G4. Autoimmune Disease & Vitamin D

"What does stress have to do with autoimmune disease? or vitamin D?

You want me to take a bath?

Are you kidding me?"

Answer: "No."

The body needs vitamin D and magnesium in order to protect against allergic sensitivity within the immune system. Some types of immune cells can be made to be more or less “tolerant” of foreign protein - such as the DNA of an expectant infant, which is “foreign” to its mother’s DNA. The baby has half the DNA from the father too.     

     Some conditions, such as chronic stress, can make it difficult for the intestines to absorb magnesium which include having an excess amount of vitamin D. Excess vitamin D can lead to an over absorption of calcium in the intestines and an increased retention of the mineral by the kidneys, while at the same time less magnesium is absorbed and more is lost by the kidneys. A bath or foot soak with magnesium sulfate salt can bypass the intestinal problem of poor absorption and help provide what the kidneys need. Epsom salt is a well known brand of magnesium sulfate salt, about one cup to a half bath of water, soak for twenty minutes one to three times per week for better health and mood. It may help patients with autism or Bipolar Disorder Type 1 to have better mood stability. (G.1, G.2) Magnesium chloride is another form that can be used for topical skin absorption as concentrated drops or in a bath. (G.3)     

     The sulfate portion of the Epsom salt may be beneficial in addition to the magnesium for people with some types of conditions such as autism and may be more protective in a food environment that contains the herbicide glyphosate as a contaminant. It may interfere with the type of CYP enzyme (CYP enzymes are a large group important in many areas of the body: (G.4), more on this topic later) that is needed for the body to be able to use the sunshine method to make biologically active forms of vitamin D or of sulfate. The Epsom salt bath would provide the sulfate through skin absorption which would bypass the enzyme needed for the metabolic pathway that requires sunshine.

     Too much can be a health risk as well as too little, because magnesium is electrically active and can cause the heart rate to slow down. Adequate vitamin D for mothers-to-be can help protect baby and mom from allergic immune reactions which may increase risk of autoimmune disease later in life. Magnesium is also important during pregnancy and lactation. Adequate intake might help relieve muscle cramps, a common discomfort of pregnancy. Other symptoms might include constipation, irritable mood or headaches, and ringing in the ears can be a more severe symptom.

     CYP enzymes are involved in digestion and in the metabolism of many drugs including the opioids. If glyphosate is inhibiting the group then it may be part of the reason for the increased number of opioid overdose deaths. With less ability to breakdown the medication any dose that is consumed would remain in the body longer and might reach a deadly dose in a more petite woman or man. People with chronic kidney or liver disease are also at greater risk for inadequate breakdown of opioid and morphine drugs. (G.5) 

     Coffee lovers can rejoice, cafestol, a phytonutrient found in coffee helps promote the CYP enzyme involved in breaking down opioids. While grapefruit juice contains a phytochemical that can inhibit the enzyme:

•  “Administration of CYP3A4 substrates or inhibitors can increase opioid concentrations, thereby prolonging and intensifying analgesic effects and adverse opioid effects, such as respiratory depression. Administration of CYP3A4 inducers can reduce analgesic efficacy.10,11,16 In addition to drugs that interact with CYP3A4, bergamottin (found in grapefruit juice) is a strong inhibitor of CYP3A4,26 and cafestol (found in unfiltered coffee) is an inducer of the enzyme.27” (G.5)

Coffee in quantity, (> 6 cups/day), such as “a pot a day” has been associated with prenatal issues. However one or two small servings of a caffeinated beverage during pregnancy is likely to be safe. (G.28) The standard recommendation used to be “none” and so many people may be familiar with that advice, however research has found coffee and caffeine to be safer than was feared. I like to know and provide the upper and lower ranges of safety - the “too much” and the “probably okay for most people” range or tolerable limits. A small serving of grapefruit juice is likely safe for most people. It has been a well known “effective care” recommendation in dietetics for patients taking certain medications to avoid grapefruit juice or grapefruit. 

     Based on the article and the excerpt people with severe kidney or liver disease and who are taking opioid medications might be safer to avoid all use of grapefruit juice. (G.5) Coffee would not be advisable for someone with severe kidney disease though either.

     Checking for drug and nutrient interactions is part of a thorough nutrition assessment as negative symptoms may often be due to underlying problems that are being caused by something happening as part of the daily routine. A thorough nutrition assessment is like a detective investigating a mystery, looking for clues to what might be disrupting normal function. 

 t’s not well understood why, but women are much more at risk for autoimmune disease than men (G.6) and the reason may include an inadequate supply of vitamin D or a malfunction in the vitamin D metabolism. An active form of vitamin D helps protect against an autoimmune response occurring when the woman’s immune response has to cope with antigens during pregnancy. (G.7)    

     Without going into great detail, the vitamin D3 form is the more bioactive of the different types of supplemental vitamin D that are available and might help reduce risk for an inflammatory reaction (G.7) occurring that can lead to autoimmune antibodies being formed. The D3 form would be more likely to help protect against autoimmune risk for women who may be in childbearing years, and for their infants if they were to conceive, than the vitamin D2 form that is commonly used in multi-vitamins.     

