- Vitamin D and autoimmune rheumatic diseases
- The mechanisms of vitamin D immunomodulation
- Vitamin D And Inflammation
- WHAT IS INFLAMMATION?
- MARKERS OF INFLAMMATION
- WHAT IS C-REACTIVE PROTEIN?
- WHY SHOULD YOU TEST YOUR CRP LEVELS?
- WHY SHOULD YOU TEST YOUR VITAMIN D LEVELS?
- Low Levels Of Vitamin D In Patients With Autoimmune Disease May Be Result, Not Cause, Of The Disease
- Study Finds Vitamin D, Fish Oil Do Not Curb Inflammation
- 6 Inflammation-Fighting Vitamins
Vitamin D and autoimmune rheumatic diseases
Vitamin D is classified as a secosteroid in which one of the rings has been broken, in this case by ultraviolet B sunlight, and the main source of vitamin D is de novo synthesis in the skin. Although vitamin D is consumed in food, dietary intake alone is often insufficient, supplying only 20% of the body's requirements.
In recent years, the discovery of the vitamin D receptor (VDR) in the cells of the immune system and the fact that several of these cells produce the vitamin D hormone suggested that it could have immunoregulatory properties.
However, vitamin D insufficiency is emerging as a clinical problem of global proportions and epidemiology has linked vitamin D status with autoimmune disease susceptibility and severity .
Therefore, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] the biologically active metabolite of Vitamin D3, not only regulates bone and calcium metabolism but also exerts immunomodulation via the nuclear VDR expressed in antigen-presenting cells and activated T/B cells . In particular, this regulation is mediated through interference with nuclear transcription factors such as NF-AT and NF-κB or by direct interaction with vitamin D responsive elements in the promoter regions of cytokine genes.
The mechanisms of vitamin D immunomodulation
Dendritic cells (DCs) are primary targets for the immunomodulatory activity of 1,25(OH)2D3, as indicated by inhibited DC differentiation and maturation, leading to down-regulated expression of MHC-II, costimulatory molecules (CD40, CD80 and CD86) and decreased production of IL-12. Moreover, 1,25(OH)2D3 enhances IL-10 production and promotes DC apoptosis. Together, these effects of 1,25(OH)2D3 inhibit DC-dependent T-cell activation  (Fig. 1).
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Mechanisms involved in vitamin D modulation of the immune responses. DCs are primary targets for the immunomodulatory activity of 1,25(OH)2D3, as indicated by inhibited DC differentiation and maturation, together with inhibition of differentiation of monocyte precursors into immature DCs.
1,25(OH)2D3 suppresses Th1 (and Th17)-driven cytokine responses, induces Treg cells, induces IL-4 production (Th2) and enhances NKT-cell function. Differentiation and maturation of B cells is also inhibited. Th are CD4+ helper cell subsets (Th1, Th2, Th3-Treg, Th17) originating from naïve T cell (Th0).
Thin arrows (left) indicate cytokines that induce differentiation of Th0 cells and thicker arrows (right) indicate cytokines produced by activated Th cell subsets. All T cells that have been tested express the VDR. B cells and NKT cells are also reported. The yellow circles indicate the cytokines/activities inhibited by vitamin D.
On the contrary, the green circles indicate the cytokines enhanced by vitamin D.
In particular, the active synthesis of 1,25(OH)2D3 seems to exert an autoregulatory function by inhibiting the differentiation of monocyte precursors into immature DCs and the subsequent ability of the immature DCs to undergo terminal differentiation in response to maturation stimuli  (Fig. 1).
Tolerogenic DCs induced by a brief treatment with 1,25(OH)2D3 or its analogues can induce CD4+CD25+ T regulatory (Treg) cells that are able to mediate transplantation tolerance and arrest the development of autoimmunity (i.e. autoimmune diabetes) .
Tolerogenic DCs may not always be necessarily involved in the generation of Treg cells by VDR agonists, however, and a combination of 1,25(OH)2D3 and dexamethasone has been shown to induce naïve CD4+ T cells (Th0) to differentiate in vitro into IL-10-producing Treg cells, even in the absence of antigen-presenting cells  (Fig. 1).
