T-150 [Discontinued] by XYMOGEN

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Addison disease. Although there has been interest in using oral adrenal extract for Addison disease, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose.
• Allergic rhinitis (hay fever). Although there has been interest in using oral or sublingual adrenal extract for allergic rhinitis, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose.
• Asthma. Although there has been interest in using oral adrenal extract for asthma, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose.
• Atopic dermatitis (eczema). Although there has been interest in using oral adrenal extract for eczema, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose.
• Depression. Although there has been interest in using sublingual adrenal extract for depression, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose.
• Fatigue. Although there has been interest in using oral or sublingual adrenal extract for fatigue, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose.
• Hyperkalemia. Although there has been interest in using intravenous adrenal extract for hyperkalemia, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose.
• Hypoglycemia. Although there has been interest in using sublingual adrenal extract for hypoglycemia, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose.
• Hypotension. Although there has been interest in using sublingual adrenal extract for hypotension, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose.
• Miscarriage. Although there has been interest in using intravenous adrenal extract for miscarriage, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose.
• Opioid withdrawal. Although there has been interest in using sublingual adrenal extract for opioid withdrawal, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose.
• Psoriasis. Although there has been interest in using oral adrenal extract for psoriasis, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose.
• Rheumatoid arthritis (RA). Although there has been interest in using oral adrenal extract for RA, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose.
• Stress. Although there has been interest in using oral or sublingual adrenal extract for stress, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose.
• Ulcerative colitis. Although there has been interest in using intravenous adrenal extract for ulcerative colitis, there is insufficient reliable information about the clinical effects of adrenal extract for this purpose. More evidence is needed to rate adrenal extract for these uses.

(Read more about ADRENAL EXTRACT)

POSSIBLY INEFFECTIVE

• Human papillomavirus (HPV). Topical carrageenan gel does not seem to reduce the risk of anal HPV in males who have sex with males. Details: A clinical study in adult males who have sex with males shows that applying 15 mL of carrageenan 1.4% gel to the anus, condom, or partners' penis prior to receptive anal intercourse does not decrease the rate of anal HPV when compared with placebo, regardless of HPV strain, HPV vaccination status, or HIV status. Although patients were enrolled for an intended duration of 1 year, the study was terminated early due to a lack of observed benefit and potential safety concerns, resulting in a median follow-up of 8 months. A total of 60% of patients in the treatment group reported adverse effects, compared with 40% of patients in the placebo group (107851). Additionally, the prevalence of HPV at baseline was 61%, which may have reduced the study's ability to identify an effect.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Common cold. Evidence on the use of intranasal iota-carrageenan for improving symptoms of the common cold is conflicting. Details: A small clinical study in patients with early symptoms of the common cold shows that spraying a saline solution containing iota-carrageenan 0.12% into the nose three times daily for 4 days seems to reduce total symptoms during days 2-4 when compared with using a plain saline spray. However, in a larger clinical trial using the same methods, there were no differences between placebo and treatment groups. Furthermore, neither study noted an improvement in total cold symptoms over 7-10 days (99449,99450). In children with the common cold, spraying a saline solution containing iota-carrageenan 0.12% seemed to be no better for improving cold symptoms than using plain saline spray (99451). Some research suggests that carrageenan might benefit patients with a confirmed viral infection. In a clinical study in patients with symptoms of a common cold and a laboratory-confirmed viral infection, using a specific nasal spray (Coldamaris) containing carrageenan 0.12% three times daily for 7 days reduced symptom duration by about 2 days when compared with using a saline nasal spray. However, there was no difference in disease duration when all patients were considered, regardless of viral infection status (99452). Furthermore, the validity of this study is limited by the changing definitions for disease duration and primary outcome over the course of the study.
• Coronavirus disease 2019 (COVID-19). There is limited evidence on the intranasal use of iota-carrageenan for the prevention of COVID-19. Details: A clinical study in healthcare professionals working with patients hospitalized for COVID-19 shows that using a nasal spray containing iota-carrageenan 0.17% as 1 puff in each nostril 4 times daily (providing 1 mg daily) for 21 days decreases the absolute rate of confirmed, symptomatic COVID-19 to 1%, compared with 5% of patients in the placebo group. This suggests that 25 people would need to use this nasal spray to prevent one infection (107852). The validity of this study is limited due to the lack of baseline viral testing and short duration; additionally, asymptomatic COVID-19 infections may be underreported due to study design.
• Cough. Although there is interest in using oral carrageenan for cough, there is insufficient reliable information about the clinical effects of carrageenan for this condition. More evidence is needed to rate the effectiveness of carrageenan for these uses.

(Read more about CARRAGEENAN)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Hypercholesterolemia. It is unclear if oral dulse is beneficial in patients with hypercholesterolemia. Details: A moderate sized clinical study in patients with hypercholesterolemia shows that taking dulse powder 2 grams daily for 8 weeks does not improve low-density lipoprotein (LDL) cholesterol levels or glycemic control when compared with placebo. However, there was a small beneficial effect on triglyceride levels in females (103323).
• Iodine deficiency. Although there has been interest in using oral dulse for the prevention of iodine deficiency, there is insufficient reliable information about the clinical effects of dulse for this purpose. More evidence is needed to rate dulse for these uses.

(Read more about DULSE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging skin. Although there has been interest in using topical Fucus vesiculosus for aging skin, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose.
• Cardiovascular disease (CVD). Although there has been interest in using oral Fucus vesiculosus for CVD, including atherosclerosis and hypertension, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose.
• Constipation. Although there has been interest in using oral Fucus vesiculosus for constipation, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose.
• Diarrhea. Although there has been interest in using oral Fucus vesiculosus for diarrhea, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose.
• Dyspepsia. Although there has been interest in using oral Fucus vesiculosus for dyspepsia, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose.
• Hypercholesterolemia. It is unclear if oral Fucus vesiculosus is beneficial in hypercholesterolemia. Details: A small clinical study in patients with obesity or overweight and low-density lipoprotein (LDL) cholesterol levels exceeding 77 mg/dL shows that taking a polyphenol-rich extract of Fucus vesiculosus (Maritech Synergy, Marinova) 2000 mg, providing 560 mg of polyphenols, daily for 12 weeks increases levels of high-density lipoprotein (HDL) cholesterol by 10%, compared with 2% in those receiving placebo. No differences were observed for total cholesterol, LDL cholesterol, or triglycerides (106723).
• Hypothyroidism. Although there has been interest in using oral Fucus vesiculosus for hypothyroidism, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose.
• Impaired glucose tolerance (prediabetes). Oral Fucus vesiculosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with prediabetes and dysglycemia shows that taking a specific product (Gdue, Aesculapius), containing extracts of Fucus vesiculosus and Ascophyllum nodosum in a 5:95 ratio along with chromium picolinate three times daily for 6 months reduces fasting and postprandial blood glucose, glycated hemoglobin (HbA1c), insulin, and insulin resistance when compared with placebo (100847). It is unclear if these effects are due to Fucus vesiculosus, other ingredients, or the combination. Another small clinical study in adults with prediabetes and also overweight or obese shows that taking a specific product (InSea2, InnoVactiv Inc.) containing 500 mg of Fucus vesiculosus and Ascophyllum nodosum extracts daily for 12 weeks reduces postprandial blood glucose but does not improve fasting blood glucose, HbA1c, body weight, lipids, or blood pressure when compared with placebo (110560).
• Iodine deficiency. Although there has been interest in using oral Fucus vesiculosus for iodine deficiency and goiter, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose.
• Metabolic syndrome. Oral Fucus vesiculosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Observational research in adults with one or more components of metabolic syndrome has found that taking a specific combination product (Gdue, Aesculapius) containing extracts of Fucus vesiculosus and Ascophyllum nodosum in a 5:95 ratio along with chromium picolinate two to three times daily with meals for around 6 months is associated with reductions in body weight by 7.3 kg, waist circumference by 7.5 cm, fasting blood glucose by 16 mg/dL, glycated hemoglobin (HbA1c) by 0.55%, systolic blood pressure by 7 mmHg, diastolic blood pressure by 4 mmHg, low-density lipoprotein (LDL) cholesterol by 18 mg/dL, and 10-year cardiovascular risk scores by 1.8% when compared to baseline (110559). It is unclear if these effects are due to Fucus vesiculosus, other ingredients, or the combination. Further, the validity of these findings is limited by a lack of control group.
• Obesity. Oral Fucus vesiculosus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in moderately overweight females shows that seaweeds such as Fucus vesiculosus, taken in combination with lecithin and vitamins for up to 2 years, do not result in sustained weight loss when compared to baseline (13663). Another small clinical study in adults with prediabetes and also overweight or obese shows that taking a specific product (InSea2, InnoVactiv Inc.) containing 500 mg of Fucus vesiculosus and Ascophyllum nodosum extracts daily for 12 weeks does not reduce body weight, body mass index (BMI), body fat, lipids, blood pressure, or measures of glycemic control when compared with placebo (110560).
• Wound healing. Although there has been interest in using topical Fucus vesiculosus for wound healing, there is insufficient reliable information about the clinical effects of Fucus vesiculosus for this purpose. More evidence is needed to rate Fucus vesiculosus for these uses.

