This is a case study I wrote based on a real patient I met during my internship at the hospital this summer. I wanted to share it with you all and hopefully get some feedback. Do you think I accurately represented the science here? Let me know what you think!
As a disclaimer, I am an RD student so I need to stick to some level of conventional perspective. Also, I have references but I was unable to copy and paste the numbers into the paragraphs since I used endnotes. So I listed the references at the end but they’re not linked to the text the way they should be. Sorry!
The primary diagnosis of the patient (MG) outlined in this case study was vitamin B12 deficiency, a condition that is more widespread in the population than has been previously assumed. B12 is involved in the proliferation, maturation, and regeneration of neural cells. In combination with folate, vitamin B12 helps to maintain low homocysteine levels as an enzymatic essential cofactor. It binds to R-proteins and then intrinsic factor in the stomach, and is absorbed through the terminal ileal enterocytes. Excess B12 is thought to be stored in the liver. Vitamin B12 is important for DNA synthesis, and formation and maintenance of myelin sheaths, the synthesis of neurotransmitters, and erythropoiesis.
Vitamin B12 deficiency is associated with hematologic, neurologic, and psychiatric symptoms, such as megaloblastic anemia, paresthesias, peripheral neuropathy, irritability, personality change, memory impairment, dementia, depression, psychosis; deficiency also increases the risk of myocardial infarction and stroke. Like other causes of anemia, symptoms related to decreased oxygen-carrying capacity of the blood include tiredness and shortness of breath. Vitamin B12 deficiency also interferes with the function of the nervous system, and symptoms due to nervous system damage may occur even before the anemia is diagnosed. These conditions can become irreversible if B12 deficiency is not detected and treated early enough. The typical treatment for B12 deficiency is intramuscular injections, though supplemental B12 is effective in patients with adequate intrinsic factor and stomach acid to absorb the B12 through the intestine. Historically, dietary treatment consisted of frequent consumption of liver, a highly vitamin B12 rich food that also contains iron and folate, all nutrients important for the resolution of most types of anemia.
There are several patient populations at higher risk for B12 deficiency. Patients with an increased vitamin requirement include pregnant and breastfeeding women, patients with autoimmune disorders, or persons with HIV infection. Patients who regularly take proton pump inhibitors can also develop vitamin B12 deficiency, as PPIs inhibit the release of stomach acid which is necessary to uncouple the vitamin from protein in food. Vegetarians and vegans are at higher risk, as animal products are the main food sources of B12. Functional B12 deficiency is common in old age and has been diagnosed in 10% to 30% of patients older than 65 years of age. In older adults, B12 deficiency is typically attributed to reduced stomach acid, malabsorption, and/or pernicious anemia. Also, the incidence of H. pylori is high in elderly people and can lead to atrophic gastritis, leading to B12 malabsorption from disrupted production of stomach acid. B12 deficiency is also widespread in patients with renal disorders.
Pernicious anemia or atrophic gastritis is an autoimmune disorder where the parietal cells of the stomach are destroyed by autoimmune antibodies, preventing the production of intrinsic factor which is required for adequate absorption of B12 from food. Not surprisingly, pernicious anemia is commonly associated with other autoimmune diseases, particularly thyroiditis. Autoimmune diseases are found in an increased incidence among those with pernicious anemia, and include type 1 diabetes, vitiligo, and Addison disease. Pernicious anemia is the most common cause of vitamin B12 deficiency in younger adults who consume animal products regularly.
The patient in this case study has a past medical history consisting of two conditions that are commonly related to autoimmune processes: hypothyroidism and Cushing’s syndrome. In fact, approximately 90% of adult hypothyroidism cases are autoimmune in origin, mostly due to Hashimoto’s disease. In addition, patients with endogenous Cushing’s syndrome exhibit a high prevalence of primary thyroid disease, suggesting these diseases are commonly seen together. Further, patients with autoimmune thyroid disease have a high prevalence of B12 deficiency and particularly of pernicious anemia. Therefore, it is reasonable to suspect that this patient’s three major diagnoses – B12 deficiency, hypothyroidism, and Cushing’s syndrome – may all have a common autoimmune origin.
