December 2, 2020

New review investigates the potential benefits of probiotics in metabolic disorders

According to a new study published last week in Nutrients, researchers investigated the potential benefits of probiotics in metabolic diseases including obesity, type 2 diabetes, hypertension, and dyslipidemia. Previous research has demonstrated the association of the gut microbiome with metabolic markers and type II diabetes.

In this study, researchers designed a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014. Probiotic consumption was considered when an individual reported eating yogurt or a probiotic supplement during the 24-hour recall or the Dietary Supplement Use 30-Day questionnaire. This study included 38,802 individuals and 13.1% reported consuming probiotics. As a result, the incidence of obesity and hypertension was lower in the probiotic group. Body mass index (BMI), systolic and diastolic pressure, and triglycerides were all lower and HDL was higher in the probiotic group.

Previous research has shown that it is not the body fat alone but the increased low grade inflammation and metabolic dysfunction causing disease. This promotes insulin resistance in the liver and the release of inflammatory mediators from the adipose tissue. In addition, increased intestinal permeability allows translocation of proinflammatory lipopolysaccharides.

There is evidence that age-related changes in the gut microbiome may be related to elevated inflammatory makers. As one ages, the gut has an increase in interleukin 6 (IL-6) which causes the immune system to release IL-6 and trigger inflammation. Increased levels of IL-6 directly lead to increased intestinal permeability with no physical differences seen in its structure. Probiotics have the potential to rebalance gut microbiota and modulate gut immune response inhibiting the NF-κB pathway.

Other research has indicated that obesity has a microbial component that alters the caloric extraction from ingested food. For example, if one has more Bacteroidetes bacteria, the individual tends to be leaner. High Firmicutes:Bacteroidetes ratios have been known to increase the caloric extraction from food and these individuals tend to be more obese. This also ties together the importance of dietary fiber, prebiotics, and weight loss.

I remember when I was at a probiotic workshop a few years ago at Yale, Max Nueuwdrop, MD, PHD, an internist and endocrinologist, from Amsterdam presented on this topic. He went into detail on the microbiota and metabolism.  He described how butyrate, a SCFA, improved insulin resistance and brown fat activation. In general, low short chain fatty acids (SCFAs) are associated with low diversity and abundance of the commensal bacteria. When patients introduce probiotics and increase their dietary fiber intake by consuming fruits and vegetables, the beneficial bacteria butyrate, and SCFAs increase.

Probiotics help encourage microbial diversity, especially if the probiotic supplement is of mixed species. In ecological terms, it is more stable to have diverse populations in any ecosystem. The same is true for the gastrointestinal microbiome. This large scale study demonstrates the potential benefits of probiotic supplementation in patients with obesity and hypertension.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Lau E, Neves JS, et al. DIM, Probiotic Ingestion, Obesity, and Metabolic-Related Disorders: Results from NHANES, 1999–2014. Nutrients 2019, 11(7), 1482.

New study investigates the effect of DHA and Delta-tocotrienol in breast cancer

Breast cancer is the most common cancer in the world. Although there has been progress in cancer treatment, triple negative breast cancer remains a challenge. Lipid metabolism is more activated in this form of breast cancer and understanding how bioactive molecules can be targeted and modulated is essential to improving patient outcomes.

DHA and Delta-tocotrienols have been largely studied separately on their effect on tumor growth reduction combined with conventional therapies.

According to a new study published two weeks ago in Nutrients, researchers demonstrated that the combination of DHA and Delta-tocotrienol shows promise in breast cancer.

Tocotrienols are specific isomers of vitamin E that have been previously shown to reduce inflammation and oxidative stress in chronic disease. In addition, tocotrienol isomers have superior antioxidant, anticancer, and anti-inflammatory effects compared to tocopherols.  DHA has been used successfully as an adjunct to cancer treatments increasing their efficacy without adverse effects. The combination of both of these weakly investigated, however, it has been described to have a positive synergistic effect.

This study demonstrated that DHA and Delta-tocotrienol triggered a reduction in lipid droplet biosynthesis, a marker of breast cancer aggressiveness where this was not seen with DHA alone suggesting that the combination may have an impact on breast cancer aggressiveness.