VDR agonists not only favour induction of CD4+CD25+ Treg cells and enhance their suppressive activity, but can also promote their recruitment at inflammatory sites. Furthermore, 1,25(OH)2D3 treatments induced natural killer (NK) T-cell functions in vitro and in vivo  (Fig. 1).
NKT cells are early innate regulatory cells that can alter the outcome of autoimmunity. Therefore, two types of cells are induced by 1,25(OH)2D3, the Treg and the NKT cells; induction of these regulatory cells and direct inhibition of Th1 cells are the mechanisms by which 1,25(OH)2D3 suppresses experimental autoimmunity .
In addition, treatment with VDR agonists inhibits the T-cell production of IL-17, a pro-inflammatory cytokine that is produced by pathogenic T cells (Th17) in various models of organ-specific autoimmunity in the brain, heart, synovium and intestines  (Fig. 1).
Interestingly, IL-17 production is sustained by IL-23, an IL-12 family member consisting of p19 and p40 chains, the latter of which is strongly inhibited by VDR agonists .
Recently, 1,25(OH)2D3 treatment induced a significant inhibition of normal lymphoid cell progenitors growth of both T and B lineage and inhibited significantly also the growth of malignant B-cell lineage lymphoid progenitors, without inducing cytotoxic effect .
More recently, by testing the effects of 1,25(OH)2D3 on B-cell responses, it was found that it inhibited the ongoing proliferation of activated B cells and induced their apoptosis, whereas initial cell division was unimpeded  (Fig. 1).
The generation of plasma cells and post-switch memory B cells was significantly inhibited by 1,25(OH)2D3 although the up-regulation of genetic programmes involved in B-cell differentiation was only modestly affected.
B cells expressed mRNAs for proteins involved in vitamin D activity, including 1α-hydroxylase, 24-hydroxylase and the VDR, each of which was regulated by 1,25(OH)2D3 and/or activation.
Interestingly, 1,25(OH)2D3 up-regulated the expression of p27, but not of p18 and p21, which may be important in regulating the proliferation of activated B cells and their subsequent differentiation in plasma cells .
The net effect of the vitamin D endocrine system on the immune response is an enhancement of innate immunity coupled with multifaceted regulation of adaptive immunity .
Epidemiological evidence indicates a significant association between vitamin D deficiency and an increased incidence of autoimmune diseases, and clarification of the physiological role of endogenous VDR agonists in the regulation of autoimmune responses will support the pharmacological VDR agonists for use in the clinic. The anti-proliferative, pro-differentiative, immunomodulatory and anti-inflammatory properties of synthetic VDR agonists could be exploited to treat a variety of autoimmune rheumatic diseases, from RA to SLE, and possibly also multiple sclerosis, type 1 diabetes or IBDs .
Low serum levels of vitamin D3 might be partially related, among other factors, to prolonged daily darkness (reduced activation of the pre-vitamin D by the ultraviolet B sunlight), different genetic background (i.e.
vitamin D receptor polymorphism) and nutritional factors, and explain to the latitute-related prevalence of autoimmune diseases such as RA, by considering the potential immunosuppressive roles of vitamin D .
Treatment of vitamin D deficiency could be particularly important in SLE patients due to concomitant insults on their tissues such as bone, and in view of the discovered immunomodulatory effects exerted by vitamin D .
Regarding RA, a recent study evaluated the association of dietary and supplemental vitamin D intake with RA incidence . Through 11 yrs of follow-up, 152 cases of RA were validated against medical records.
Greater intake (highest versus lowest tertile) of vitamin D was inversely associated with risk of RA (P for trend = 0.05). Inverse associations were apparent for both dietary (P for trend = 0.16) and supplemental (P for trend = 0.03) vitamin D.
No individual food item, high in vitamin D content and/or calcium was strongly associated with RA risk, but a composite measure of milk products was suggestive of an inverse association with risk of RA (P for trend = 0.06).