The patient, MG, is a 53 year old woman of Hispanic ethnicity brought into the Emergency Room by her daughter, complaining of left leg numbness and weakness. The patient reports that she had been having nausea for two days but otherwise was in good health. The daughter brought the patient in to rule out the possibility of stroke. Her past medical history includes hypothyroidism, Cushing syndrome, hypertension, cerebrovascular accident, and anxiety. Her CVA episode occurred 6 years ago on the right side, but symptoms have since resolved. She has had a hysterectomy. She takes three medications at home: atenolol, a beta blocker for chest pain, levothyroxine, a synthetic form of the thyroid hormone thyroxine for hypothyroidism, and atorvastatin, a cholesterol-lowering statin known by the trade name Lipitor. The patient does not use any tobacco, alcohol, or illegal drugs. Her native language is Spanish, but she speaks some English. She is allergic to penicillin but has no known food allergies. She works full-time as a housecleaner during the day. She was found to be anxious in the waiting room of the ER.
Pertinent positives on admission include shortness of breath, numbness of the left leg, and anxiety. The patient was hemodynamically stable, with no pallor, icterus, or edema. Heart sounds were normal, lungs were clear, and the patient was alert, awake, and oriented to time, place, and person. She had questionable right ptosis (eyelid drooping). A CT scan with contrast did not show acute bleed or infarct. The patient was negative for chest pain, fever, dizziness, headache, or loss of consciousness.
The patient is 5’0” and 213 pounds, with a BMI of 41.89, classifying her as Class III Obese, also called morbid obesity. On admission, the patient’s nutrition-related labs were as follows: H/H = 14.1/42.4, MCV = 87.2, Na/K = 137/3.9, Fasting glucose = 161 (H), BUN/Creatinine = 16/0.74, Ca = 9.8, Phos = 2.3 (L), Albumin = 4.0, AlkPhos = 82, AST/ALT = 15/15, Mg = 1.8, Total Cholesterol = 239 (H), HDL = 33, LDL = 150 (H), Triglycerides = 274 (H), Vitamin B12 = 282, Homocysteine = 7.0, TSH = 1.506, HbA1c = 6.2 (H).
A few of her abnormal nutrition-related labs and physical findings may also be related to her past medical history and current conditions. Obesity is significantly more common in both patients with hypothyroidism and Cushing’s syndrome. Clinical hypothyroidism is frequently associated with weight gain, decreased thermogenesis, and lower metabolic rate, and clinical evidence suggests that thyroid dysfunction is linked to significant changes in body weight and may be a risk factor for overweight and obesity. In addition, obesity is a frequent clinical sign of Cushing’s syndrome, typically manifesting as central adiposity.
Hypertension is directly related to both hypothyroidism and Cushing’s syndrome. Diastolic hypertension is often present in hypothyroidism, due to increased peripheral vascular resistance and low cardiac output. In addition, hypertension is a major and frequent comorbidity of Cushing’s syndrome, with a prevalence of approximately 80% in adults. Several mechanisms may explain the impact of hypercortisolemia on hypertension, including the mineralocorticoid effects of cortisol, the activation of the renin angiotensin system (RAS); and the action of cortisol on peripheral and systemic vasculature. Thus, while hypertension can frequently be nutrition related, it is more likely that this patient’s hypertension is a comorbidity of her chronic diseases.
High cholesterol, particularly high LDL cholesterol, and high triglycerides is more common in patients with hypothyroidism, especially in hypothyroid obese patients. This may be because thyroid hormone stimulates LDL receptor activity, increasing LDL clearance and catabolism, as well as increasing secretion of cholesterol into the bile. In Cushing’s syndrome, there typically is an increase of triglyceride and total cholesterol levels, and hypercortisolemia shares many features with metabolic syndrome including insulin resistance, abnormal fasting glucose levels, hypertension, obesity, and dyslipidemia. These effects may be due to direct and indirect cortisol action on lipolysis, free fatty acid production and turnover, VLDL lipoprotein synthesis, and fat accumulation in the liver.
