Vitamin D Affects Genes for Cancer, Autoimmune Diseases
by  Lene Andersen
Tuesday, July 19, 2011

A study has linked vitamin D deficiency with an increased risk for cancer and autoimmune diseases like MS, lupus and rheumatoid arthritis (RA).

Vitamin D deficiency is connected with conditions such as rickets, which causes softness or weakening of the bones. However, this recent study by lead author Dr. Sreeram Ramagopalan from the Wellcome Trust Centre for Human Genetics at Oxford University and his colleagues further implicates vitamin D in other serious illnesses.

Vitamin D interacts with our genes through the vitamin D receptor. This receptor binds to the human genome at specific locations and in this way influences how a gene is expressed. In the study, the researchers used DNA sequencing technology to map vitamin D receptor binding throughout the human genome and found more than 2000 places where this binding happened. They discovered that the vitamin D receptor binding is enhanced at specific areas of the human genome that is associated with autoimmune diseases like type I diabetes, MS, RA and Crohn’s disease, as well as certain cancers, including leukemia and colorectal cancer. These illnesses are caused by a combination of genetic and environmental factors and vitamin D deficiency appears to be a major environmental factor in increasing the risk of developing such disorders. The study also found sites for vitamin D receptor binding in areas of the genome that contain genetic changes more common in people from Europe and Asia. This offered support for the theory that lighter skin and hair color evolved as populations moved to more northern and less sunny areas in order to maximize vitamin D absorption from the sun.

What does this mean in a practical sense? Dr. Ramagopalan is quoted as saying ‘There is now evidence supporting a role for vitamin D in susceptibility to a host of diseases. Vitamin D supplements during pregnancy and the early years could have a beneficial effect on a child’s health in later life.” Some countries (e.g., France) have started public health measures to help protect pregnant women and small children against vitamin D deficiency.

How to Assess Your Vitamin D Level and Increase Your Levels

It is estimated that 1 billion people worldwide do not get enough vitamin D. In the US, as many as 70% of children and adults are D deficient. The cause of this is a combination of not enough sun exposure and a diet low in vitamin D. Certain medications may also impact vitamin D absorption and kidney and liver disease can also lead to vitamin D deficiency.

Finding out whether your vitamin D levels are low is a matter of a simple blood test called the 25-hydroxy vitamin D test. Access to getting the test may become an issue, though. Due to vitamin D deficiency increasingly being implicated in many health conditions and the subsequent popularity of the test, Medicare has proposed vitamin D testing restrictions. In the Canadian province of Ontario, the provincial public health insurance OHIPdecided in late 2010 to only cover the cost (about $50) for a small number of medical disorders.

To increase your level of vitamin D, include more oily fish, such as salmon, mackerel and tuna in your diet. Egg yolks and mushrooms also contain vitamin D and you can choose cereal and milk fortified with vitamin D.

Vitamin D is also sometimes called the “sunshine vitamin” because your skin absorbs it through the rays of the sun. In fact, in the summer 15 minutes of sun exposure (without sunblock) can give you about 20,000 IU of vitamin D. On the other hand, it is generally not recommended that you expose yourself to sun without sunblock for longer periods of time, due to the risk of skin damage and skin cancer.

It’s a good idea to use vitamin D supplements. The Institute of Health has set the recommended dietary allowance to be 600 units a day, but this is generally accepted to be much too low. As well, with vitamin D there is no “one-size-fits-all” solution – how much you need depends on factors like how D deficient you are, which medical conditions you have, etc. It usually recommended that you should supplement by adding 1-2,000 IU of vitamin D per day, although people who are severely deficient or have certain medical conditions may take up to 5-10,000 IU per day. Vitamin D in liquid form, usually available in a health food store, has better absorption rates and are therefore recommended above vitamin D tablets.

The Many Benefits of Vitamin D

In the past several years, Vitamin D has been connected to benefits in a number of medical conditions. It has been known for a long time that it plays a crucial role in the absorption of calcium, which helps protect your bones from osteoporosis, but did you know Seasonal Affective Disorder is connected to vitamin D deficiency? As well, older adults who have low levels of vitamin D are more likely to become depressed.