In conclusion, greater intake of vitamin D may be associated with a lower risk of RA in older women, although this finding is hypothesis-generating .
An older study in 19 RA patients evaluated the effects of oral α-calcidiol 2 μg/day added to regular drug regimen .
After 3 months, high-dose oral α-calcidiol therapy showed a positive effect on disease activity in 89% of the patients (45% or nine patients with complete remission and 44% or eight patients with a satisfactory effect). Only two patients (11%) showed no improvement, but no new symptoms occurred. No side-effects were observed.
These results suggest that α-calcidiol is a powerful immunomodulatory agent with fairly low hypercalcaemic activity. Clinical improvement was strongly correlated with the immunomodulating potential of this agent; in fact, dual effects on lymphocyte proliferation and apoptosis according to the prior cell activation state were observed.
α-Calcidiol could therefore possibly be used as an adjunct therapy with DMARDs in patients with active RA .
Therefore, greater intake of vitamin D has been associated with a lower risk of RA but low serum vitamin D together with higher prevalence of RA seem common among North European people when compared with Southern Europe. A recent study evaluated serum 25(OH)D levels in female RA patients from North (Estonia) and South (Italy) Europe and to correlate them with the disease activity score (DAS28) during winter and summer .
The 25(OH)D levels were found significantly higher in south vs north (P = 0.0116) both in winter and in summer time. Differences were observed also in controls. The variations (increase) of 25(OH)D levels between winter and summer were found to be significant (P = 0.0005) in both south and north. Differences were also observed in controls.
No significant differences were found concerning 25(OH)D levels between RA patients and their controls in either country. Interestingly, a significant negative correlation between 25(OH)D and DAS28 was found in summer only in south (r = −0.57, P < 0.0001) and in winter in north (r = −0.40, P < 0.05).
In conclusion, significantly lower 25(OH)D serum levels were observed in RA patients from north vs south Europe with a circannual rhythm in winter and summer time.
In addition, 25(OH)D values showed a significant correlation (negative) with RA clinical status (DAS28) in both North and South European RA patients, suggesting possible effects of vitamin D among other factors on disease activity .
More recently, it was investigated if serum vitamin D metabolites may be inversely associated with current disease activity, severity and functional disability in patients with early RA .
At baseline, there was an inverse relationship between 25(OH)D levels and the tender joint count, DAS28 score and HAQ score. The only inverse relationship with 1,25(OH)2D3 was with the HAQ score. Each 10-ng/ml increase in the level of 25(OH)D was associated with a decrease in the DAS28 score of 0.3 and in the CRP level of ∼25%.
At 1 yr, the only significant result was an inverse association between baseline vitamin D metabolite levels and the HAQ score; that is, those with higher metabolite levels had lower HAQ scores.
These data provide further support that vitamin D plays an immunomodulatory role in inflammatory arthritis and, if confirmed, the vitamin D supplementation should be also examined in early RA .
A number of recent studies have highlighted the association between SLE and vitamin D deficiency. Vitamin D deficiency skews the immunological response towards loss of tolerance. Adding vitamin D in vitro reverses immunological abnormalities characteristic of SLE.
Serum 25(OH)D levels between recently diagnosed SLE cases and matched controls, as well as disease characteristics in relationship to 25(OH)D among cases, were recently studied .
Data from a population-based cohort of 123 recently diagnosed SLE patients and 240 controls were used. A trend towards lower 25(OH)D levels in SLE cases compared with controls, which was statistically significant in Caucasians (P = 0.
04), controlling for age, sex, season and smoking was detected. Overall, 67% of the subjects were vitamin D deficient, with mean levels significantly lower among African Americans (15.9 ng/ml) compared with Caucasians (31.3 ng/ml).
Critically low vitamin D levels (
Vitamin D And Inflammation
It can lurk in your body for months and years – relentlessly damaging your tissues and organs – and it goes by the name “chronic inflammation.” Because chronic inflammation can quietly exist at a low level, its presence in your body isn’t always blatantly obvious.