Triple negative breast cancer has a complex biology and does not respond to hormonal therapies. This type of cancer has a poorer outcome. This study demonstrates that cell proliferation can be altered through lipid droplet modulation, which plays a role in breast cancer aggressiveness.

DHA is known for inducing reactive oxygen species in breast cancer cells, however, Delta-tocotrienol reduces reactive oxygen species due to its powerful antioxidant and anti-inflammatory properties. This further supports that Delta-tocotrienol can modulate DHA’s effects on lipid droplet biogenesis.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Pizato N, Kiffier LFMV, et al.  Omega 3-DHA and Delta-Tocotrienol Modulate Lipid Droplet Biogenesis and Lipophagy in Breast Cancer Cells: the Impact in Cancer Aggressiveness. Nutrients. 2019 May 28; 11(6).

New study identifies how microbiome is disrupted in inflammatory bowel disease

  • Inflammatory bowel disease (IBD) is an autoimmune condition where in most cases there are multiple triggers chronically stimulating the immune system over a long period of time in multiple ways and the immune system gets into overloaded, overwhelmed state and loses its ability to function leading to chronic inflammation causes symptoms such as diarrhea, abdominal pain, and other debilitating symptoms and anemia.

According to a study published last Wednesday in Nature, researchers demonstrated the chemical and molecular events that shift the microbiome and exacerbate disease activity in patients with IBD.

Although previous research has shown differences in the gut microbiome in IBD patients, this study investigated how the microbiome changes contributes to an inflammatory response.

This study included 132 individuals followed for one year and compared Crohn’s disease and ulcerative colitis patients to a control group that did not have IBD. Each individual provided stool samples every two weeks, blood samples every 3 months, and colon biopsies at the start of the study. A total of 2,965 stool, biopsy, and blood samples were analyzed along with molecular, cellular, and clinical tools to understand the detailed biochemistry of the disease.

It is important to know what bacteria are present and how these bacteria shift as the patient’s symptoms exacerbate or improve.

As a result, during periods of disease activity patients with IBD had higher levels of polyunsaturated fatty acids, including adrenate and arachidonate. In addition, nicotinuric acid was found almost exclusively in the stool of patients with IBD and that levels of vitamins B5 and B3 were insufficient in IBD patients. Also, a group of bacteria related to the genus Subdoligranulum commonly found in almost every individual is depleted during inflammation, which have not been previously isolated.

Previous research has identified that in healthy people, the gut microbiome was much more stable than those with IBD. Patients with IBD have dramatic shifts in their microbiomes with some bacteria disappearing almost completely at times.

Medication to treat IBD can also affect the microbiome. Individuals who take steroids for part of their treatment have more fluctuations in their microbiome and those who were experiencing a flare-up in their symptoms are more likely to have dramatic fluctuations in their microbiome.

These results further support the functional medicine approach to assess the microbiome regularly in these patients so one can take an individualized approach to manipulate the microbiome and keep IBD patients in remission, especially if medications like corticosteroids can be shift the microbiome leading to an exacerbation of the disease.

High dose probiotics, fish oil, glutamine, and mucilaginous botanicals are helpful in immunomodulation and for their anti-inflammatory properties. Other common deficiencies include magnesium, vitamin D, and magnesium. A specific carbohydrate diet (SCD) or elimination diet can improve gastrointestinal function and decease disease activity.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Jason Lloyd-Price, Cesar Arze, et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature, 2019; 569 (7758): 655 DOI: 10.1038/s41586-019-1237-9

New review demonstrates the benefits of resveratrol in patients with metabolic syndrome

Resveratrol is a polyphenol with powerful antioxidant and anti-inflammatory properties.  It is naturally found in nuts, berries, and grapes skin but the concentration is low. Studies have been widely publicized for its cardiovascular, anti-carcinogenic, and anti-aging benefits.  Research has also shown significant benefits in cognitive diseases and inflammatory disorders.

Previous research with resveratrol has demonstrated improvements in dysglycemia and insulin sensitivity, however, there has been some inconsistency in results.