(Read more about FUCUS VESICULOSUS)

LIKELY EFFECTIVE

• Iodine deficiency. Oral iodine supplements, including iodized salt, are effective for improving iodine status and reducing goiter size in adults and children. Iodine supplementation is also recommended during pregnancy in areas at risk for iodine deficiency. Details: Iodine deficiency is associated with several adverse outcomes. The earliest clinical symptom of iodine deficiency is low circulating thyroid hormone and thyroid stimulating hormone (TSH), followed by thyroid goiter (7135,16747,91398). Iodine deficiency and subsequent hypothyroidism can lead to anovulation, infertility, autoimmune thyroiditis, and gestational hypertension. Iodine deficiency is also associated with increased risk of thyroid cancer (16747). Clinical research shows that taking iodine supplements, including iodized salt, improves iodine status and reduces goiter size in adults with iodine deficiency (16747,55919,103071). Studies also show that taking iodine supplementation, including iodized salt, in areas of endemic iodine deficiency, reduces goiter size in children (16747,55919). When taken during pregnancy for iodine deficiency, iodine supplements and iodized salt reduce both maternal and newborn thyroid size and thyroglobulin; however, the effect on maternal TSH is inconsistent (91399,103070). Although some clinical studies and one analysis show that perinatal use of iodine has no effect on the incidence of thyroid disorders during pregnancy (91399,97240,97241), one analysis shows that iodine supplementation reduces the risk of postpartum hyperthyroidism by 68% when compared with placebo (97240). Taking iodine supplementation before 12 weeks' gestation appears to be more effective than when taken later in pregnancy. Perinatal iodine supplementation has no effect on preterm birth rate (97240,97241). Evidence is limited to females with mild-moderate iodine deficiency; the routine use of iodine supplementation during pregnancy has not been extensively studied. For example, the effect of perinatal supplementation on newborn neurocognitive development is conflicting and the evidence is generally low quality (55976,97241,105880,108706). Despite the limited evidence, iodine supplementation is recommended in areas at risk of deficiency.
• Radiation exposure. Oral potassium iodide prevents thyroid uptake of radioactive iodine. However, it does not protect against other sources of radiation. Details: Taking potassium iodide is effective for preventing the uptake of radioactive iodine by the thyroid (7517,7518). Doses of potassium iodide protect for about 24 hours. Therefore, it should be taken daily until the risk of radiation exposure no longer exists (17575,17576).

POSSIBLY EFFECTIVE

• Conjunctivitis. Ophthalmic povidone-iodine solution seems to reduce the risk of conjunctivitis in infants. It may also improve the resolution of acute conjunctivitis in adults. It is unclear if it is beneficial in patients with adenoviral conjunctivitis. Details: A meta-analysis of low-quality clinical trials shows that povidone-iodine solutions are more effective than silver nitrate for preventing neonatal conjunctivitis. However, povidone-iodine solutions are not more effective than erythromycin or chloramphenicol (56084). Povidone-iodine in combination with dexamethasone also seems to be helpful in adults. A clinical trial in patients with acute viral conjunctivitis shows that applying povidone-iodine 0.6% with dexamethasone 0.1% four times daily for 4 days improves clinical symptoms and eradiation of viral counts when compared with placebo control (103075). A small clinical study in adults with adenoviral conjunctivitis shows that administering 4-5 drops of a povidone-iodine 5% eye drop solution within 4 days of symptom onset decreases viral load, mucoid discharge, and bulbar edema and redness on day 4 of a 21-day follow-up period, but at no other time points, when compared with a single dose of artificial tears (108705). Due to the single-dose nature of this study, the effects of continued administration are unclear.
• Diabetic foot ulcers. Topical iodine seems to help with the management of diabetic foot ulcer wounds. Details: A small clinical study in patients with diabetic foot ulcers shows that topically applying cadexomer iodine ointment (Iodosorb) for 12 weeks seems to improve healing to a similar degree as using standard treatment with gentamicin solution, streptokinase, and/or dry saline gauze (2200).
• Endometritis. Topical application of iodine prior to cesarean delivery seems to reduce the risk of endometritis. Details: A meta-analysis of eight clinical trials shows that vaginally applying povidone-iodine 1% to 10% solution immediately before cesarean delivery reduces the risk of post-cesarean endometritis by 62% when compared with saline or no cleaning. It also reduces postoperative fever by 13% and wound infection by 23% (99794). These findings are consistent with other meta-analyses (56080,103076). There seems to be no difference in benefit whether povidone-iodine 1%, 5%, or 10% is used. A network meta-analysis of clinical studies in patients having cesarean delivery suggests that povidone-iodine is no better at preventing endometritis than using chlorhexidine or metronidazole; however, there may not have been sufficient power to detect a difference (103076).
• Fibrocystic breast disease. Oral iodine seems to reduce breast pain in patients with fibrocystic breast disease. Details: Preliminary clinical research in patients with fibrocystic breast disease shows that taking sodium iodide, protein bound iodide, or molecular iodine for 6 months or longer improves mastalgia and reduces breast nodules when compared with baseline or control. Molecular iodine in doses of 70-90 mcg/kg appears to be more effective and better tolerated than the other forms (2197). Another clinical study in patients with cyclic mastalgia due to fibrocystic breast disease shows that taking tablets containing molecular iodine 3000-6000 mcg daily for 5 months reduces pain, tenderness, and nodularity in patients with cyclic mastalgia when compared with placebo. However, a lower dose of 1500 mcg daily does not appear to be beneficial (55960).
• Oral mucositis. Rinsing the mouth with a povidone-iodine solution may prevent oral mucositis from radiochemotherapy. Details: Small clinical studies in patients receiving radiation and chemotherapy for cancer shows that using an oral povidone-iodine rinse seems to reduce the risk for oral mucositis when compared with using sterile water (2198,2199).
• Periodontitis. Rinsing with povidone-iodine solution in addition to scaling and root planing seems to be modestly beneficial in patients with periodontitis. Details: A meta-analysis of mostly small clinical studies in patients with chronic periodontitis suggests that rinsing with povidone-iodine 0.1% to 10% during scaling and root planing modestly reduces the periodontal pocket depth when compared with rinsing with water or saline solution (56072).
• Postoperative infection. Povidone-iodine antisepsis prevents postoperative infection when compared with inactive controls such as normal saline and water. However, it is unclear how it compares to active controls such as chlorhexidine; practice guidelines are conflicting. Details: A meta-analysis of clinical research shows that intraoperative application of povidone-iodine reduces the risk of surgical site infection by approximately 40% when compared with saline or no irrigation (56088). However, research comparing povidone-iodine with other antiseptics such as chlorhexidine is conflicting, as are official guidelines for surgical antisepsis. Many of these discrepancies seem to be related to the presence or absence of alcohol in the preparation. A meta-analysis of clinical research comparing aqueous or alcohol-based povidone-iodine shows that using alcohol-based chlorhexidine for skin antisepsis is more effective for preventing postoperative surgical site infections and may be associated with a lower overall positive culture rate. However, since evidence for both aqueous and alcohol-based solutions of povidone-iodine were included in this study, it is unclear if this may have affected outcomes (108710). The National Institute for Health and Care Excellence (NICE) Guideline recommends chlorhexidine solution as the first choice for preparing the skin for surgery, with povidone-iodine solution as a second-line option. The antiseptic solutions are recommended to be alcohol-based as long as the surgical site is not near a mucous membrane (105906). The World Health Organization (WHO) guidelines also recommend alcohol-based chlorhexidine solutions over either alcohol-based or aqueous povidone-iodine for preventing surgical site infections. However, some experts have expressed concern that these recommendations are based on faulty evidence, as some studies used povidone-iodine preparations with lower alcohol amounts than their comparator groups (105898). In fact, the guideline from the Centers for Disease Control and Prevention (CDC) does not differentiate between povidone-iodine and chlorhexidine antiseptic solutions as long as they are alcohol-based (105905).
• Thyroid storm. Oral iodine is recommended as an adjunct to standard treatment for thyroid storm. Details: The American Thyroid Association (ATA) and the American Association of Clinical Endocrinologists (AACE) recommend a multimodality approach for treating thyroid storm that includes taking five drops of a saturated solution of potassium iodine every 6 hours (15,92699).
• Thyroid nodules. Combining oral iodine with thyroxine seems to improve the resolution of thyroid nodules. Details: A clinical study in patients with benign nodular thyroid disease and possible iodine deficiency shows that taking iodized salt 200 mcg daily in addition to thyroxine 1.5 mcg/kg daily after surgery seems to reduce the size of the thyroid remnant by 40%, compared with a 10% reduction in patients given thyroxine alone (55927). Also, one large clinical trial in patients with nodular goiter shows that taking potassium iodide 150 mcg daily in combination with levothyroxine 50-100 mcg daily for 12 months reduces nodule volume by about 17%, compared with 7% in the group using levothyroxine alone (91392).
• Venous leg ulcers. Topical cadexomer iodine seems to improve the healing of venous leg ulcers; however, it is unclear if applying povidone-iodine is beneficial. Details: A meta-analysis of four small clinical studies in patients with venous leg ulcers shows that applying cadexomer iodine results in complete healing of ulcers in 33% of patients after 4-12 weeks, compared with only 15% of patients receiving standard care alone. However, use of cadexomer iodine was associated with more adverse effects than standard care. Furthermore, preliminary clinical research shows that applying cadexomer iodine is comparable to hydrocolloid dressing, paraffin gauze dressing, dextranomer, and silver-impregnated dressings for improving the rate of complete healing. A meta-analysis of preliminary clinical research show that povidone-iodine has comparable healing rates when compared with amoxicillin, hydrocolloid dressings, and moist or foam dressings (99798). These findings were consistent with an older version of this meta-analysis (56076).