Nevertheless, chronic inflammation can slowly-but-surely chip away at your health and increase your risk for various diseases – including heart disease, diabetes, cancer, and Alzheimer’s.
Here’s the good news though: you can test for chronic inflammation in your body with a simple use-it-at-home kit.
You can test for chronic inflammation in your body with a simple use-it-at-home kit.
That kit is EverlyWell’s Vitamin D and Inflammation Test – which checks your blood for key markers of inflammation.
But what exactly is inflammation – and what markers of inflammation does this test detect? Here, we’ll tackle each of these questions in turn.
WHAT IS INFLAMMATION?
Inflammation is what happens when your body responds to threats microbial invaders, poisonous chemicals, and physical injuries. Signs of acute inflammation – in other words, short-term inflammation – include redness and swelling at the affected part of your body.
Acute inflammation is something you’ve ly experienced on-and-off throughout your entire life. For example, have you ever had a sore throat induced by a pesky cold? If so, it was because of inflammation in your throat area.
Have you ever had a sore throat induced by a pesky cold? If so, it was because of inflammation in your throat area.
In more detail, your throat became swollen because of the lymph nodes located there. Lymph nodes contain white blood cells that filter the lymphatic fluid looking for foreign invaders bacteria and viruses – when they find them, they attack.
When you have a cold, your lymph nodes often swell because of the inflammation caused by the white blood cells killing the invaders.
So while your sore throat may have been quite irksome to you, it was actually an indication that your immune system was actively fighting against hordes of pathogens.
The last time you had a cold, the inflammation in your throat ly subsided after a few days (and you no longer dreaded the act of eating food or gulping down beverages). However, inflammation doesn’t always fade away after a short time. When it persists for months and years, it’s called chronic inflammation.
Inflammation doesn’t always fade away after a short time. When it persists for months and years, it’s called chronic inflammation.
Chronic inflammation is a totally different beast than acute inflammation. While acute inflammation is a protective response by your body, chronic inflammation can be incredibly destructive.
It occurs when your body’s immune system fails to eradicate a threat – such as a bacterial infection – or when you have too many pro-inflammatory substances entering your body and not enough anti-inflammatory substances, vitamin D, to control the inflammation.
For example, when a certain type of bacteria – known as H. pylori – infects your stomach lining, you might get gastritis (inflammation of the stomach lining). At first, this inflammation may be acute and relatively short-lasting. But if the infection isn’t stopped, the inflammation can become chronic – increasing the risk of stomach cancer by up to 75%!
Chronic inflammation can also result from autoimmune disorders: your immune system malfunctions and goes to war against healthy tissue – unaware that your healthy tissue is not a threat.
MARKERS OF INFLAMMATION
Whenever inflammation occurs somewhere in your body – whether acute or chronic – the affected tissue sends a signal to your liver (via small molecules).
This signal prompts your liver to unleash a flood of special molecules – dubbed “C-Reactive Protein” – into your bloodstream.
And, as it turns out, C-Reactive Protein is one of the markers measured by EverlyWell’s Vitamin D and Inflammation Test.
WHAT IS C-REACTIVE PROTEIN?
Large amounts of C-Reactive Protein – or CRP – is released into your bloodstream as a response to inflammation, warning your body’s healthy tissues of a possible attack (perhaps from an army of pathogens). This gives your healthy cells time to muster their molecular defenses.
Since CRP molecules are rushed into your bloodstream whenever inflammation occurs, your blood’s CRP levels are a reliable indicator of inflammation in your body.
Because EverlyWell’s Vitamin D and Inflammation kit makes use of a high-sensitivity CRP test (hs-CRP), it can spot very slight elevations of CRP in your blood – detecting even subtle, stealthy levels of inflammation in your body.
WHY SHOULD YOU TEST YOUR CRP LEVELS?
Chronic inflammation is a warning sign that something’s wrong in your body. Early clues of chronic inflammation include persistent pain in your joints or muscles, high blood pressure, and a feeling of lethargy that just doesn’t seem to go away.