Vitamin D also plays a role in the management of chronic pain, particularly musculoskeletal pain in conditions like fibromyalgia, RA and diabetic neuropathy. It’s quite common for people who live with chronic pain to have a vitamin D deficiency. Some doctors routinely test their patient’s vitamin D levels and include vitamin D supplements as part of the treatment plan.

The knowledge that vitamin D can not just make you feel better, but may also help lower the risk of cancer and autoimmune disorders is amazing news. Perhaps the future will bring even more incredible findings about the importance of vitamin D.

Title: New endometriosis prognosis study findings reported from Shanghai Jiao Tong University.
Date: October 1, 2009 Publication: Women’s Health Weekly
HighBeam Research

Fresh data on endometriosis are presented in the report ‘Epigenetics of endometriosis.’
According to recent research published in the journal Molecular Human Reproduction, “Endometriosis is a common gynecologic disorder with an enigmatic etiopathogenesis. Although it has been proposed that endometriosis is a hormonal disease, an autoimmune disease, a genetic disease, and a disease caused by exposure to environmental toxins, our understanding of its etiopathogenesis is still inadequate, as reflected by recent apparent setbacks in clinical trials on endometriosis.”

“In the last 5 years, evidence has emerged that endometriosis may be an epigenetic disease. In this article, the evidence in support of this hypothesis is reviewed, and its diagnostic, therapeutic and prognostic implications discussed.

Publications, up to the end of June 2009, pertaining to epigenetic aberration in endometriosis were identified through PubMed. In addition, publications on related studies were also retrieved and reviewed. Epigenetics appears to be a common denominator for hormonal and immunological aberrations in endometriosis. Epigenetics also appears to have a better explanatory power than genetics.

There is accumulating evidence that various epigenetic aberrations exist in endometriosis. In vitro studies show that histone deacetylase inhibitors may be promising therapeutics for treating endometriosis,” wrote S.W Guo and colleagues, Shanghai Jiao Tong University (see also Endometriosis Prognosis).

The researchers concluded: “Several lines of evidence suggest that epigenetics plays a definite role in the pathogenesis and pathophysiology of endometriosis. As such, endometriosis is possibly treatable by rectifying epigenetic aberrations through pharmacological means. DNA methylation markers may also be useful for diagnostic and prognostic purposes. It is also possible that the delineation of the epigenetic changes accompanied by the genesis and progression of endometriosis could lead to interventions that reduce the risk of developing endometriosis.”

Guo and colleagues published their study in Molecular Human Reproduction (Epigenetics of endometriosis. Molecular Human Reproduction, 2009;15(10):587-607).
http://www.ncbi.nlm.nih.gov/pubmed/19651637

For additional information, contact S.W. Guo, Institute of Obstetric and Gynecologic Research and Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China.

The publisher’s contact information for the journal Molecular Human Reproduction is: Oxford University Press, Great Clarendon St., Oxford OX2 6DP, England.

Keywords: People’s Republic of China, Shanghai, Endometriosis Prognosis, Adolescent Medicine, Autoimmune Disease, Autoimmune Disorder, Clinical Trial Research, Diagnostics, Endometriosis, Genetic Diseases, Genetics, Gynecologic Disorders, Gynecology, Immunology, Therapy, Treatment.
This article was prepared by Women’s Health Weekly editors from staff and other reports. Copyright 2009, Women’s Health Weekly via NewsRx.com.

Harvard Study Examines Endometriosis Cases After Menopause
Original story at vitabeat.com. Original press release at Harvard Health Publications.
January 31, 2006

Endometriosis, a gynecological disorder that affects as many as 1 in 10 women. With symptoms being the most severe during the reproductive years don’t necessarily disappear once a woman stops menstruating, according to a Harvard Study.

Endometriosis with symptoms including menstrual cramps, gastrointestinal problems, and pain during sex occurs when tissue similar to the lining of the uterus shows up on the walls of the abdominal cavity and the outer surfaces of the uterus, ovaries, fallopian tubes, bowel, bladder, and nearby organs.