Elevated fasting blood glucose, and even frank type 2 diabetes, is a frequent finding in Cushing’s syndrome. This is likely due to the insulin-resistance caused by high levels of cortisol in the blood. Cortisol also stimulates hepatic gluconeogenesis, and regulates the production and metabolism of glucose in the body. This glucocorticoid effect on blood sugar control and insulin sensitivity could possibly explain this patient’s high fasting glucose, high HbA1c, and even possibly her elevated triglycerides. The patient is taking levothyroxine, which is a synthetic thyroid hormone that supplies only T4, the precursor to the metabolically active thyroid hormone T3. When taken correctly, levothyroxine reduces or reverses the symptoms of hypothyroidism. The patient is not being treated for Cushing’s syndrome, which typically requires either surgical intervention or pharmaceutical treatment using glucocorticoid synthesis inhibitors, dopamine agonists, and/or serotonin antagonists.
Some novel approaches exist, such as treatment with PPAR-gamma ligands or retinoic acid, which may help inhibit ACTH production or tumor growth. Medications to control excessive production of cortisol include ketoconazole (Nizoral), mitotane (Lysodren) and metyrapone (Metopirone). Sometimes surgical removal of the adrenal glands (bilateral adrenalectomy) is used in more extreme cases of Cushing’s syndrome. This patient does not appear to have had any allopathic or surgical treatment of her Cushing’s syndrome according to the medical records.
The patient reported that she had been attempting to follow a self-described ‘healthy’ diet, including avoiding sugar, soda, and junk foods, eating lower fat foods and fresh fruits and vegetables, engaging in portion control, and reducing sodium and omitting salt when cooking. She eats some type of animal protein every day. One issue that came up during discussion with the patient is that she frequently skips breakfast, as she is very busy during the day and does not make time for eating in the morning. She also does not eat any snacks during the day, and sometimes only eats one meal on days when she is especially busy. She assumed that skipping meals might also help her lose weight; a belief unfounded in the scientific literature.
The patient is 5 feet tall, weighs 213 pounds, and the HAMWI ideal body weight method estimates her ideal weight as 100 pounds. Because the patient has a BMI of 41.89, and is at 213% of her ideal body weight, an adjusted body weight was used to calculate her nutrient needs. To adjust her body weight, 25% of the difference between her current and ideal body weight was added to her ideal body weight, giving a total adjusted body weight of 58 kilograms. Her needs were calculated using the following estimated needs: 25-30 kcal/kg, 0.8-1.0 g/kg protein, and 30 mL/kg fluid. Her needs were estimated to be: 1450-1740 kcal, 46-58 g protein, and 1740 mL fluid. After speaking with the patient about her diet, it was established that her major nutrition-related problem was an inappropriate meal and snack pattern related to a food and nutrition knowledge deficit as evidenced by the patient’s reported diet history.
The patient’s initial diet order was a “Cardiac Diet”, which restricts sodium to less than 2400 mg, saturated fat to less than 10% of calories, and cholesterol to less than 300 mg per day. This diet is appropriate per the patient’s altered lab values, including elevated cholesterol and high blood pressure. While these symptoms are typically associated with both hypothyroidism and Cushing’s syndrome, the cardiac diet restrictions may possibly reduce the severity of these symptoms. It may have been warranted to place the patient on a 1600 calorie diabetic diet restriction, which would have controlled the number of carbohydrate foods she was able to order while in the hospital. While the patient does not have diabetes, Cushing’s syndrome is associated with hyperglycemia, and a carbohydrate controlled diet may have been helpful for reducing her blood sugar. However, a diabetic diet restriction is not necessarily used for non-diabetic patients with high blood sugar, and thus the initial diet order was not restricted in this way.