According to a new review published last Tuesday in Nutrients, researchers reviewed 16 controlled trials and evaluated the correlation between resveratrol supplementation with metabolic assessments such as body weight, waist circumference, systolic blood pressure, HDL, total cholesterol, triglyceride, and glucose levels.  

As a result, there was significant effect of resveratrol supplementation on reducing blood glucose levels, body weight, waist circumference, and triglycerides. There was also a positive effect on increasing HDL levels but not on total cholesterol. These effects were seen in dosing at 500 mg or greater for over a 10-week period.

Resveratrol activates AMPK which upregulates mitochondrial biogenesis and stimulates glucose uptake and fatty acid oxidation improving insulin sensitivity. This mechanism modifies the body’s energy balance, body fat accumulation, and increases triglyceride metabolism. It also activates sirtuins, which can increase insulin sensitivity and protect against oxidative damage. These are the same proteins activated by caloric restriction and exhibit anti-atherosclerotic effects. Resveratrol mitigates vascular nitric oxide production and endothelial dysfunction demonstrating its beneficial effects on the underlying issues of metabolic syndrome.

These results support resveratrol supplementation as a potential strategy for improving glucose control and insulin sensitivity as well as mitigating arterial stiffness and oxidative damage in patients with metabolic syndrome. Other nutrients that should be considered include inositol, tocotrienols, fish oil, probiotics, and resistant starch.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS Source: Asgary S, Karimi R, et al. Effect of resveratrol on metabolic syndrome components: A systemic review and meta-analysis. Rev Endocr Metab Disord. 2019 May 7.

New study demonstrates the correlation between vitamin C levels and cognitive function

Many chronic conditions typically have increased nutrient demands than in healthy individuals. These are considered conditionally essential nutrients. There is either a disruption in metabolic processes, underlying inflammation, oxidative stress, or an inability to meet the metabolic demands with the current nutrient reserves.

In a study published earlier this month in Frontiers in Aging Neurosceince, researchers demonstrated a significant association between plasma vitamin C levels and performance on tasks involving attention, focus, working memory, decision speed, delayed and total recall, and recognition.

Previous research has shown that patients with Alzheimer’s have significantly lower plasma levels of folate, vitamin B12, and vitamin C. It is essential to protect against oxidative damage through the diet and supplementation. It is also important to note that vitamin C and folate concentrations are much higher in the brain than in the plasma.

This cross-sectional study included 81 healthy individuals ages 24 to 96 years of age with a range of plasma vitamin C concentrations. Cognitive assessments included The Swinburne-University-Computerized-Cognitive-Assessment-Battery (SUCCAB) and two pen and paper tests as well as the Symbol-Digits-Modalities-Test (SDMT) and Hopkins-Verbal-Learning-Test-Revised (HVLT-R). Individuals were divided into two groups. Those with a plasma vitamin C level of greater than 28 μmol/L (adequate) and those less than 28 μmol/L (deficient).

The SUCCAB assessment identified a significantly higher performance ratio in the group with adequate vitamin-C levels compared to those in the deficient group on reaction time, immediate recognition memory and delayed recognition tasks.

There were significantly higher scores in immediate recall on the HVLT-R, delayed recall, total recall in those with adequate plasma Vitamin-C concentrations. Similar results were seen on the SDMT.

Vitamin C should be assessed and supplemented accordingly and incorporated in the diet in all individuals but especially patients at risk for cognitive decline. Since humans cannot synthesize their own vitamin C, it is common to have an insufficiency especially in older individuals with chronic disease. Vitamin C levels in found in the tissues of the brain and muscle may be reduced to 25% of that of childhood. Serum vitamin C or oxidative stress markers looking at the functional need for water soluble antioxidants like 8-hydroxy-2-deoxyguanosine (8-OHdG) should be considered.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Travica N, Ried K, et al. Plasma Vitamin C concentrations and Cognitive Function: A Cross-Sectional Study. Front Aging Neurosci. 2019 Apr 2;11:72.