But rather than exiting through the vagina, the way menstrual fluid does, it remains trapped, triggering inflammation and scar tissue.

But even after periods have ceased, the ovaries continue to produce small amounts of the hormone, so endometriosis may continue to cause trouble.

Dr. Martha K. Richardson says, “I think of endometriosis as a chronic disease that often — but not always — improves after natural or surgical menopause.”

Women with endometriosis also have a higher-than-average risk of autoimmune disorders and related problems, such as chronic fatigue syndrome, hypothyroidism, and fibromyalgia. They’re also more likely to develop ovarian cancer.

Scientists Discover Trigger for Autoimmune Diseases
Monday, December 22, 2008; 12:00 AM

MONDAY, Dec. 22 (HealthDay News) — Healthy adults have potential autoimmune disease-causing cells, but these cells stay in an “off” state, a U.S. study shows.

Immune cells that attack the body cause autoimmune diseases such as lupus and rheumatoid arthritis (RA). Whether the switched-off cells in healthy adults are true precursors of the self-attacking immune cells and, if so, what prevents them from causing disease in certain people, isn’t known, the researchers said.

J. Andrew Duty, of the Oklahoma Medical Research Foundation, and colleagues found that anergic (dormant) autoimmune disease-causing cells account for 2.5 percent of immune B-cells circulating in the blood of healthy adults.

These anergic cells don’t appear to cause problems in healthy adults, but did produce self-reactive antibodies when exposed to a strong stimulus in lab experiments. This means these anergic cells may contain the precursors for the self-attacking B-cells in patients with autoimmune disease, the researchers said.

In previously healthy people, anergy may somehow break down and allow self-attacking B-cells to cause autoimmune disease.

The study was published in the Dec. 22 online issue of The Journal of Experimental Medicine:

Learning To Tolerate Ourselves
Amy Maxmen
Published online December 22, 2008

Duty et al. find self-reactive B cells in healthy adults that might harm their own body if given the chance.

Checkpoints during B cell development ensure that immune cells won’t confuse the self for an intruder. At birth, many B cells express self-reactive receptors. Most of these potentially harmful cells are either set straight by rearranging new receptors or are eliminated before leaving the bone marrow. Yet a minority manages to escape, slipping into the periphery as mature B cells with a propensity for self-attack.

In healthy mice, autoimmunity is avoided because most self-reactive escapees, which classically express high levels of IgD and reduced IgM, are arrested in an anergic state. But until now, a similar population of anergic, autoreactive B cells hadn’t been found in humans.

Duty et al. have now spotted these cells in the blood of healthy adults, where they accounted for 2.5% of peripheral B cells. These cells turned out to be mature and autoreactive, bearing no signs of antigen encounter in vivo. The cells were also anergic, as they had faulty signaling in response to BCR ligation. These defects were overcome, however, when the authors gave cells a strong enough signal.

Autoreactive B cells are common in patients with autoimmune diseases, such as lupus or rheumatoid arthritis (RA). And the authors suspect that the new population may contain the precursors of these troublemaking cells. Lapses in early steps of self-tolerance have been shown to contribute to disease in patients with lupus or RA. Alternatively, suggests author Patrick Wilson, anergy may fail in these patients, allowing self-sabotaging cells to run free.

Why the body silences these potentially mutinous cells after they escape rather than putting them to death is unclear. Perhaps, suggests Wilson, a limited amount of autoimmunity isn’t such a bad thing, as long as it’s not chronic. For example, anergic cells might help attack pathogens disguised as self-antigens.

There are ongoing studies to make public the FACT that Endometriosis is an autoimmune disease.