The major nutritional care plan for this patient involved educating her on weight loss strategies, as well as providing a list of foods rich in vitamin B12 in order to help avoid future deficiencies. The etiology of the B12 deficiency for this patient is currently unknown; if the issue is reduced absorption due to autoimmune gastritis or pernicious anemia, it is unlikely that including B12-rich foods will make a difference in her risk of future deficiency. However, if the deficiency was due to inadequate intake, the purposeful inclusion of B12-rich foods will help the patient avoid deficiency. Weight loss is an important goal for this patient as well, as she is significantly overweight (213% of IBW), putting her at risk for other chronic diseases in the future. Losing weight can be challenging for patients with hypothyroidism and/or Cushing’s syndrome; however, strategies for weight loss were discussed with the patient in order to facilitate her future weight loss attempts.
The patient was given a printed handout describing science-based weight loss strategies and providing a list of vitamin B12-rich foods. Weight loss strategies discussed with the patient included: implementing a regular meal pattern with reduced overall calories, eating meals and snacks balanced with all three macronutrients, prioritizing adequate sleep, taking 30 minute walks after dinner, drinking enough water during the day, and avoiding processed foods if possible. Foods rich in vitamin B12 were recommended as well, including fish and shellfish, liver, beef, lamb, dairy, eggs, and other animal foods. The patient was discharged later that day, so there was no opportunity to further manage her nutritional needs.
Though the patient was not at the hospital long enough to assess medical management of this nutritional care plan, her attitudinal change at the end of the education session suggested that she was intending to implement some of the changes we discussed upon discharge from the hospital. Some of her incorrect beliefs about effective weight loss strategies were addressed, so it can be expected that she will make an effort to change her behavior to better support her weight loss regimen. She expressed an intention to be mindful about her vitamin B12 intake and include the foods listed on the handout she was provided. If a follow-up appointment were possible with this patient, it would be important to assess changes in weight, cholesterol levels, blood sugar control, and serum vitamin B12 levels. If the intervention were effective, we would expect to see a reduction in BMI, cholesterol levels below 200 mg/dL, an HbA1c below 5.7%, and serum B12 levels closer to 911 pg/mL. After the patient received intramuscular vitamin B12 injections, her symptom of left leg numbness and weakness was resolved during her admission.
The nutritional care plan for this patient was quite basic, as there was little time to go through her complete nutritional history, including personal habits and prior weight loss attempts. However, the patient was provided with pertinent information for weight loss and increasing vitamin B12 intake; both of these were important diet-related issues for this patient. Had the patient stayed at the hospital longer, it would have been possible to monitor any changes in lab values, particularly blood sugar levels, as these fluctuate more directly with dietary changes than other measures that would be important to monitor in this patient.
Were it possible to follow this patient in an outpatient setting, the nutritional care plan may have differed. It would have been helpful to evaluate the etiology of this patient’s B12 deficiency by testing her for intrinsic factor antibodies and parietal cell antibodies. If the patient tested positive for these antibodies, there would be several nutritional changes that could be recommended to help reduce her autoimmune related symptoms; especially considering that her past medical history includes other conditions that are possibly autoimmune related.
While there are no specific nutritional guidelines for autoimmune disease provided by the Academy of Nutrition and Dietetics, several theories have emerged for the dietary management of autoimmune symptoms and severity. Certain dietary antigens, such as gluten, milk proteins, lectins, and soy protein have been proposed as potential triggers for autoimmune diseases such as celiac disease, multiple sclerosis, type 1 diabetes, and rheumatoid arthritis. Cereal grains in general have been linked to intestinal permeability and inflammation, two factors that are thought to contribute to the development of autoimmune disease. Inflammation may be a key factor in the exacerbation of autoimmune symptoms, and dietary factors associated with inflammation include a shift towards a higher n-6:n-3 fatty acid ratio and a high intake of simple sugars. In addition, it is possible that autoimmune disease is linked to changes in the gut microbiota, an issue that may be managed using probiotic and/or prebiotic foods to support healthy gut bacteria.