POSSIBLY INEFFECTIVE

• Catheter-related infections. Topical povidone-iodine seems to be less effective than chlorhexidine for preventing infections from intravascular catheters. Furthermore, it does not seem to reduce the risk of catheter-related urinary tract infections. Details: One meta-analysis of clinical research shows that topical application of povidone-iodine reduces the risk of bloodstream infections when applied at the insertion site of hemodialysis central venous catheters (55883). However, disinfecting catheter insertion sites using povidone-iodine seems to be less effective for preventing blood stream infections in patients receiving central venous, pulmonary artery, or peripheral artery catheters when compared with chlorhexidine solutions (55883,55916). In addition, periurethral cleansing with povidone-iodine 10% prior to bladder catheterization, as well as bladder irrigation with povidone-iodine 2% prior to urinary catheter removal, does not seem to reduce the risk of urinary tract infections when compared with placebo (56058,56126).
• Prematurity. Maternal iodine supplementation does not seem to impact neurological development in premature infants. Details: A meta-analysis of two clinical trials in premature infants shows that adding iodine to enteral or parenteral feeds does not improve mental, visual, or auditory development or reduce the risk of death when compared with no iodine supplementation (99797).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Chyluria. It is unclear if topical iodine is beneficial in patients with chyluria. Details: A small clinical study in patients with chyluria suggests that using povidone-iodine 0.2% solution as a sclerosant in renal pelvic instillation sclerotherapy (RPIS) may be as effective as using silver nitrate 1% (55970).
• Corneal ulceration. It is unclear if topical iodine is beneficial in patients with corneal ulceration. Details: Preliminary clinical research shows that administering povidone-iodine 2.5% eye drops every two hours for two weeks in addition to standard antibiotic therapy does not reduce visual impairment in patients with corneal ulcers when compared with standard antibiotic therapy alone (55971).
• Coronavirus disease 2019 (COVID-19). It is unclear if rinsing with a povidone-iodine mouthwash and using a povidone-iodine nasal spray and ointment can reduce the spread of COVID-19. Details: A small clinical study in adults with PCR-confirmed COVID-19 shows that orally swishing and gargling 25 mL of povidone-iodine (PI) 1% solution, then, into each nostril, spraying 2.5 mL of PI 1% solution and applying one dab of PI 10% ointment, and repeating this 4 times daily for 5 days does not seem to alter the quantity of viral RNA over time when compared with control (105877). The validity of this finding is limited because all study participants achieved negative viral titers on the third day of the study.
• Cutaneous sporotrichosis. It is unclear if topical iodine is beneficial in patients with cutaneous sporotrichosis; research is conflicting. Details: Anecdotal reports and case series suggest that taking saturated solution of potassium iodide (SSKI) orally is effective for most patients when used alone or in combination with another antifungal, including terbinafine or itraconazole (17562,17563,17564,17565,17566,17567,17568,17569,17570,17571) (17572,17573). In one non-controlled clinical study, treatment with SSKI, starting with 3 drops (150 mg potassium iodide) daily and titrating up, resulted in symptom resolution in about 90% of patients after about 33 days of treatment (17561). However, some patients are not able to take SSKI due to intolerable side effects (17561,17572).
• Hyperthyroidism. It is unclear if oral potassium iodide is beneficial for patients with Graves' disease undergoing total thyroidectomy. Details: A retrospective study in patients with Graves' disease undergoing total thyroidectomy shows that preoperative administration of saturated solution of potassium iodide (SSKI) 5% does not reduce the rate of postoperative complications, such as transient or permanent hypoparathyroidism, transient recurrent laryngeal nerve (RLN) palsy, definitive RLN palsy, and cervical hematoma, when compared with no preoperative administration (108707).
• Infant development. It is unclear if maternal iodine supplementation impacts neurological development in infants. Details: Three-year follow-up data from a clinical study in infants and breastfeeding females shows that maternal supplementation of iodine 150 mcg daily improves child cognitive scores, but does not affect language or motor scores, when compared with placebo. Supplementation with a higher dose of 300 mcg daily yielded similar cognitive, language, and motor scores as the 150 mcg dose (108706). This finding aligns with the daily recommended dietary allowance (RDA) of 290 mcg during lactation, which is sometimes achieved by augmenting the diet with a 150-mcg iodine supplement (7135).
• Postoperative bleeding. It is unclear if topical iodine is beneficial in patients with postoperative bleeding. Details: A small clinical study suggests that irrigating extraction sockets with povidone-iodine 1% stops bleeding in a greater number of patients following tooth extraction when compared with a saline solution (56011).
• Rhinosinusitis. It is unclear if topical iodine is beneficial in patients with rhinosinusitis. Details: A small prospective cohort study in patients with recalcitrant chronic rhinosinusitis has found that using a povidone-iodine 0.08% nasal rinse every other day for 7 weeks in addition to standard therapy improves symptoms and reduces signs of infection when compared with baseline (103074). However, one small clinical study in patients with a history of sinus surgery and acute exacerbations of chronic sinusitis shows that receiving povidone-iodine nasal irrigations twice daily for 30 days is no different than irrigations with mupirocin or normal saline for improving nasal symptoms. However, mupirocin tended to reduce bacteria count to a greater extent than the povidone-iodine solution (105878). This finding is limited due to small study size and potential lack of power to detect differences between groups.
• Thyroid cancer. It is unclear if dietary iodine is associated with complications in patients with papillary thyroid cancer. Details: A retrospective study in patients in China with papillary thyroid cancer has found that dietary intake of iodine resulting in serum concentrations greater than 90 mcg/L is associated with a 75% increased risk of cervical lymph node metastases when compared with concentrations less than 45 mcg/L (108708). Actual dietary intake of iodine was not reported, limiting the validity of this finding.
• Ventilator-associated pneumonia (VAP). It is unclear if oral iodine rinse is beneficial for the prevention of VAP. Details: A small clinical study in patients with severe head trauma suggests that regularly rinsing the throat with 20 mL of povidone-iodine 10% solution decreases the risk for VAP when compared with using a saline rinse (56003).
• Wound healing. It is unclear if topical iodine is beneficial for wound healing. Details: A meta-analysis of clinical research shows that topical iodine, as cadexomer iodine or povidone-iodine, is superior to non-antiseptic dressings and some antiseptic agents, such as silver sulfadiazine, for reducing wound size. However, iodine seems to be less effective than local antibiotics such as rifamycin (56083). More evidence is needed to rate iodine for these uses.