September 26, 2002
A research team from the Endometriosis Association in Milwaukee; the National Institute of Child Health and Human Development, Bethesda Maryland; and the School of Public Health and Health Services at George Washington University in Washington D.C. carried out and analyzed a survey of 3,680 members of the Endometriosis Association who had endometriosis…”These findings suggest a strong association between endometriosis and autoimmune disorders,” said lead investigator Ninet Sinaii from the National Institute of Child Health and Human Development. “Health care professionals may need to consider these disorders when evaluating their patients for endometriosis.” – Read the entire article at the Endometriosis Association website, and the full text of the research at the Oxford Journal’s Human Reproduction website.

And then this year, Confirmation:

Autoimmune Endometriosis: Autoimmune Nature Confirmed
Elaine Moore
Sep 18, 2008

In 1984, researchers at the Upstate Medical Center in Syracuse, New York first suspected the autoimmune nature of endometriosis. Confirmation came in 2008.

Endometriosis is a disorder in which tissue normally found inside the uterus begins to grow elsewhere in the body. Endometriosis affects 10-20% of women of reproductive age and is associated with pelvic pain and infertility,

In 1984, Syracuse researchers first noted various immune phenomena including changes in complement levels in women with infertility caused by endometriosis. However, without the advanced analytical methods available today, they were unable to demonstrate the presence of endometrial autoantibodies.

The Autoimmune Link

A large study published in Human Reproduction in 2002 confirmed these early reports. Specifically, women with endometriosis were found to be more than 100 times as likely to have chronic fatigue syndrome as women in the normal population. Hypothyroidism was seven times more common than seen in the normal population and fibromyalgia twice as common.

Women with endometriosis also had higher than expected rates of autoimmune inflammatory diseases including systemic lupus erythematosus, Sjögren’s syndrome, and rheumatoid arthritis, as well as multiple sclerosis. Allergies occurred in 61 percent of patients compared to the 18 percent seen in the normal population. Asthma occurred in 12 percent of the patients compared to the 5 percent seen in the normal population. Among the patients who had chronic fatigue syndrome or fibromyalgia, up to 88 percent had allergies.

Pain Dysregulation Syndromes

Because chronic fatigue syndrome and fibromyalgia are considered to be associated with dysregulation of pain, the researchers proposed that endometriosis might also be associated with abnormal sensitivity to pain. Symptoms that may precede the development of endometriosis include fever, headaches, stiffness and joint problems. Other research recently found that a woman has more than five times the normal risk of getting endometriosis if she has a sister with the disease.

Autoimmune Nature

In 2007, researchers at National Jewish Hospital in Denver discovered that endometriosis lesions are characterized by the presence of abundant plasma cells, many of which produce IgM, and macrophages that produce BLyS/BAFF/TNFSF13B, a member of the TNF superfamily implicated in other autoimmune diseases. In addition, B lymphocyte stimulator (BLyS) protein was found to be elevated in the serum of endometriosis patients. These observations suggest that endometriosis occurs when BLyS-responsive plasma cells interact with retrograde menstrual tissues to give rise to endometriosis lesions.

Endometrial Autoantibodies

In June 2008, researchers at the Indian Council of Medical Research found the presence of antibodies to endometrial stroma in 60 percent of patients with endometriosis. Researchers propose that these anti-endometrial antibodies might be partially responsible for failure of implantation leading to infertility.

The observations made by researchers at National Jewish Hospital along with the demonstration of endometrial antibodies in patients with endometriosis confirm the autoimmune nature of endometriosis.

Resources:

Ninet Sinaii, S. Cleary, M. Ballweg, L. Nieman, and P. Stratton, “High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis” Hum Reprod. 2002;17(10):2715-2724

Gajbhiye R, Suryawanshi A, Khan S, Meherji P, Warty N, Raut V, Chehna N, Khole V, “Multiple endometrial antigens are targeted in autoimmune endometriosis,” Reproductive Medicine Online. 2008 Jun;16(6):817-24.

Aniko Hever, R. Roth, P. Hervezi, M. Marin, “Human endometriosis is associated with plasma cells and overexpression of B lymphocyte stimulator,” PNAS July 24, 2007 vol. 104 no. 30 12451-12456.

As you can see, the second article I posted contains a lot of tech speak. The next step is getting more researchers and media PR on this to get it in to the news in a more understandable manner.