Vitamin A could be a useful therapeutic tool for this patient for a variety of reasons. Vitamin A has been shown to prevent experimental Cushing’s syndrome in mice, and the authors of this research suggest that vitamin A could potentially reverse the endocrine alterations and symptoms observed in Cushing’s syndrome. It is theorized that vitamin A supplementation might reduce the risk of subclinical hypothyroidism due to its effects on TSH levels. In addition, vitamin A deficiency is associated with impaired immunity, and may be an important nutrient in the treatment of autoimmune disease. Vitamin A deficiency has even been linked to diseases such as rheumatoid arthritis, lupus and type I diabetes, so it is possible that vitamin A plays a role in the pathogenesis of autoimmune conditions. However, vitamin A is a potentially toxic nutrient, and must be used carefully when used as a therapeutic supplement.
Though these theories have yet to be demonstrated to be effective in a variety of clinical studies, for this patient, it may be worth shifting her diet towards one that is anti-inflammatory with a reduction in the anti-nutrients and pro-inflammatory factors common in a Western diet. Therefore, were this patient to be counseled in an out-patient setting, it may be beneficial to her to recommend a diet high in omega-3 fatty acids, low in potentially autoimmune-provoking proteins from foods like dairy, soy, cereal grains, and legumes, and supplemented with prebiotic and probiotic foods to support gut health and a beneficial diversity of microflora. While these dietary changes are not specifically recommended as standard guidelines for the treatment of autoimmune disease, there is potential for a reduction in symptoms when consuming a more immune-supporting diet and avoiding foods that may provoke an inflammatory or immune response. Unfortunately, there are no established guidelines to treat the autoimmune patient using dietary manipulation or nutrient supplementation.
This case study demonstrates the need for the expansion of research on topics of rheumatology and autoimmunity, and touches on the potential for dietary manipulation to change the course of autoimmune disease progression or development. While this patient has not been diagnosed with an autoimmune disease, her cluster of frequently autoimmune-related disorders suggests that there could potentially be a common etiology to her B12 deficiency, hypothyroidism, and Cushing’s syndrome. It would be worth further testing to establish if this patient has any autoantibodies that could be the root cause of her medical conditions, and if so, making these dietary changes could positively impact the course of her health. As in several other cases observed during this rotation, longer term follow-up with this patient could have proved very helpful in the reduction of her symptoms and achievement of weight loss.
1. Herrmann W, Obeid R. Causes and early diagnosis of vitamin B12 deficiency. Dtsch Arztebl Int. 2008 Oct;105(40):680-5. doi: 10.3238/arztebl.2008.0680. Epub 2008 Oct 3. PubMed PMID: 19623286; PubMed Central PMCID: PMC2696961.
2 Herrmann W, Obeid R. Causes and early diagnosis of vitamin B12 deficiency. Dtsch Arztebl Int. 2008 Oct;105(40):680-5. doi: 10.3238/arztebl.2008.0680. Epub 2008 Oct 3. PubMed PMID: 19623286; PubMed Central PMCID: PMC2696961.
3 Herrmann W, Obeid R. Causes and early diagnosis of vitamin B12 deficiency. Dtsch Arztebl Int. 2008 Oct;105(40):680-5. doi: 10.3238/arztebl.2008.0680. Epub 2008 Oct 3. PubMed PMID: 19623286; PubMed Central PMCID: PMC2696961.
4 Oh R, Brown DL. Vitamin B12 deficiency. Am Fam Physician. 2003 Mar 1;67(5):979-86. Review. PubMed PMID: 12643357.
5 Herrmann W, Obeid R. Causes and early diagnosis of vitamin B12 deficiency. Dtsch Arztebl Int. 2008 Oct;105(40):680-5. doi: 10.3238/arztebl.2008.0680. Epub 2008 Oct 3. PubMed PMID: 19623286; PubMed Central PMCID: PMC2696961.