(Read more about IODINE)

LIKELY EFFECTIVE

• Selenium deficiency. Oral selenium is effective for the treatment and prevention of selenium deficiency. Details: Selenium supplementation is effective for reversing symptoms of selenium deficiency, as well as for preventing the development of selenium deficiency (4844,90357).

POSSIBLY EFFECTIVE

• Autoimmune thyroiditis. Oral selenium seems to improve autoimmune thyroiditis in adults, but the evidence of benefit in children is conflicting. Details: A meta-analysis of mostly small, low-quality clinical and observational studies in children and adults with Hashimoto thyroiditis shows that taking selenium 83 mcg, selenomethionine 50 mcg or 200 mcg, or selenium 83 mcg with myoinositol 600 mg daily for 3 to 6 months reduces thyroid peroxidase antibody (TPOAb) levels and thyroglobulin antibody (TgAb) levels after 6 months of treatment when compared with baseline or placebo. However, there was no change in thyroid antibody levels at 3 months, suggesting a longer duration of 6 months is needed to sufficiently reduce serum antibody levels. Additionally, subgroup analysis suggests that patients with higher baseline thyroid antibody levels might benefit more from selenium supplementation compared to those with lower baseline thyroid antibody levels (113645). The validity of these effects is limited by high heterogeneity between baseline thyroid antibody levels amongst the included studies. Additionally, clinical research in adults with thyroiditis shows that taking selenium up to 200 mcg daily in combination with levothyroxine reduces TPOAbs by about 6% to 30% more than placebo after 3-12 months of treatment (9797,17510,17511,17512,17513,17515,17516,97943,104424). Selenium also seems to improve measures of quality of life such as feelings of well-being and mood (17515). Doses under 200 mcg daily might not be as effective (17512); selenomethionine might be more effective than sodium selenite (97943). Some research shows that selenium might be more effective in patients with more severe disease activity and less effective in patients with only moderate disease activity (9797,17513,17515). Also, selenium might not reduce TPOAbs in patients newly diagnosed with thyroiditis not receiving concurrent levothyroxine (97943). There is no reliable evidence about the effect of selenium on thyroid function or thyroid morphology. Despite positive findings in adults, most clinical research in children suggests that taking selenium 50-200 mcg daily for 3-12 months does not significantly improve TPOAb, TgAb, or thyroid echogenicity (17514,90362).
• Kashin-Beck disease. Selenium seems to help prevent Kashin-Beck disease, but does not improve symptoms in patients with existing disease. Details: A meta-analysis of prospective studies conducted in China shows that adding salt enriched with selenium to the diet of healthy children for up to 4 years reduces the odds of developing Kashin-Beck disease by 84% when compared with the use of iodine salt. Additionally, in children with Kashin-Beck disease, adding salt enriched with selenium to the diet might help heal metaphyseal lesions (97945). However, selenium does not seem to improve symptoms in those with existing disease. A clinical trial in children with Kashin-Beck disease shows that selenium supplementation does not improve joint pain or mobility when compared with placebo (55941).
• Pre-eclampsia. Oral selenium might reduce the risk of pre-eclampsia in pregnant patients. Details: A meta-analysis of three low-quality clinical trials in pregnant patients shows that taking selenium 60-100 mcg daily for up to 6 months reduces the risk of pre-eclampsia by 72% when compared with placebo. Additionally, a meta-analysis of population research has found that the risk of pre-eclampsia is higher in pregnant patients with low selenium levels. Selenium levels were about 6.5 mcg/L lower in those who developed pre-eclampsia compared with those who did not (97946).

POSSIBLY INEFFECTIVE

• Asthma. Oral selenium does not seem to improve asthma symptoms. Details: Epidemiological research has found that plasma selenium concentration is not associated with asthma (74422). Also, clinical research in patients with asthma shows that taking selenium 100 mcg daily for 14-24 weeks does not improve symptoms, lung function, use of rescue inhalers, or quality of life when compared with placebo (74490,74387).
• Atopic dermatitis (eczema). Oral selenium-enriched yeast does not seem to improve eczema symptoms. Details: A small clinical study in patients with eczema shows that taking selenium-enriched yeast 600 mcg daily for 12 weeks, either alone or in combination with vitamin E 600 IU daily, does not improve symptom severity when compared with placebo (74456).
• Cardiovascular disease (CVD). Most research shows that oral selenium does not reduce the risk of CVD. Details: Meta-analyses of clinical trials in patients with and without risk factors for CVD show that taking selenium alone or with other supplements for up to 8 years does not reduce the risk of CVD mortality or fatal and non-fatal CVD events (90360,97078). When reported, patients in these studies all had adequate plasma selenium levels at baseline (90360).
• Colorectal cancer. Oral selenium does not seem to prevent cancer of the colon and rectum. Details: Epidemiological research has found no association between serum concentrations of selenium and the risk of developing colorectal cancer (74321,97085). Also, meta-analyses of clinical research, as well as individual clinical trials, show that taking selenium 100-200 mcg daily, alone or in combination with other vitamins and minerals, does not reduce the risk of colorectal cancer when compared with control (16707,34676,90361,97092).
• Dyslipidemia. Most research shows that oral selenium supplementation does not improve cholesterol levels. Details: A meta-analysis of 11 clinical studies in adults with dyslipidemia shows that taking selenium 50-300 mcg daily for 8-24 weeks does not increase high-density lipoprotein (HDL) cholesterol levels or decrease total or low-density lipoprotein (LDL) cholesterol levels when compared with placebo. Taking selenium might modestly improve triglyceride levels, but this improvement is unlikely to be considered clinically significant (99662). Another meta-analysis of 21 mostly small, low-quality clinical studies, some of which were included in the prior meta-analysis, shows that taking various forms of selenium may modestly decrease total cholesterol levels, but does not improve triglycerides, LDL, or HDL cholesterol when compared with placebo (110595). However, the validity of the findings from this meta-analysis is limited by the heterogeneity of the included studies, which assessed various selenium dosing regimens and enrolled healthy patients or those with various cardiovascular and non-cardiovascular conditions.
• Low birth weight. Oral or intravenous selenium supplementation does not improve outcomes in low birth weight infants. Details: Low selenium levels have been documented in low birth weight infants. However, selenium supplementation, orally or intravenously, does not appear to improve most outcomes in low birth weight infants. Clinical research shows that administering selenium, either as 7-10 mcg/kg daily parenterally or 5 mcg/kg daily orally, does not improve oxygen dependency or reduce the risk of death in low birth weight infants when compared with placebo. However, supplementation decreases the incidence of sepsis by up to 33% (74288,97083).
• Lung cancer. Oral selenium does not reduce lung cancer risk in most patients. Details: While a large cohort study suggests that increased dietary intake of selenium is associated with a lower risk of lung cancer, supplemental selenium does not appear to have the same effect. Additionally, a meta-analysis of three large clinical trials of over 20,000 patients, including patients with resected stage I non-small-cell lung cancer, shows that taking selenium 200-400 mcg daily for up to 5 years does not reduce the risk of lung cancer when compared with control (92912,97092). A secondary analysis of one of these studies found that selenium supplementation might reduce lung cancer risk in people with selenium levels below 105 ng/mL (9798). Also, a large study in healthy Chinese patients shows no benefit of using selenium in combination with other nutrients for over 5 years when compared with control (34539).
• Nonmelanoma skin cancer. Oral selenium does not reduce the risk of nonmelanoma skin cancer and has been linked to increased risk in some patients. Details: Epidemiological research has found that higher selenium intake is not associated with a reduced risk of nonmelanoma skin cancer (97085). Furthermore, clinical research shows that taking selenium orally 200 mcg daily does not reduce the risk of basal cell carcinoma when compared with control (2664,10687). In addition, some evidence shows that daily selenium supplementation might increase the risk of squamous cell carcinoma and total non-melanoma skin cancer (10687).
• Prostate cancer. Oral selenium does not seem to reduce prostate cancer risk. Details: Population studies have found that higher serum or toenail selenium levels are associated with a decreased risk of prostate cancer (8734,8735,8736,92911,10263). However, clinical research does not support this finding. A meta-analysis of 5 large clinical trials of over 20,000 patients shows that selenium 200-400 mcg daily for up to 5 years does not reduce the risk of prostate cancer when compared with control (97092). A 7-14 year follow-up study of one of these trials shows there was still no reduction of prostate cancer risk (17688). Selenium has also shown no benefit when used in combination with other supplements. In a large-scale clinical study (SU.VI.MAX), taking selenium 100 mcg in combination with vitamin C, vitamin E, beta-carotene, and zinc did not reduce prostate cancer risk (14135). In 2009, the US Food and Drug Administration (FDA) approved a qualified health claim regarding selenium and prostate cancer risk, stating that it is highly unlikely that selenium supplements reduce the risk of prostate cancer (102373).
• Psoriasis. Oral selenium does not seem to reduce psoriasis severity. Details: Clinical research shows that taking selenium-enriched yeast 600 mcg daily for 12 weeks, either alone or in combination with vitamin E 600 IU daily, does not reduce the severity of psoriasis when compared with placebo (74460).
• Sepsis. Intravenous selenium does not appear to improve outcomes in septic adults. Details: Earlier meta-analyses of clinical trials in septic adults showed that parenteral administration of selenium, along with routine nutritional interventions, reduces the risk of mortality by 11% to 27% when compared with placebo (90347,92907,92910). However, a more recent meta-analysis, which includes a large, multi-center study of over 1000 cases, shows that parenteral selenium does not reduce mortality in septic adults at 28, 90, or 180 days when compared with placebo (99658). Enteral selenium with other nutrients has been studied for sepsis in children. Clinical research in children shows that taking enteral selenium 40-400 mcg daily with zinc, glutamine, and IV metoclopramide is no more effective than whey protein for reducing time to first episode of nosocomial infection or sepsis in the intensive care unit (ICU). However, the selenium combination treatment might reduce the risk for sepsis in immunocompromised pediatric patients (86095).