     A half hour of sunshine during summer months with arms and face exposed several days a week is also a source of vitamin D and sunshine helps form bioactive sulfate for us at the same time. If regular exposure to sunshine isn’t possible then magnesium sulfate “Epsom salt” foot soaks or baths would provide bioactive sulfate and magnesium through skin absorption. Both are nutrients that are important for pregnancy and health in general in addition to vitamin D.

     Other sources of vitamin D include fortified milk and milk equivalents, other fortified dairy products and equivalents, fortified breakfast foods and meal bars, vitamin D2 or D3 may be used in fortified products and should be listed on the label. Salmon, tuna, sardines, egg yolks, and mushrooms are natural sources of vitamin D. (G.8)

     People who may be more at risk for vitamin D deficiency or difference in vitamin D metabolism include those with a dark skin complexion living in a cold climate with limited sun exposure; and those with a very, very fair skin complexion who tend to burn or freckle in the sunshine rather than tan - this may suggest something different than typical is happening in the vitamin D metabolism system and has been associated with autism risk. (G.9)

     Is it “Race/Color” or “Genetic” discrimination to discuss potential health concerns that may be more of a risk for some individuals or individualized nutrition education? 

     Since it is not related to a job situation with an applicant or employee then it seems like an Effective Care best practice in nutrition education to instruct on the increased need for dietary or supplemental sources of vitamin D for individuals with a dark skin complexion. It would be negligent of me as a nutrition counselor to not provide basic information that has been known for over a century. 

The autism and vitamin D3 connection is still in the area of educated guesses and hypotheses yet to be tested. The fair complexion/autism connection was made by a mother who has children with autism and who herself has autism.  (G.9)

     The issue of supplementation is clear for the person with a dark skin complexion in a cold climate - get adequate dietary sources of some form or another. For those with very fair complexions and who tend to freckle or sunburn the issue is more complex. Too much active vitamin D due to an inability to break down excess amounts may be involved with the cause of the symptom of sun sensitivity. Adequate vitamin D is important for everyone but too much supplementary or concentrated dietary sources of D such as cod liver oil might provide too much.

     My interest in vitamin D metabolism turns out to be due to a genetic difference that I found I have. I also tend to get sunburns and freckles and feel flu-like symptoms the day after spending a long time in the sun. My mother gave me a spoonful of cod liver oil daily for a while when I was a child with skin eczema - it didn't get better. I feel better when I avoid excess vitamin D and sunshine.  Disclosing personal genetic information of an individual other than yourself can be prohibited as “Genetic Discrimination” by the U.S. Equal Employment Opportunity Commission (EEOC) depending the situation. (6.10)

I am for pair-bonds or monogamy, I value the closeness, I just also value civil rights and diversity and think women shouldn’t be discriminated against for sexual choices or orientation. 

     From a health perspective the long term pair-bond may be better for both babies and for pregnant women because it may help the woman's body to be less likely to have an "allergic" antibody reaction to the DNA of her expected infant. (G.10)

     The health of the male may be involved as well, men can also produce antibodies against their own DNA. (G.11)

     Frequent exposure to the father-of-the-baby's DNA may help the woman's body to be less reactive against the foreign antigen - when she is well nourished. The active hormone form of vitamin D, the D-3 form, is involved.        And indeed, low vitamin D levels in males is associated with less success at impregnating a woman and that may have to do with there being more of the male DNA antibodies present but the study didn't check that lab test. The sperm in other physical ways were identical between the group of men with normal vitamin D and some consistent success at impregnating women and the group of men who had vitamin D levels below 30 ng/ml and less success at impregnating women than the group with levels of vitamin D above 30 ng/ml. (G.12)

     What we all are not supposed to talk about is that Monsanto's "Roundup" herbicide may be inhibiting the activation of Vitamin D to the D-3 form. We're also not supposed to talk about the history of the chemical company which is associated with WWII chemical companies that made chemicals used in warfare and in the concentration camp gas chambers. (G.13) Or that the company is being investigated for possibly colluding with a top EPA official to cover up evidence that glyphosate is carcinogenic. (G.14, G.15) 