Early clues of chronic inflammation include persistent pain in your joints or muscles, high blood pressure, and a feeling of lethargy that just doesn’t seem to go away.
Chronic inflammation is also connected with more extreme health conditions, such as arthritis, inflammatory bowel disease, atherosclerosis, and cancer – to name just a few.
And chronic inflammation can sneak up on you, too: you won’t always know you have it until it seriously harms your health.
But you can take measures to protect against that possibility – checking your CRP levels with EverlyWell’s Vitamin D and Inflammation Test.
As its name implies, EverlyWell’s Vitamin D and Inflammation Test also checks your blood’s vitamin D levels. So what is vitamin D – and what does it have to do with inflammation?
Vitamin D is a fat-soluble compound that’s created when sunlight strikes your skin. Its importance to your wellbeing can hardly be overstated.
For instance, vitamin D helps your body use calcium much more effectively, contributing to a healthier, stronger skeletal system. Vitamin D also supports the immune system.
There’s also evidence that low levels of vitamin D are linked with higher levels of inflammation – which highlights the important role vitamin D plays in shaping your health.
Vitamin D is a fat-soluble compound that’s created when sunlight strikes your skin.
Many people don’t get enough vitamin D, partially because people are less exposed to sunlight today than in the past. In fact, vitamin D deficiency is so rampant – close to half of the world’s population have insufficient vitamin D levels – that some have called it an “epidemic.”
So checking your vitamin D levels is not only important in and of itself (given the high rates of vitamin D deficiency), but it’s also a useful way to discover if you have inflammation in your body.
WHY SHOULD YOU TEST YOUR VITAMIN D LEVELS?
Your body might try to tell you that you’re deficient in vitamin D by excessive sweating and fatigue. Other signs of vitamin D deficiency include depression and weakness.
Vitamin D deficiency can lead to osteoporosis – where your bones wear away (without getting repaired) and become brittle (which makes them break more easily). Young children who are vitamin D deficient can develop rickets. And, in pregnant women, low levels of vitamin D appear to increase rates of miscarriage.
For these reasons – coupled to the fact that a lot of people are vitamin D deficient – testing your vitamin D levels can be a crucial first step towards greater well-being.
Testing your vitamin D levels can be a crucial first step towards greater well-being.
What’s more, your vitamin D levels can help reveal inflammation in your body – so when you check both your vitamin D and CRP levels, you can glean especially powerful insights on the state of your health.
Chronic inflammation is often a sign that your health is, in some way, at risk. Left unchecked, it can put your wellbeing in grave danger. Fortunately, however, you can test for inflammation by checking your CRP and vitamin D levels with EverlyWell’s Vitamin D and Inflammation Test.
Test for inflammation by checking your CRP and vitamin D levels with EverlyWell’s Vitamin D and Inflammation Test.
And after that? Consult with your healthcare provider to determine the next steps you can take to improve your health.
Low Levels Of Vitamin D In Patients With Autoimmune Disease May Be Result, Not Cause, Of The Disease
Deficiency in vitamin D has been widely regarded as contributing to autoimmune disease, but a review appearing in Autoimmunity Reviews explains that low levels of vitamin D in patients with autoimmune disease may be a result rather than a cause of disease and that supplementing with vitamin D may actually exacerbate autoimmune disease.
Authored by a team of researchers at the California-based non-profit Autoimmunity Research Foundation, the paper goes on to point out that molecular biologists have long known that the form of vitamin D derived from food and supplements, 25-hydroxyvitamin D (25-D), is a secosteroid rather than a vitamin. corticosteroid medications, vitamin D may provide short-term relief by lowering inflammation but may exacerbate disease symptoms over the long-term.
The insights are molecular research showing that 25-D inactivates rather than activates its native receptor – the Vitamin D nuclear receptor or VDR.
Once associated solely with calcium metabolism, the VDR is now known to transcribe at least 913 genes and largely control the innate immune response by expressing the bulk of the body's antimicrobial peptides, natural antimicrobials that target bacteria.