LIKELY INEFFECTIVE

• Bladder cancer. Despite promising initial research, oral selenium does not seem to prevent the development, recurrence, or progression of bladder cancer. Details: In 2009, the US Food and Drug Administration (FDA) approved a qualified health claim regarding selenium and bladder cancer risk based on two small studies. However, the FDA determined that it is highly uncertain that selenium supplements reduce the risk of bladder cancer (102373). Since then, most available research has not confirmed an association between selenium and bladder cancer risk. Epidemiological and clinical research suggests that selenium supplementation is not associated with a reduced risk of bladder cancer and does not prevent recurrence, slow progression, or improve overall survival in patients with bladder cancer (97085). One moderate-sized clinical study shows that taking selenium 200 mcg daily with or without vitamin E 200-400 IU daily for 7 years does not prevent bladder cancer in older males (90352). Another small clinical study shows that taking selenium yeast 200 mcg daily for 3 years does not prevent the recurrence of bladder cancer when compared with placebo in patients that had undergone a transurethral resection for non-invasive bladder cancer (97087). These findings are supported by another moderate-sized clinical study in adults with non-invasive bladder cancer which shows that taking selenium 200 mcg with or without vitamin E 200 IU daily for a median of 1.5 years does not prevent recurrence, slow bladder cancer progression, or improve overall survival when compared with placebo over a median follow-up period of 5.5 years (114116).
• Diabetes. Increased intake of selenium, either in the diet or as a supplement, is associated with an increased risk for developing type 2 diabetes. It is unclear if oral selenium is beneficial in patients with type 2 diabetes. Details: Observational research suggests that high serum selenium levels, high dietary selenium intake, and selenium supplementation are each linked to an increased risk of developing diabetes (97091,99661). Consuming more than the recommended dietary allowance (RDA) of selenium daily is associated with an increased risk of developing diabetes when compared with consuming less than the RDA (99661). However, the effect of short-term selenium supplementation in patients with diabetes is unclear. Two meta-analyses of clinical studies in adults with various health conditions show that taking supplemental selenium as selenium yeast, sodium selenite, or selenomethionine in doses of 100-960 mcg daily for 4 to 96 weeks reduces serum and fasting insulin levels and increases measures of insulin sensitivity but does not lower fasting blood glucose or glycated hemoglobin (HbA1c) when compared with placebo. Additionally, selenium supplementation does not reduce total or low-density lipoprotein (LDL) cholesterol or triglycerides but may improve high-density lipoprotein (HDL) cholesterol (110593). However, the validity of the findings from the meta-analyses is limited by the heterogeneity of the included studies, which enrolled healthy adults and patients with diabetes, gestational diabetes, cardiovascular disease, heart failure, obesity, polycystic ovary syndrome (PCOS), cancer, and Alzheimer disease.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral selenium reduces the risk of cognitive decline in older adults. Details: A cross-sectional study in elderly Americans has found that lower blood levels of selenium are associated with a greater risk of poor cognitive scores when compared with higher levels (104426).
• Alcohol-related liver disease. Although there is interest in using oral selenium for alcohol-related liver disease, there is insufficient reliable information about the clinical effects of selenium for this condition.
• Allergic rhinitis (hay fever). Although there is interest in using oral selenium for allergic rhinitis, there is insufficient reliable information about the clinical effects of selenium for this condition.
• Alzheimer disease. Oral selenium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with Alzheimer disease shows that taking selenium 200 mcg with a probiotic daily for 12 weeks improves cognitive function as measured by the Mini-Mental State Examination (MMSE) when compared with placebo. However, when selenium 200 mcg was taken alone, no improvement in cognitive function over placebo was found, so it is unclear whether the improvements in cognitive function are due to the probiotics or the combination of ingredients (113659). Another very small clinical study in adults with mild-to-moderate Alzheimer disease shows that taking supranutritional selenium 30 mg daily for 12 weeks does not change cognitive measures, cerebrospinal fluid biomarkers, or neuroimaging biomarkers of Alzheimer disease progression when compared with placebo or nutritional selenium doses. However, the control group showed worsened diffusivity imaging markers indicative of deterioration of axonal structure integrity, while no such decline was noted in supranutritional selenium neuroimaging (113660).
• Androgenic alopecia. Oral selenium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults with androgenic alopecia or telogen effluvium shows that taking a combination product containing selenium, hydrolyzed collagen, taurine, cysteine, methionine, and iron (GFM Oral, Cantabria Labs) daily for 12 weeks daily along with conventional therapy, consisting primarily of finasteride or minoxidil, improves hair loss when compared with conventional therapy alone (111636). It is unclear if this effect is due to selenium, other ingredients, or the combination.
• Arsenic poisoning. It is unclear if oral selenized yeast is beneficial for patients that were exposed to high levels of arsenic in the environment. Details: A small clinical study in Chinese people environmentally exposed to high concentrations of arsenic shows that taking selenized yeast providing 100-200 mcg of selenium daily for 14 months decreases the concentration of arsenic and symptoms of toxicity when compared with placebo (7831).
• Benign prostatic hyperplasia (BPH). Oral selenium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in men with BPH shows that taking selenium 240 mcg plus silymarin 570 mg daily for 6 months reduces lower urinary tract symptoms when compared with placebo (88155). Another clinical study in men with BPH shows that taking tamsulosin 0.4 mg plus a specific product containing selenium, saw palmetto, and lycopene (Profluss, Ayanda AS) daily for one year improves lower urinary tract symptoms and urodynamic parameters when compared with tamsulosin-alone (90354). It is unclear if these effects are due to selenium, other ingredients, or the combinations.
• Burns. Oral selenium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Small clinical studies in patients with burns on 46% of their body surface suggest that taking a combination of copper 2.5-3.1 mg, selenium 315-380 mcg, and zinc 26.2-31.4 mg daily reduces the incidence of hospital-acquired pneumonia, but does not seem to improve wound healing, hospital stay, or mortality, when compared with placebo (6520,74382). Another very small clinical study in burn patients suggests that taking copper 4.5 mg, selenium 190 mcg, and zinc 40 mg daily reduces the duration of hospitalization, but does not have an effect on recovery and wound treatment requirements, when compared with standard dietary doses of these nutrients (74485).
• Cancer. Selenium does not seem to reduce the risk of cancer in most people, but it might be beneficial in those with low selenium levels and in men. Details: Meta-analyses of clinical research and several clinical studies show that selenium supplementation does not reduce the incidence of cancer or cancer-related mortality when compared with control (14109,34538,74414,97078,97092). In clinical studies, selenium 100-400 mcg taken daily for 2-7.5 years with or without additional antioxidants did not reduce overall cancer risk (14109,34538,74414). However, most evidence did not assess baseline selenium levels. Other evidence suggests that selenium may have a benefit in men and in people with lower selenium levels. Epidemiological research has found that selenium intake at the recommended daily allowance (RDA) of 55 mcg or higher is associated with decreased cancer incidence and cancer mortality, especially in men (97085,103164). However, this research suggests that cancer risk was also influenced by age, body mass index, and smoking status (103164). Some clinical research also suggests that taking selenium might decrease the risk of cancer, when only men are considered (14109). An older meta-analysis of clinical research suggests that selenium was particularly beneficial in patients with lower baseline levels of selenium and in patients at high risk for cancer (90350). In 2003, the US Food and Drug Administration (FDA) approved a qualified health claim stating that consumption of selenium may produce anticarcinogenic effects and reduce the risk for certain forms of cancer. However, the FDA has determined that the evidence is limited and inconclusive (102374).