 

 

 

 

New study demonstrates the benefits of resistant starch in patients with chronic kidney disease

Over 10% of the adult pong causes of end-stage kidney disease are due to type II diabetes and hypertension. There can also be a dysbiosis of the gut microbiome along with inflammation and oxidative stress that can play a role as well. In addition, environmental toxins and proton pump inhibitor (PPI) use have also been linked to CKD.

According to a new study published in Nutrition & Metabolism, researchers demonstrated the benefit of resistant starch on traditional kidney laboratory biomarkers.

A high fiber diet leads to the production of short chain fatty acids (SCFAs) in the gastrointestinal tract. These play an essential role in T regulatory cell activation, which regulates the intestinal immune system. If there is dysregulation in the immune system, there can be increase inflammation seen in CKD.

Previous research has demonstrated that a high fiber diet can mitigate disease severity and kidney dysfunction in patients with CKD.

This study was a double-blinded randomized clinical trial consisting of 50 patients in end stage renal disease. There were 25 patients in each group that either took a resistant starch enriched diet or placebo over an 8-week period.  This was 20-25 gram, 60% resistant starch cracker or a 20-25 gram, waxy corn starch, cracker. Each participant received a 20 gram cracker the first 4 weeks followed by a 25 gram cracker the remainder of the study. Laboratory assessment of BUN, creatinine, uric acid, hemoglobin, hemocrit, uric acid, hs-crp, p-cresol, indoxyl sulfate, and bone markers were measured at baseline and at the end of the study.

As a result, there was a significant reduction of creatinine, uric acid, and p-cresol levels in the resistant starch group. There was not a significant change in the other parameters.

There were no side effects including gastrointestinal intolerance with the recommended doses of resistant starch. Based on these results as well as the safety of diet with resistant starch, it makes sense that this a great addition in the treatment of chronic kidney disease. Other nutrients to consider include fish oil, phosphatidylcholine, and n-acetyl-cysteine or glutathione.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Khosroshahi HT, Abedi B, et al. Effects of fermentable high fiber diet supplementation on gut derived and conventional nitrogenous product in patients on maintenance hemodialysis: a randomized controlled trial. Nutr Metab (Lond). 2019 Mar 12;16:18.

 

 

New study demonstrates curcumin improves dyslipidemia and inflammatory markers in patients with diabetes

According to a new study published last Tuesday, researchers demonstrated the effect of curcumin supplementation on inflammatory markers and lipid profiles of patients with diabetes.

There are only a few natural products that have demonstrated the wide range of protective properties as curcumin. Turmeric has three main bioactive components which are curcumin, desmethoxycurcumin and bisdemethoxycurcumin. These curcuminoids have many biological effects including anti-inflammatory, antioxidant, antitumor, antibacterial, and antiviral properties.

This double-blind randomized clinical trial included forty-four patients with Type 2 diabetes. Each patient was randomly assigned to take 1500 mg of curcumin or a placebo per day for a ten-week period. Anthropometric measurements were measured at baseline and at the end of the study. Laboratory assessment including a lipid panel, high-sensitivity C-reactive protein (hs-crp), and adiponectin were measured at baseline and at the end of study.

As a result, there was a significant reduction in serum triglycerides in the patients who consumed the curcumin compared to the beginning of the study. In addition, hs-crp levels decreased as expected and there was an increase in adiponectin, a fat burning hormone, compared to the placebo. These results indicate the benefits of curcumin supplementation in patients with diabetes.

Previous studies have demonstrated that curcumin promotes changes in the expression of genes involved in cholesterol synthesis such as the LDL receptor mRNA, HMG CoA reductase, SREBP, cholesterol 7 alpha hydrolyze, PPAR, and LXR1.1,2 One human study demonstrated that 500 mg of curcumin per day increased HDL cholesterol by 29% and reduced total cholesterol by 12%.2

In addition, I shared a study from Complementary Therapies in Medicine from 2017 on curcumin and dyspildemia in diabetic patients. In this study, researchers demonstrated that curcuminoid supplementation of 1000 mg daily for 12 weeks can reduce lipoprotein(a) and increase HDL-C.