Written under the guidance of professor Trevor Marshall of Murdoch University, Western Australia, the paper contends that 25-D's actions must be considered in light of recent research on the Human Microbiome.
Such research shows that bacteria are far more pervasive than previously thought – 90% of cells in the body are estimated to be non-human – increasing the lihood that autoimmune diseases are caused by persistent pathogens, many of which have yet to be named or have their DNA characterized.
Marshall and team explain that by deactivating the VDR and subsequently the immune response, 25-D lowers the inflammation caused by many of these bacteria but allows them to spread more easily in the long-run.
They outline how long-term harm caused by high levels of 25-D has been missed because the bacteria implicated in autoimmune disease grow very slowly.
For example, a higher incidence in brain lesions, allergies, and atopy in response to vitamin D supplementation have been noted only after decades of supplementation with the secosteroid.
Furthermore, low levels of 25-D are frequently noted in patients with autoimmune disease, leading to a current consensus that a deficiency of the secosteroid may contribute to the autoimmune disease process. However, Marshall and team explain that these low levels of 25-D are a result, rather than a cause, of the disease process.
Indeed, Marshall's research shows that in autoimmune disease, 25-D levels are naturally down-regulated in response to VDR dysregulation by chronic pathogens.
Under such circumstances, supplementation with extra vitamin D is not only counterproductive but harmful, as it slows the ability of the immune system to deal with such bacteria.
The team points out the importance of examining alternate models of vitamin D metabolism. “Vitamin D is currently being recommended at historically unprecedented doses,” states Amy Proal, one of the paper's co-authors. “Yet at the same time, the rate of nearly every autoimmune disease continues to escalate.”
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Study Finds Vitamin D, Fish Oil Do Not Curb Inflammation
Dietary supplements containing vitamin D and fish oil with omega-3 fatty acids do not reduce signs of systemic inflammation linked to many chronic diseases, according to a recent study. This study was part of a larger trial that found these supplements did have some benefit in healthy adults, including decreased risk of heart attack and death from cancer.
Inflammation is how the body tells itself to heal and repair damaged tissue or defend itself against infections.
Chronic, systemic inflammation occurs when the body constantly releases signals meant to activate the immune system, even when there is no injury or infection.
Systemic inflammation is a significant factor in cardiovascular disease, diabetes, autoimmune disorders, and other chronic conditions.
Some advertisements for vitamin D and fish oil supplements claim they reduce systemic inflammation, potentially leading to benefits such as reduced risk of chronic diseases.
However, evidence of vitamin D and fish oil supplements' ability to reduce inflammation has been mixed and based mostly on small studies in which researchers observed the effects of supplements rather than comparing them directly to a placebo (inactive pill).
“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,” said Karen Costenbader, MD, MPH, a researcher in the VITamin D and OmegA-3 TriaL (VITAL) study.
Un earlier studies, VITAL is a large, randomized controlled trial. Randomized controlled trials are thought to provide more reliable evidence than studies based solely on observation. Randomized means that participants are distributed between multiple treatment groups, and controlled means that treatments are compared to a placebo, which has no effect.
VITAL researchers studied 1,561 healthy participants—including men age 50 and older and women age 55 and older—who they assigned to four different treatments. One group took just vitamin D, the second took only fish oil, the third took a combination of the two, and the fourth group took a placebo.
The researchers measured participants' vitamin D and omega-3 fatty acids blood levels at the beginning of the study and compared them to the values measured at the end of the study. They also compared participants' blood levels of proteins that rise with systemic inflammation.
These proteins were interleukin-6 (IL-6), tumor necrosis factor-receptor 2 (TNFR 2), and high-sensitivity C-reactive protein (hsCRP).
After a year, the researchers found that vitamin D blood levels rose by 39% in participants who took vitamin D and omega-3 fatty acid blood levels rose by 55% in participants who took fish oil supplements.
However, the levels of the inflammatory proteins stayed relatively stable or had only minor changes after a year.