• Cataracts. Oral selenium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: An ancillary clinical study shows that taking selenium 200 mcg daily with or without vitamin E 400 IU daily for around 5.6 years does not reduce the risk of age-related cataracts in men when compared with placebo (92902).
• Cervical dysplasia. It is unclear if oral selenized yeast is beneficial for patients with cervical dysplasia of mild severity. Details: A small clinical study in patients with cervical intraepithelial neoplasia grade 1 (CIN1) shows that taking yeast containing selenium 200 mcg daily for 6 months resulted in regression of CIN1 in 88% of participants, compared with regression in only 55% of participants taking placebo (97944).
• Chemotherapy-induced nephrotoxicity. Oral selenium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in cancer patients shows that drinking a beverage containing vitamin C, vitamin E, and selenium does not prevent cisplatin-induced nephrotoxicity when compared with a placebo beverage (74340). However, poor compliance to treatment may limit the validity of these findings.
• Chronic fatigue syndrome (CFS). Although there is interest in using oral selenium for CFS, there is insufficient reliable information about the clinical effects of selenium for this condition.
• Cirrhosis. Oral selenium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with primary biliary cirrhosis shows that taking a combination of selenium, vitamin A, vitamin C, vitamin E, methionine, and coenzyme Q10 for 12 weeks does not improve fatigue or any other disease-related symptoms when compared with placebo (34494).
• Cisplatin-associated ototoxicity. Oral selenium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in cancer patients shows that drinking a beverage containing vitamin C, vitamin E, and selenium does not prevent cisplatin-associated hearing loss when compared with placebo beverage (74340). However, poor compliance to treatment may limit the validity of these findings.
• Colorectal adenoma. It is unclear if oral selenium prevents recurrence of adenomas in the colon and rectum. Details: A large clinical study in patients with a history of colorectal adenomas shows that taking a specific selenium supplement (SelenoExcell High Selenium Yeast, Cypress Systems) 200 mcg daily for about 33 months does not reduce adenoma recurrence when compared with placebo. However, in a sub-group of patients with advanced adenomas at baseline, selenium seems to reduce risk of recurrence by 18% when compared with placebo (97091). Some research also shows that taking selenium in combination with zinc, and vitamins A, C, and E reduces adenoma recurrence when compared with placebo (92903). It is not clear any benefit is due to selenium, other nutrients, or the combination.
• Congestive heart failure (CHF). Oral selenium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in elderly patients with heart failure living in Sweden shows that taking a specific selenium supplement (SelenoPrecise, Pharma Nord) 200 mcg plus a specific coenzyme Q10 supplement (Bio-Quinon, Pharma Nord) 200 mg daily for about 4 years reduces the risk of cardiovascular mortality by about 55% when compared with placebo (92904). The risk reduction seems to be most pronounced in patients with lower selenium levels (97906). Furthermore, at 10- and 12-year follow-ups, cardiovascular mortality in the treatment group continued to be 49% and 41% lower, respectively, when compared with placebo (96546,97466). It is unclear if the benefit can be attributed to selenium, coenzyme Q10, or the combination.
• Coronary artery bypass graft (CABG) surgery. It is unclear if oral selenized yeast is beneficial for patients undergoing CABG surgery. Details: A small clinical study in patients undergoing CABG surgery shows that taking selenium 200 mcg daily as selenium yeast for 4 weeks improves glycemic control, lipid levels, and markers of inflammation when compared with placebo (103163). It is not known whether this influences the outcome or complications of CABG surgery.
• Critical illness (trauma). Evidence on the use of intravenous selenium in critically ill patients is conflicting. Details: The most recent meta-analysis of 24 clinical trials in critically ill patients shows that intravenous selenium does not improve survival over 6 months, shorten hospital stay, or reduce intensive care unit (ICU) stay, infectious complications, development of acute kidney failure, or duration of mechanical ventilation when compared with control. Also, length of ICU stay was increased by about 4.5-fold in patients receiving selenium in doses of more than 1000 mcg daily (109086). These findings are similar to those of a meta-analysis of 21 randomized controlled trials in critically ill patients from 2016 which shows that intravenous selenium given alone or with other nutrients does not improve mortality, duration of hospital stay, or kidney function when compared with control (97090). However, another recent meta-analysis of 19 clinical trials in critically ill patients shows that intravenous selenium reduces total mortality by 14% and shortens hospital stay by about 2 days when compared with control, without affecting ICU stay, duration of mechanical ventilation, or mortality over 28 days (101345). The reasons for these discrepancies are not clear and do not seem to be completely explained by differences in doses or durations of selenium (109086). Some reasons for the discrepancies might include differing analytic methods used in meta-analyses, as well as variations in forms of selenium, concomitant treatments, and specific patient populations. One sub-analysis shows that, when limited to randomized controlled trials examining the effect of selenium supplementation in patients sustaining traumatic injury, the odds of mortality was reduced by about 26% and duration of ICU and hospital stay were modestly reduced. There was no effect on infectious complications (109090).
• Dementia. It is unclear if oral selenium prevents dementia or reduces symptoms. Details: Observational research has found that taking selenium 200 mcg daily for 4 years does not decrease the incidence of dementia in men 60 years or older (93570). However, the follow-up period may not have been long enough to reliably detect the effect of selenium on the development of dementia. Also, the screening method used to detect new cases of dementia may have failed to identify individuals presenting with only the initial symptomatic stages of the disease (93570,93571).
• Depression. It is unclear if oral selenium is beneficial for the treatment of prevention of depression. Details: A meta-analysis of observational research has found no difference in serum levels of selenium between patients with or without depression. In addition, serum levels of selenium do not correlate with depression scores (109091). A meta-analysis of clinical research shows that selenium supplementation, usually 100-200 mcg daily, modestly reduces symptoms of depression; however, at least one of the three studies included in this meta-analysis investigated the effects of selenium in patients with postpartum depression, specifically (109091). These meta-analyses are limited by the quality of included research and the small number of available studies.
• Diabetic nephropathy. It is unclear if oral selenium alleviates diabetic nephropathy symptoms. Details: A small clinical study in patients with diabetic nephropathy shows that taking selenium (Nature Made) 200 mcg daily for 12 weeks does not improve kidney markers such as blood urea nitrogen or serum creatinine when compared with placebo (97084).
• Dilated cardiomyopathy. There is limited evidence on the oral use of selenium in patients with Keshan disease and peripartum cardiomyopathy. Details: Observational research in patients with a specific type of dilated cardiomyopathy called Keshan disease and congestive heart failure has found that selenium supplementation is associated with a 61% decreased risk of cardiac death when compared with no supplementation (101346). A small clinical study in patients with peripartum cardiomyopathy and selenium deficiency shows that taking selenium 200 mcg daily for 3 months does not seem to improve heart failure symptoms or left ventricle systolic function, or prevent death, when compared with no treatment (104420).
• Esophageal cancer. Limited research suggests that oral selenium does not reduce esophageal cancer risk. Details: Low quality clinical research suggests that taking selenium supplements alone or with other vitamins does not decrease the risk of esophageal cancer when compared with control (4679,12185).