6 Luzina EV, Lareva NV. [Anemia and gastrointestinal tract diseases]. Ter Arkh. 2013;85(4):102-5. Review. Russian.
7 Neumann WL, Coss E, Rugge M, Genta RM. Autoimmune atrophic gastritis-pathogenesis, pathology and management. Nat Rev Gastroenterol Hepatol. 2013 Jun 18. doi: 10.1038/nrgastro.2013.101. [Epub ahead of print] PubMed PMID: 23774773.
8 Carstensen H, Krabbe S, Wulffraat NM, Nielsen MD, Ralfkiaer E, Drexhage HA. Autoimmune involvement in Cushing syndrome due to primary adrenocortical nodular dysplasia. Eur J Pediatr. 1989 Nov;149(2):84-7. PubMed PMID: 2591414.
9 Amino N. Autoimmunity and hypothyroidism. Baillieres Clin Endocrinol Metab.1988 Aug;2(3):591-617. Review. PubMed PMID: 3066320.
10 Niepomniszcze H, Pitoia F, Katz SB, Chervin R, Bruno OD. Primary thyroid disorders in endogenous Cushing’s syndrome. Eur J Endocrinol. 2002 Sep;147(3):305-11. PubMed PMID: 12213667.
11 Ness-Abramof R, Nabriski DA, Braverman LE, Shilo L, Weiss E, Reshef T, Shapiro MS, Shenkman L. Prevalence and evaluation of B12 deficiency in patients with autoimmune thyroid disease. Am J Med Sci. 2006 Sep;332(3):119-22. PubMed PMID: 16969140.
12 Biondi B. Thyroid and obesity: an intriguing relationship. J Clin Endocrinol Metab. 2010 Aug;95(8):3614-7. doi: 10.1210/jc.2010-1245. PubMed PMID: 20685890.
13 Tiryakioglu O, Ugurlu S, Yalin S, Yirmibescik S, Caglar E, Yetkin DO, Kadioglu P. Screening for Cushing’s syndrome in obese patients. Clinics (Sao Paulo). 2010;65(1):9-13. doi: 10.1590/S1807-59322010000100003. PubMed PMID: 20126340; PubMed Central PMCID: PMC2815288.
14 Stabouli S, Papakatsika S, Kotsis V. Hypothyroidism and hypertension. Expert Rev Cardiovasc Ther. 2010 Nov;8(11):1559-65. doi: 10.1586/erc.10.141. Review. PubMed PMID: 21090931.
15 Singh Y, Kotwal N, Menon AS. Endocrine hypertension – Cushing’s syndrome. Indian J Endocrinol Metab. 2011 Oct;15 Suppl 4:S313-6. doi: 10.4103/2230-8210.86973. PubMed PMID: 22145133; PubMed Central PMCID: PMC3230089.
16 Fraser R, Davies DL, Connell JM. Hormones and hypertension. Clin Endocrinol. 1989;31:701–46.
17 Abrams JJ, Grundy SM. Cholesterol metabolism in hypothyroidism and hyperthyroidism in man. J Lipid Res. 1981 Feb;22(2):323-38. PubMed PMID: 7240961.
18 Friedman, M, Byers, SO, Rosenman, RH. Changes in excretion of intestinal cholesterol and sterol digitonides in hyper- and hypothyroidism. Circulation 1952; 5:657.
19 Arnaldi G, Scandali VM, Trementino L, Cardinaletti M, Appolloni G, Boscaro M. Pathophysiology of dyslipidemia in Cushing’s syndrome. Neuroendocrinology. 2010;92 Suppl 1:86-90. doi: 10.1159/000314213. Epub 2010 Sep 10. Review. PubMed PMID: 20829625.
20 Nosadini R, Del Prato S, Tiengo A, Valerio A, Muggeo M, Opocher G, Mantero F, Duner E, Marescotti C, Mollo F, Belloni F. Insulin resistance in Cushing’s syndrome. J Clin Endocrinol Metab. 1983 Sep;57(3):529-36. PubMed PMID: 6348064.
21 Gorman LS. The adrenal gland: common disease states and suspected new applications. Clin Lab Sci. 2013 Spring;26(2):118-25. PubMed PMID: 23772480.