In contrast, if the supplements were beneficial for inflammation, the expected result would be a significant drop in the level of the inflammatory proteins.
VITAL researchers noted that although many vitamin D and omega-3 fatty acid supplements are available, they only tested one formulation and dose of each.
Participants also were generally healthy, which means the study was not designed to evaluate whether these supplements can benefit people diagnosed with conditions that cause acute or chronic inflammation (e.g., autoimmune disorders, cancer).
“Vitamin D and marine omega-3 fatty acids are widely consumed supplements advertised to prevent disease and reduce systemic inflammation. Their purported health benefits have received enormous attention in the medical and popular presses,” Costenbader said.
However, “in this study … neither vitamin D 2000 IU per day nor [omega-3 fatty acid supplements] reduced systemic inflammation biomarkers over one year.
” As a result, “it is unly that these supplements, taken widely in the general population, have major anti-inflammatory effects,” she added.
The recent findings come a larger study—involving over 25,000 participants—of whether vitamin D and fish oil can help prevent disease in generally healthy men and women.
Overall, the larger study suggests that vitamin D does not lower the risk of cancer, heart attack, and stroke, but does appear to be associated with fewer deaths related to cancer.
The study also indicated that fish oil supplements are associated with a reduced risk of heart attack, especially for African Americans, and reduced risk of cancer in people who do not eat much fish.
Results from studies VITAL provide solid evidence for consumers wanting to more clearly understand what supplements will and will not do for their health.
wise, healthcare practitioners have reliable data they can point to when asked by their patients about the benefits, or lack of benefits, of taking supplements.
In this case, vitamin D and fish oil are not associated with decreased systemic inflammation in healthy adults, but they may have other health benefits that consumers can consider.
6 Inflammation-Fighting Vitamins
Research has pointed to certain vitamins with anti-inflammatory compounds. These vitamins can be acquired in supplement form and by eating foods naturally containing these vitamins.
Here is a list of six vitamins that possess anti-inflammatory properties, and foods that are rich sources of them.
Verywell / JR Bee
Studies have found vitamin A can keep the immune system from overacting and causing inflammation. Vitamin A is available in two forms: Beta-carotene is a provitamin that converts vitamin A in the body and vitamin A is an antioxidant that protects the body against free radicals. Diets rich in beta-carotene and vitamin A can help to reduce inflammation.
Foods rich in vitamin A include carrots, dandelion, kale, collard greens, spinach, and a wide variety of leafy vegetables.
People with low vitamin B6 will have high C-reactive proteins, another compound responsible for inflammation, especially in autoimmune diseases such as rheumatoid arthritis. To reduce inflammation and increase vitamin B6, try consuming foods high in B vitamins, including kale, bell peppers, and mushroom, cantaloupe, tuna, and poultry.
One Italian study finds even low doses of folic acid (also known as folate, another B vitamin) supplementation taken daily and for short periods can reduce inflammation.
Food sources of folate include black-eyed peas, dark leafy greens, asparagus, and liver.
Vitamin C is known for helping keep the immune system healthy and functioning well. Moreover, research shows vitamin C can get rid of free radicals responsible for inflammation. Vitamin C, B vitamins, may also help lower C-reactive proteins. Supplements are helpful, but it is always best to try to get vitamin C from your diet.
To get more vitamin C from your diet, eat a variety of fruits and vegetables, which are also loaded with antioxidants that can improve health and potentially lower risk for heart disease and cancers.
According to one report from Food & Nutrition Research, up to 41.6 percent of Americans are vitamin D deficient. Studies have long-established a connection between low vitamin D and a variety of inflammatory diseases. Further, researchers know that improving vitamin D can help reduce inflammation in the body.
Another report in The Journal of Immunology suggests specific molecular and signaling events are responsible for vitamin D’s ability to inhibit inflammation. Moreover, people with low levels of vitamin D can definitely benefit from vitamin D supplementation.
Vitamin D is naturally available from the sun, but not everyone can get all their vitamin D from the sun. Anyone who suspects their vitamin D levels are low should talk to their doctor about testing and supplementation.
