the randomized clinical trials on vitamin D analyzed in meta-analyses have not suggested a reduction in the incidence of cancer, but have suggested a reduction in cancer mortality, so our findings are consistent with these meta-analyses. As the largest vitamin D trial, we should be able to contribute to additional meta-analyses and the updated results are likely to suggest an even stronger signal regarding cancer death. The longer follow-up of our study will be of great benefit. With the omega-3 FAs, there have been very few long-term randomized trials looking at cancer as a prespecified endpoint, so I think we will have important information from the longer follow-up of the VITAL trial.


Cara Anselmo, MS

Reducing Cancer Risk Through Diet

Nutrition guidance and choices can play a fundamental role in helping adults reduce their risks for cancer and other chronic diseases. A common thread throughout the nutrition research over many years is that eating a balanced, whole-foods diet is beneficial in disease risk reduction and, at the same time, highly unlikely to present health hazards. Consuming foods such as fish, olive oil, nuts, and seeds is a safe, effective, practical (and, many claim, delicious) way to get essential nutrients and fats.

Omega-3 fatty acids (FAs), in particular, have been proven to be beneficial. Back in 1991, one study determined that a fish oil diet inhibits colon cancer in mice. Several studies have revealed the benefits of omega-3 FA supplementation in women with breast and gynecological cancers, and a 2016 study showed the connection between consuming fish twice weekly and longevity.

There is little concern that a person will consume excess omega-3 fat from dietary sources, as compared with getting too much from supplements. As Manson points out, “mega-dosing”—or ingesting more than necessary of any given supplement, whether omega-3 FAs, vitamin D, or others—can pose dangers.

Although vitamin D is not found naturally in many foods, most adults can maintain adequate serum levels with appropriate sun exposure and/or dietary supplementation. Populations that seem to be at risk for low vitamin D include older adults, those who are home-bound or otherwise primarily indoors, persons with darker complexions such as African Americans, and those who are obese. Research suggests low vitamin D levels are associated not only with cancer and cardiovascular disease, but also diabetes, hypertension, metabolic syndrome, and cognitive decline. Mechanisms and causal relationships are still being elucidated. Nonetheless, it is safe to say that awareness of an individual’s serum vitamin D levels, and supplementing to prevent or correct a deficiency, is prudent. The bottom line is to get enough, but not too much, of any nutrient—ideally from foods, but from careful supplementation instead, if necessary.

Financial Disclosure: Ms. Anselmo has no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

1. Linder MA. A fish oil diet inhibits colon cancer in mice. Nutr Cancer. 1991;15:1-11.
2. Corsetto PA, Cremona A, Montorfano G, et al. Chemical–physical changes in cell membrane microdomains of breast cancer cells after omega-3 PUFA incorporation. Cell Biochem Biophys. 2012;64:45-59.
3. Rahman M, Veigas M, Williams PJ, Fernandes G. DHA is a more potent inhibitor of breast cancer metastasis to bone and related osteolysis than EPA. Breast Cancer Res Treat. 2013;141:341-52.
4. Khadge S, Thiele GM, Sharp JG, et al. Long-chain omega-3 polyunsaturated fatty acids decrease mammary tumor growth, multiorgan metastasis and enhance survival. Clin Exp Metastasis. 2018;35:797-818.
5. Gubbi S, Barzilai N, Crandall J, et al. The role of dietary patterns and exceptional parental longevity in healthy aging. Nutr Healthy Aging. 2017;4:247-54.

Ms. Anselmo has specialized in oncology nutrition since 2007. She is a Registered Dietitian Nutritionist at the Evelyn H. Lauder Breast Center of Memorial Sloan Kettering Cancer Center, New York, New York.

Q: What are the clinical implications of these results?

DR. MANSON: In terms of guidance regarding who should take supplements and who should not, we feel that we were able to demonstrate the safety over 5.3 years of this dose of vitamin D (2,000 IUs per day) and 1 gram per day of omega-3 FAs. We did not see significant side effects—there was no increased risk of hypercalcemia with this dose of vitamin D and no increased risk of bleeding with the omega-3 FAs. For patients who are already taking these supplements in similar doses, we don’t think the VITAL trial provides a strong reason for stopping these dietary supplements. However, we do think that it is important to caution against mega-dosing on these supplements because much higher doses of vitamin D have been linked to hypercalcemia and higher doses of omega-3 FAs can increase bleeding risk. This is an important warning, because there are individuals taking extremely high doses of these supplements.

For the omega-3 FAs, we did find that those who had lower fish consumption tended to benefit the most in terms of cardiovascular disease and heart attack risk. So, if someone has a very low fish intake despite encouragement to increase their consumption, and they’re at elevated risk for heart disease, they may be a candidate for an omega-3 FA supplement. However, we are not encouraging routine use of these supplements. Mostly we’re saying, stay tuned and we will have additional results in the next 6 to 12 months from several ancillary studies, as mentioned earlier, and we’ll have longer-term follow-up of the cohort. Some of the signals we saw may strengthen or weaken with longer follow-up. Both the longer-term follow-up and the ancillary studies will be very helpful in informing decision making. We expect that medical and public health authorities, over time, may look at the results from VITAL and other recent randomized trials, and assess whether the clinical guidelines for the use of these dietary supplements should be updated.

Q: What’s next for this study? You mentioned further follow-up. Are there additional analyses that you and your colleagues are now conducting, and are the participants still being followed to track outcomes?

DR. MANSON: We will be continuing to follow the participants for at least 2 years post-intervention. The treatment period ended December 31, 2017, and we will follow for an additional 2 years to see if any of these signals, such as the trend for a reduction in cancer death with vitamin D, will become stronger or weaker over time. We will also see if a significant reduction in cancer incidence emerges over time. Additionally, we will keep an eye on the omega-3 findings in relation to cancer. We plan to apply for a renewal grant and follow the participants for even longer, hopefully for at least 4 to 5 more years after this 2-year time point, allowing us to account more fully for latency of cancer and to have greater statistical power to look at the relationship between these dietary supplements and cancer.

We also have several ancillary studies that may help to inform the benefit-risk profile of these supplements. For example, we are looking at effects on diabetes, cognitive function, depression, and autoimmune diseases, and also testing their effect on numerous biomarkers, including telomere length and metabolomics, that may be of relevance to cancer, cardiovascular disease, and other chronic diseases.

Financial Disclosure: The VITAL study is supported by the National Institutes of Health, but study supplements were provided by Pharmavite and Pronova BioPharma/BASF Pharma.

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