22 MedlinePlus. Bethesda (MD): National Library of Medicine (US). Levothyroxine. Available from: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682461.html. Accessed 6/30/13.
23 Labeur M, Theodoropoulou M, Sievers C, Paez-Pereda M, Castillo V, Arzt E, Stalla GK. New aspects in the diagnosis and treatment of Cushing disease. Front Horm Res. 2006;35:169-78. Review. PubMed PMID: 16809932.
24 Bellisle, F. (2008). Impact of the daily meal pattern on energy balance. Food & Nutrition Research, 48(3), 114-118.
25 Hamwi GJ. Therapy: changing dietary concepts. In: Danowski TS, ed. Diabetes Mellitus: Diagnosis and Treatment. American Diabetes Association, 1964.
26 National Institutes of Health. Nutrition for Patients with Cushing Syndrome. Patient Information Publications, 1997.
27 Denham JM, Hill ID. Celiac Disease and Autoimmunity: Review and Controversies. Curr Allergy Asthma Rep. 2013 May 17. [Epub ahead of print] PubMed PMID: 23681421.
28 Armstrong D, Don-Wauchope AC, Verdu EF. Testing for gluten-related disorders in clinical practice: the role of serology in managing the spectrum of gluten sensitivity. Can J Gastroenterol. 2011;25(4):193-197.
29 Zhao JH, Sun SJ, Horiguchi H, Arao Y, Kanamori N, Kikuchi A, Oguma E, Kayama F. A soy diet accelerates renal damage in autoimmune MRL/Mp-lpr/lpr mice. Int Immunopharmacol. 2005 Oct;5(11):1601-10. PubMed PMID: 16039550.
30 Hvatum M, Kanerud L, Hällgren R, Brandtzaeg P. The gut-joint axis: cross reactive food antibodies in rheumatoid arthritis. Gut. 2006 Sep;55(9):1240-7. Epub 2006 Feb 16. PubMed PMID: 16484508; PubMed Central PMCID: PMC1860040.
31 Monetini L, Cavallo MG, Manfrini S, Stefanini L, Picarelli A, Di Tola M, Petrone A, Bianchi M, La Presa M, Di Giulio C, Baroni MG, Thorpe R, Walker BK, Pozzilli P; IMDIAB Group. Antibodies to bovine beta-casein in diabetes and other autoimmune diseases. Horm Metab Res. 2002 Aug;34(8):455-9. PubMed PMID: 12198602.
32 de Punder K, Pruimboom L. The dietary intake of wheat and other cereal grains and their role in inflammation. Nutrients. 2013 Mar 12;5(3):771-87. doi: 10.3390/nu5030771. PubMed PMID: 23482055.
33 Mathis, D. & Benoist, C. Microbiota and autoimmune disease: the hosted self. Cell Host Microbe 10, 297–301 (2011).
34 Páez-Pereda M, Kovalovsky D, Hopfner U, Theodoropoulou M, Pagotto U, Uhl E, Losa M, Stalla J, Grübler Y, Missale C, Arzt E, Stalla GK. Retinoic acid prevents experimental Cushing syndrome. J Clin Invest. 2001 Oct;108(8):1123-31. PubMed PMID: 11602619; PubMed Central PMCID: PMC209498.
35 Farhangi MA, Keshavarz SA, Eshraghian M, Ostadrahimi A, Saboor-Yaraghi AA. The effect of vitamin A supplementation on thyroid function in premenopausal women. J Am Coll Nutr. 2012 Aug;31(4):268-74. PubMed PMID: 23378454.
36 Harbige LS. Nutrition and immunity with emphasis on infection and autoimmune disease. Nutr Health. 1996;10(4):285-312. Review. PubMed PMID: 8738870.
37 S. Manicassamy et al. TLR2-dependent induction of vitamin A metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits Th-17-mediated autoimmunity. Nature Medicine, March 2009
38 S. Manicassamy et al. TLR2-dependent induction of vitamin A metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits Th-17-mediated autoimmunity. Nature Medicine, March 2009