     While we're all not talking about those issues, if you happen to be a man or a woman who is struggling with infertility issues, then you may need the active, natural form of D-3, cholecalciferol, (see the next paragraph), as a supplement, because the glyphosate may be inhibiting the sunshine method that our body uses to make and activate vitamin D and also a bioactive form of sulfate, it is also a sunshine nutrient. Soaking in Epsom salt would provide a bioactive source of sulfate that bypasses the CYP enzyme required for the sunshine method, if the enzyme is being inhibited by glyphosate. (G.16.11.53)
    To complicate a complicated story further, there are two forms of vitamin "D-3" and the natural form was found to be slightly better than the other for immune support in one study with renal allograft (transplant) patients. Better symptom control was seen with the natural cholecalciferol form of vitamin D-3 compared to the synthetic calcitriol form of vitamin D-3. (g.25) - On a supplement bottle it could legally say vitamin “D-3” for either form, I’m not sure [fact checker-STAT-the jargon may simply be a problem across different references and fields of study]. 

     Check for the specific word “cholecalciferol” on a food or supplement label or look for natural food products that are good sources. A list of “Top Sources of Vitamin D-3 (cholecalciferol)” includes both natural and fortified foods, I’m not sure if calcitriol might be an allowed substitute in the fortified foods that are listed: (G.17).

     To add more complication to the jargon, biologically speaking the “vitamin D” chemical is actually not an “essential nutrient” because we can make it with the help of sunshine during normal health. It is considered a secosteroid biologically speaking, and the active form is actually a very powerful hormone that acts in many systems of the body. It is not just a “vitamin” that helps make strong bones. Medications that might be similar to “hormone D-3” are the group of steroid drugs such as Prednisone. It also affects calcium absorption in the intestines in a way that is opposite of cholecalciferol (D-3), and can be used to help treat an accidental overdose, a problem seen with animals due to pet food fortification errors. Providing charcoal and withholding excess calcium and phosphorus in the diet is also recommended while treating an overdose of vitamin D-3. (G.18)

This information about vitamin D is not part of standard education about the nutrient - yet. The area of immunology during pregnancy and early implantation is advancing.

    The fetus plays a role in decreasing the activity of the maternal immune T cells. A decrease in the internal level of tryptophan within the maternal T cells seems to be involved. A diet containing large amounts of tryptophan was associated with more fetal loss than a standard diet in animal research. For ethical reasons this field of research takes place with lab animals or murine animals. (G.19)

• "And third, fetal survival depends on tolerogenic mechanisms
  that block maternal T cell responses." (G.19)

The estrogen level of the mother may affect the ability of the fetus to inhibit her immune T cells:

• "Estrogen treatment and pregnancy both induced FoxP3 protein expression to a similar degree both in vitro and in vivo, suggesting that high estrogen levels during pregnancy may help maintain fetal tolerance by promoting regulation (G.20.65). Trophoblast-derived chemokines have also been implicated (G.21.63)." (G.22)

It had previously been known that estrogen has protective effects against autoimmune disease. Symptoms for some types can improve for a woman during her pregnancy and then flair back up after delivery.

• "Estrogen has been shown to protect against the development of autoimmune disease, yet the mechanism is not known." (G.20.65)

The study found that estrogen treatment led to an increase in the FoxP3 protein in CD4+CD25− T cells. These are a type of regulatory T cell of the immune system which are essential for protecting against self intolerance - ie autoimmunity:

• "Recently, in a TCR-transgenic mouse model where full protection against spontaneous experimental autoimmune encephalomyelitis could be achieved by the transfer of wild-type CD4+CD25− T cells, Furtado et al. (G.23.47) showed that responsiveness to IL-2 was required for the suppressive function."  (G.24)

     Having walked this around a block or two, I'll get to the point, cholecalciferol, vitamin D3, helps the body make adequate supplies of Treg immune cells, and it is better at it than calcitriol. (G.25) Calcitriol is a synthetic form of vitamin D3 called "Rocaltrol", (G.26), I'm not sure of the exact difference chemically - but they both can help our body tell us who is friend and who is foe.

There seems to be a very, very strong biological urge in men to be the "only one" and it may be to help assure that his sperm will be the ones that succeed at impregnation and research does suggest that familiarity by the woman's body may help her ovum to recognize sperm with the familiar DNA and reject/kill off by apoptosis any sperm that try to enter the ovum with unfamiliar DNA. Natural fertilization is safest for the baby because in test tube fertilization the sperm is made to enter the cell by the technology instead of letting the ovum do whatever it would normally do  - which allows sperm DNA to enter but not sperm mitochondrial DNA, while the test tube fertilization allows the sperm mitochondrial DNA to enter the ovum making the babies genetically different than most other humans who only have maternal mitochondrial DNA. (G.27)