Health care providers have many tools today to assess cardiovascular health and support the body’s physiology. It is essential to perform a thorough assessment for these patients. This may include looking at advanced lipid profiles, inflammatory markers (ferritin, hs-CRP, fibrinogen), nutrient markers (magnesium, potassium, selenium, copper, folate, B12, B6, and zinc), fat soluble vitamins (CoQ10, vitamin D, vitamin K, Vitamin A, and tocotrienols), oxidative stress factors (homocysteine, insulin, and lipid peroxidases), heavy metals, and fatty acid profiles. A successful treatment approach should include investigation into these factors.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Adibian M, Hodaei H, et al. The effects of curcumin supplementation on high-sensitivity C-reactive protein, serum adiponectin, and lipid profile in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial. Phytother Res. 2019 March 12.

 Ferguson J, Stojanovski E et al. Curcumin potentiates cholesterol-lowering effects of phytosterols in hypercholesterolaemic individuals. A randomised controlled trial. Metabolism 2017 Dec 29.

  1. Houston MC, Fazio S, Chilton FH, Wise DE, Jones KB, Barringer TA, and Bramlet DA. Non pharmacologic treatment of dyslipidemia. Prog Cardiovasc Dis 2009; 52: 61–94.
  2. Soni KB and Kuttan R. Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. Indian J Physiol Pharmacol 1992; 36(4): 273–75.

New study demonstrates the effect of vitamin D on intestinal inflammation in IBD

Inflammatory bowel disease (IBD) is an autoimmune condition where in most cases there are multiple triggers chronically stimulating the immune system over a long period of time in multiple ways and the immune system gets into overloaded, overwhelmed state and loses its ability to function leading to chronic inflammation causes symptoms such as diarrhea, abdominal pain, and other debilitating symptoms and anemia.

Vitamin D deficiency has been linked to many autoimmune diseases, including type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, and IBD, with studies finding a higher prevalence of these diseases in those who are deficient in vitamin D.

More and more data has demonstrated that Vitamin D supplementation may lengthen the remission in patients with IBD.

According to a study published earlier this month in the Journal of Crohn’s and Colitis, researchers investigated the impact if vitamin D on the gut microbiome and inflammation.

This was a small study including twenty five patients. Eight individuals had active ulcerative colitis, nine were in remission, and eight did not have IBD and were controls. Inflammatory markers and the gut microbiome were analyzed. All of the patients were prescribed 40,000 IUs of vitamin once a week for an 8 week period.

As a result, vitamin D levels increased from 13.6 ng/ml to 44.4 ng/ml. In patients with active IBD, fecal calprotectin levels reduced from median 275 to 111µg/g, platelet count reduced, and albumin increased. These biomarkers did not change in patients with inactive ulcerative colitis or in the control group. In addition, there were no changes in overall bacterial diversity, however, there was a significant increase in Enterobacteriaceae bacteria in patients with ulcerative colitis.

Overall vitamin D supplementation was associated with reduced intestinal inflammation in patients with active ulcerative colitis as well as increase in Enterobacteriaceae but no change in diversity of the gut microbiome.

Most patients I find need anywhere form 5,000-10,000 IUs/day of vitamin D. It is crucial to use a supplement that combines vitamin K or supplement with a separate vitamin K supplement. There are intricate relationships between fat-soluble vitamins and it is important take this into account with dosing vitamin D supraphysiologically.

According to a study in The Journal of Immunology, March 2012, researchers demonstrated that the highest levels of inflammatory inhibition occurred at 50 ng/ml. Therefore, there may have been a more significant outcome this study if vitamin D was dosed 10,000 IU daily or 50,000IU/week.

One must also investigate into the other potential environmental triggers that can cause inflammation such as, food sensitivities, toxins, and molds. Also, stool testing is essential as one can rule of bacterial infections and dysbiosis as well as assess inflammatory, immune, digestion, and absorption markers.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Garg M, Hendy P, et al. The effect of vitamin D on intestinal inflammation and faecal microbiota in patients with ulcerative colitis. J Crohns Colitis. 2018 May 3. doi: 10.1093/ecco-jcc/jjy052

Resveratrol improves insulin sensitivity and glucose control in patients with diabetes

Resveratrol is a polyphenol with powerful antioxidant and anti-inflammatory properties.  It has been widely publicized for its cardiovascular, anti-carcinogenic, and anti-aging benefits.  