• Gastric cancer. Oral selenium has only been evaluated in combination with other ingredients and in a specific patient population; its effect when used alone and in other populations is unclear. Details: Population research in Chinese patients has found that high levels of selenium are associated with lower risk of gastric cancer and cancer mortality (97948). However, clinical research does not agree. A large clinical study in patients residing in China shows that taking selenium 37.5 mcg in combination with vitamin C 250 mg and vitamin E 100 IU twice daily for about 7.3 years does not reduce the risk of developing gastric cancer or precancerous gastric lesions when compared with placebo. This combination treatment was not associated with reduced gastric cancer incidence or mortality at the 14-year follow-up of this study (14447,51470). Another clinical study in healthy Chinese adults also shows that taking a combination of selenium 50 mcg, vitamin E 30 mg, and beta-carotene 15 mg daily for 5.2 years does not reduce the risk of gastric cancer when compared with control (4679). It is unclear if these findings are generalizable to populations in geographic locations other than China.
• Graves' ophthalmopathy. It is unclear if oral selenium is beneficial for Graves' ophthalmopathy. Details: A small clinical trial in adults with Graves' ophthalmopathy shows that taking selenium 100 mcg twice daily for 6 months is modestly beneficial for reducing disease activity, based on signs and symptoms including pain, swelling, and redness, when compared with placebo (109085).
• Hepatitis C. Oral selenium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with hepatitis C shows that taking a combination of selenium 200 mcg, vitamin C 500 mcg, and vitamin E 945 IU daily for 6 months does not have an effect on levels of alanine aminotransferase or viral load when compared with placebo (74377).
• HIV/AIDS. It is unclear if oral selenium improves outcomes in patients with HIV. Details: Clinical trials in HIV-positive men and women, most receiving anti-retroviral therapy (ART), shows that taking selenium 200 mcg daily for up to 2 years can reduce HIV-1 viral load, increase CD4 cell counts, and lower the risk of hospitalizations when compared with placebo (15266,74314). However, not all research agrees. Two small clinical trials in HIV-positive patients taking ART shows that taking selenium 100-200 mcg daily for 6-12 months does not reduce the risk for opportunistic infections and does not increase CD4 counts when compared with control (7830,104417). Furthermore, selenium does not seem to benefit patients that are not receiving conventional ART. A large clinical study in HIV-infected pregnant patients in Tanzania with poor access to ART shows that taking selenium 200 mcg daily with prenatal vitamins until 6 months after delivery, does not improve progression of HIV nor pregnancy outcomes when compared with no selenium supplementation (74419). Another large clinical study in HIV-infected and ART-naïve patients in Botswana shows that taking selenium 200 mcg daily for 24 months does not slow HIV progression when compared with placebo (92905).
• Hypertension. It is unclear if oral selenium improves blood pressure. Some evidence suggests selenium supplementation may slightly increase systolic blood pressure. Details: A meta-analysis of 5 small clinical studies in adults with various health conditions shows that taking selenium or selenium yeast 100-200 mcg/day for 6-12 weeks may increase systolic blood pressure by about 2 mmHg but does not impact diastolic blood pressure when compared with placebo (110595). However, the validity of the findings from this meta-analysis is limited by the heterogeneity of the included studies, which enrolled patients with preeclampsia, gestational diabetes, obesity, or heart failure. Additionally, all studies were conducted in Iran; it is unclear if these findings are generalizable to populations in other geographic locations.
• Hyperthyroidism. It is unclear if oral selenium alleviates symptoms in patients with Graves' disease. Details: A small clinical study in patients with Graves' hyperthyroidism shows that taking sodium selenite 300 mcg daily in addition to treatment with methimazole for 24 weeks does not affect symptoms or recurrence rates when compared with placebo plus methimazole (97089). Oral selenium has also been studied in combination with other supplements. A small preliminary clinical trial in patients with newly diagnosed Graves' disease and low levels of selenium and vitamin D shows that taking selenium 100 mcg daily for 180 days along with vitamin D as cholecalciferol 7000 IU weekly for 270 days, in addition to methimazole, modestly reduces levels of serum free thyroxine and improves quality of life when compared with methimazole alone. However, taking selenium and vitamin D did not affect levels of free triiodothyronine or positive thyroid stimulating hormone (TSH) receptor antibody (109049).
• Hypothyroidism. It is unclear if oral selenium improves thyroid hormone balance in elderly individuals, pregnant patients, or patients with subclinical hypothyroidism. In patients with iodine deficiency, selenium supplementation may be harmful. Details: Low selenium levels or selenium deficiency seems to reduce conversion of thyroxine (T4) to triiodothyronine (T3). However, clinical research in healthy elderly patients is conflicting. Although one study shows that taking selenium 100 mcg daily for 3 months increases conversion of T4 to T3 when compared with placebo (17508), a larger study shows that taking selenium 100-300 mcg daily for 6 months does not impact conversion of T4 to T3 when compared with placebo (17509). Additionally, taking selenium can worsen hypothyroidism in people with iodine deficiency. People who are iodine- and selenium-deficient should not receive selenium supplements without concomitant iodine. In these individuals, selenium increases conversion of T4 to T3, but the thyroid gland lacks iodine to synthesize more T4 (1664,14563,14564,14565,17508). Selenium does not have a significant effect on thyroid function when iodine intake is adequate (1664,4844). In pregnant patients with hypothyroidism, clinical research shows that taking selenium does not reduce complications such as pre-eclampsia or preterm birth. However, selenium might improve postpartum thyroid function and decrease the risk of postpartum thyroiditis (17507). Also, taking selenium 200 mcg daily during pregnancy seems to reduce the risk of developing postpartum thyroid dysfunction and permanent hypothyroidism by 41% and 42%, respectively, when compared with placebo in euthyroid pregnant patients who are positive for thyroid peroxidase antibodies (74391). Selenium supplementation has also been studied for subclinical hypothyroidism. Clinical research in females aged 18 to 50 years with or at risk for subclinical hypothyroidism in Slovakia shows that taking selenium 83 mcg daily and myo-inositol 600 mg daily for 6 months modestly reduces thyroid stimulating hormone (TSH) and thyroid auto-antibody titers when compared with baseline. Selenium and myo-inositol supplementation also reduced patient-reported hypothyroid symptoms including fatigue, menstrual cycle irregularity, and intolerance to heat or cold (110591). The interpretation of these results is limited by the lack of a control group. In addition, it is unclear if these effects are due to selenium, myo-inositol, or the combination.
• Influenza. Although there is interest in using oral selenium for influenza, there is insufficient reliable information about the clinical effects of selenium for this condition.
• Kidney failure. It is unclear if oral selenium is beneficial for improving lipid parameters in patients on hemodialysis. Details: Selenium levels may be low in patients undergoing chronic hemodialysis, and supplementation might be needed (1805,11053). However, clinical research in patients on hemodialysis shows that taking selenium daily for 3 months does not improve the lipid profile when compared with taking placebo (109095).
• Lichen planus. It is unclear if topical or oral selenium alleviates oral lichen planus symptoms. Details: A small clinical study in patients with oral lichen planus shows that applying a selenium hydrogel (selenomethionine 14 mcg/gram) twice daily for 6 weeks seems to significantly reduce pain at a 12 week follow-up, but not immediately after use, when compared with applying topical corticosteroids and antifungal agents 2-4 times daily. Taking oral selenium 200 mcg twice daily for 6 weeks seems to be no different than the topical corticosteroids and antifungal treatment at both time points (104422).
• Liver cancer. It is unclear if oral selenium reduces liver cancer risk. Details: Preliminary clinical research in China suggest that taking selenium 200 mcg daily for 2-5 years can reduce the incidence of liver cancer when compared with control (74389). The benefit of selenium on prevention of liver cancer in Western countries is unknown.