The best food sources of vitamin D are fish, egg yolks, organ meats, and foods supplemented with vitamin D, including milk.
Vitamin E is another antioxidant vitamin, which means it can reduce inflammation. Results from a 2015 meta-analysis reported in the European Journal of Clinical Nutrition confirm vitamin E has anti-inflammatory properties and supplementation can be helpful to people living with inflammatory conditions.
Vitamin E is naturally found in nuts and seeds, including almonds and sunflower seeds. Many fruits and vegetables are also rich in vitamin E, including avocado and spinach.
One report in the journal, Metabolism finds vitamin K can reduce inflammatory markers and help with blood clotting and protecting bone health.
While vitamin K is necessary for bone health, most people do not get enough of it from their diets. Adult men should aim to take in 120 micrograms (mcg) daily of vitamin K, while women should aim for 90 mcg.
The daily recommended numbers are lower for children and infants.
There are two types of vitamin K: Vitamin K1 and K2.
Vitamin K1 is found in leafy vegetables, including kale, spinach, broccoli, and cabbage, while K2 is found in chicken, liver, and eggs.
Inflammation-fighting vitamins can be acquired from a variety of food sources, including vegetables, fruits, lean meats and fish, and vitamin-fortified foods. Even in supplement form, these vitamins can reduce inflammation without harsh side effects and are a viable option to NSAIDs (nonsteroidal anti-inflammatory drugs) and prescription anti-inflammatory medicines.
As a word of caution, starting any vitamin supplement without talking to a doctor is not a good idea. Moreover, vitamin supplements are not a substitute for medication.
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Rubin LP, Ross AC, Stephensen CB, Bohn T, Tanumihardjo SA. Metabolic effects of inflammation on vitamin A and carotenoids in humans and animal models. Adv Nutr. 2017;8(2):197-212. doi:10.3945/an.116.014167
Sproston NR, Ashworth JJ. Role of C-reactive protein at sites of inflammation and infection. Front Immunol. 2018;9:754. doi:10.3389/fimmu.2018.00754
Bird RP. The emerging role of vitamin B6 in inflammation and carcinogenesis. Adv Food Nutr Res. 2018;83:151-194. doi:10.1016/bs.afnr.2017.11.004
Chambial S, Dwivedi S, Shukla KK, John PJ, Sharma P. Vitamin C in disease prevention and cure: an overview. Indian J Clin Biochem. 2013;28(4):314-28. doi: 10.1007/s12291-013-0375-3
Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31(1):48-54. doi:10.1016/j.nutres.2010.12.001
Zhang Y, Leung DY, Richers BN, et al. Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol. 2012;188(5):2127-35. doi:10.4049/jimmunol.1102412
Saboori S, Shab-bidar S, Speakman JR, Yousefi rad E, Djafarian K. Effect of vitamin E supplementation on serum C-reactive protein level: a meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2015;69(8):867-73. doi:10.1038/ejcn.2014.296
National Institutes of Health. Vitamin K fact sheet for health professionals. Updated July 2019.
Aslam MF, Majeed S, Aslam S, Irfan JA. Vitamins: key role players in boosting up immune response-a mini review. Vitam Miner. 2017; 6:153. doi:10.4172/2376-1318.1000153
Harvard School of Public Health. Three of the B vitamins: folate, vitamin B6, and vitamin B12.
National Institutes of Health. Folate fact sheet for health professionals. Updated July 2019.
Palermo A, Tuccinardi D, D'Onofrio L, et al. Vitamin K and osteoporosis: myth or reality? Metabolism. 2017 May; 70:57-71. doi:10.1016/j.metabol.2017.01.032
Valentini L, Pinto A, Bourdel-Marchasson I, et al. Impact of personalized diet and probiotic supplementation on inflammation, nutritional parameters and intestinal microbiota – The “RISTOMED project”: Randomized controlled trial in healthy older people. Clin Nutr. 2015 Aug;34(4):593-602. doi:10.1016/j.clnu.2014.09.023