Resveratrol activates sirtuins, which can increase insulin sensitivity and protect against oxidative damage. Previous research with resveratrol has demonstrated improvements in dysglycemia and insulin sensitivity, however, there has been some inconsistency in results.

According to a new review published 3 weeks in Nutrition & Metabolism, researchers demonstrated that resveratrol does improve glycemic control and insulin sensitivity in individuals with type II diabetes.

This review consisted of 9 RCT studies, dosing ranges from 8 mg/d to as high as 3 g/d with a duration of 4 weeks to 12 months. The overall results demonstrated that resveratrol significantly reduces fasting glucose levels but only at a dosage of 100 mg/d or more. In addition, HOMA-IR, fasting insulin levels, and blood pressure was also reduced by resveratrol.

In addition, a previous study published earlier this year in the International Heart Journal, researchers demonstrated resveratrol’s benefits in improving arterial stiffness and reduced oxidative damage in patients with type II diabetes. This study used the same dosage of 100 mg which has been shown to reduce fasting glucose levels.

Resveratrol can act through several mechanisms, including binding and activating estrogen receptors to increase nitric oxide bioavailability and facilitate the vasodilatation. In addition, it decreases reactive oxygen species production in vascular endothelial cells. Oxidative stress is elevated in chronic disease such as obesity and diabetes. 

These results support resveratrol supplementation as a potential strategy for improving glucose control and insulin sensitivity as well as mitigating arterial stiffness and reducing blood pressure and oxidative damage with patients with type II diabetes.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Zhu X, Wu C et al. Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: systematic review and meta-analysis. Nutrition & Metabolism. 2017 Sept 22;14:60.

New study demonstrates selenium reduces antibody levels in Hashimoto’s patients

Hashimoto’s is one of the most common autoimmune diseases. Autoimmunity can occur a few different ways, but eventually the thyroid gland progressively becomes underactive due to antibody and cell mediated autoimmune processes.

Environmental triggers are what integrative doctors mainly work with in functional medicine to healthy address the dysfunction in autoimmune disease. These can be food triggers such as gluten or food sensitivities that can trigger inflammation as well as anything coming in with the food such as toxins or molds. In addition, the nutrient status of the person. This can be antioxidant status, vitamins, essential fatty acids, vitamin D, etc. Also, gut health. This includes “leaky gut” and dysbiosis. There are also toxins that can be affect the status of the immune system. These are heavy metals, xenobiotics, as well as the total toxic burden in the body.

According to a study published last month in Advanced Biomedical Research, researchers demonstrated that selenium reduces antibody levels in patients with Hashimoto’s thyroiditis.

In this study, seventy patients ranging from 18 to 60 years of age with Hashimoto’s were divided into two groups. One group received 200 mcg of selenium with levothyroxine and the other group received a placebo along with the medication. Laboratory assessment included serum selenium levels, TSH, freeT4, free T3, and thyroid antibodies at baseline and three months later.

As a result, the mean thyroid peroxidase antibody level was significantly lower after treatment in the selenium group. Selenium is involved in the metabolism and regulation of thyroid hormones and is an antioxidant which has protective properties. 

Another nutrient to consider is inositol. Myo-inositol is a second messenger regulating several hormones such as insulin and TSH.

A previous study published last year in the European Review for Medical and Pharmacological Sciences demonstrated that inositol at 600 mg a day and selenium at 83 mcg per day significantly reduced TSH levels in Hashimoto’s patients with subclinical hypothyroidism and increased thyroid hormone concentrations. In addition, there was a reduction in TPO and thyroglobulin antibody concentrations.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Kachouei A, Rezvanian H, et al. The Effect of Levothyroxine and Selenium versus Levothyroxine Alone on Reducing the Level of Anti-thyroid Peroxidase Antibody in Autoimmune Hypothyroid Patients. Advanced Biomedical Research. 2018 January 22;7:1. doi: 10.4103/2277-9175.223735