• Lymphedema. It is unclear if oral selenium reduces lymphedema complications. Details: Preliminary clinical research in patients with secondary lymphedema after breast cancer surgery shows that taking a sodium selenite solution 1000 mcg daily for 1 week followed by 300 mcg daily for 2 weeks and then 200 mcg daily for a total of 15 weeks might reduce recurrence of erysipelas, a type of bacterial skin infection, when compared with placebo (15334).
• Male infertility. It is unclear if oral selenium, used alone or in combination with other antioxidants, improves pregnancy or live birth rates for couples with idiopathic male infertility. Details: Meta-analyses of 2-3 clinical trials in males with infertility show that taking selenium, alone or in combination with other antioxidants, for 12-26 weeks modestly improves sperm count and motility, but does not improve sperm morphology, when compared with placebo. Pregnancy rates and live birth rates were only studied in one clinical trial each, with no statistical evidence of benefit (109094,111459). However, the included studies may have been inadequately powered to detect a difference between groups. Studies included in the analysis used selenium 26-200 mcg daily for 3-26 weeks, either alone or in combination with vitamin A 1 mg, vitamin C 10 mg, and vitamin E 15 mg; vitamin E 400 IU and folic acid 5 mg; lycopene 6 mg, vitamin E 400 IU, vitamin C 100 mg, zinc 25 mg, folate 0.5 mg, and garlic 1000 mg; or N-acetyl-cysteine 600 mg (74526,74493,102968,109094,111459). Selenium has also been evaluated in combination with other ingredients. A retrospective study in adult males with idiopathic and varicocele-related infertility suggests that taking a combination product containing selenium 50 mcg, vitamin B12, L-carnitine, acetyl L-carnitine, citric acid, coenzyme Q10, vitamin C, zinc, and folic acid (Proxeed Plus, AltaSigma) twice daily for 6 months is associated with improvements in ejaculate volume, sperm count, sperm concentration, total motility, and progressive motility when compared to baseline. However, improvements in sperm morphology were lacking. Furthermore, patients with more severe varicocele seem to benefit most (111296). The validity of these findings is limited by a lack of comparator group. Further, it is unclear if these effects are due to selenium, other ingredients, or the combination.
• Mercury toxicity. It is unclear if oral selenium improves clearance of mercury and reduces symptoms of toxicity. Details: A small clinical trial in Chinese adults environmentally exposed to high concentrations of mercury shows that taking selenium-enriched yeast, containing selenium 100 mcg, daily for 3 months increases urinary excretion of mercury when compared with control (90351).
• Muscular dystrophy. There is limited evidence on the oral use of selenium in Duchenne muscular dystrophy. Details: Preliminary clinical research suggests that supplementation with sodium selenite 1 mg daily for 6 months does not improve disease activity in patients with muscular dystrophy (74455).
• Obesity. It is unclear if oral selenium is beneficial for weight reduction. Details: A small clinical study in adults with obesity shows that taking selenium 240 mcg daily and following a low-calorie diet for 3 months does not reduce body weight when compared with following a low-calorie diet alone (104416). Additionally, a very small clinical study in adults with overweight or obesity shows that taking L-selenomethionine 200 mcg and zinc gluconate 25 mg once daily for 8 weeks does not improve body mass index (BMI), total body fat, or fat free mass when compared with placebo (111448).
• Oral mucositis. It is unclear if oral selenium is beneficial for reducing oral mucositis in patients undergoing radiotherapy. Details: A small clinical study in patients with head and neck cancers shows that taking selenium 200 mcg twice daily for the duration of radiation therapy does not seem to reduce the incidence or severity of oral mucositis when compared with placebo (104421). It is unclear if other doses or routes of administration might be beneficial.
• Osteoarthritis. Oral selenium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with osteoarthritis shows that taking a specific selenium-containing combination supplement (Selenium-ACE) does not improve most clinical symptoms when compared with placebo (74449).
• Ovarian cancer. It is unclear if oral selenium reduces ovarian cancer risk. Details: Epidemiological research has found that there is no association between dietary selenium intake and the risk of developing ovarian cancer (74342).
• Overall mortality. Although oral selenium does not seem to reduce overall mortality risk in most patients, it might have benefit in patients with low nutrient intake. Details: Meta-analyses of clinical research show that selenium supplementation, alone or in combination with other micronutrients, does not reduce all-cause mortality when compared with placebo (15305,90360,97078). Selenium might also not be beneficial when used in combination with non-nutrient supplements. An additional large clinical study in elderly patients in Sweden shows that taking selenium 200 mcg daily plus coenzyme Q10 100 mg twice daily for around 5 years does not reduce the risk of all-cause mortality when compared with placebo. The baseline selenium status of these patients is unclear (92904). Despite these results, some evidence suggests that selenium used with other nutrients might have benefit in patients with low nutrient intake. In a large clinical study, selenium in combination with zinc, vitamin C, vitamin E, and beta-carotene lowered all-cause mortality risk in men, but not women, when compared with control (14109). Researchers speculate that this result occurred because men have a lower intake of dietary antioxidants than women. Another large clinical study in Chinese patients with chronically low nutrient intake shows that taking selenium with beta-carotene and vitamin E decreases stroke mortality, cancer mortality, and total mortality when compared with control (2673).
• Pancreatic cancer. It is unclear if oral selenium reduces pancreatic cancer risk. Details: Some epidemiological research has found that increased selenium intake is associated with a 34% lower risk of pancreatic cancer (97093). However, other observational research has found no association (101342).
• Pancreatitis. Although there is interest in using oral selenium for pancreatitis, there is insufficient reliable information about the clinical effects of selenium for this condition.
• Periodontitis. Oral selenium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with moderate or advanced periodontitis shows that taking a supplement containing selenium 30 mcg, alpha-lipoic acid, coenzyme Q10, cranberry extract, grapeseed extract, vitamin C, vitamin E, and zinc twice daily for 8 weeks in addition to standard nonsurgical therapy does not improve periodontal measures such as bleeding on probing, gingival recession, plaque index, or inflammation when compared with placebo (111708).
• Polycystic ovary syndrome (PCOS). It is unclear if oral selenium is beneficial for PCOS. Details: Most available research addressing the effects of selenium on the hormonal, metabolic, and reproductive symptoms associated with PCOS is conflicting. Meta-analyses of small clinical studies and a small clinical study in adults with PCOS show that taking selenium 200 mcg daily for 8-12 weeks might reduce total testosterone and dehydroepiandrosterone (DHEA) levels but does not seem to improve other hormone levels when compared with placebo (109096,113653,113654,113657). Additionally, a small clinical study in patients with PCOS shows that taking selenium yeast or selenium (Nature Made) 200 mcg daily for 8 weeks reduces the severity of alopecia, acne, and hirsutism when compared with placebo (109096). Research is conflicting whether selenium improves lipid profiles, glycemic indices, insulin metabolism, or anthropometric measures (109096,110596,113642,113654,113657). The effect of selenium on pregnancy outcomes in patients with PCOS who are undergoing or candidates for in vitro fertilization (IVF) is unclear. A small clinical study in patients with PCOS shows that taking selenium (Nature Made) 200 mcg daily for 8 weeks results in a significantly higher pregnancy rate of 19%, compared with 3% in those taking placebo (109096). However, another very small clinical study of the same population and dosing regimen shows that selenium does not improve IVF outcomes including pregnancy rate, endometrial thickness, number of oocytes retrieved, fertilization rate, or number of embryos when compared with placebo (113640). Selenium has also been studied in combination with other ingredients. A small clinical study in adults with PCOS shows that taking selenium 200 mcg daily for 12 weeks, along with a combination probiotic product, modestly improves subjective scores of depression, anxiety, and stress when compared with placebo. Taking this combination also modestly reduces total testosterone levels and subjective ratings of hirsutism when compared with placebo (99659). It is unclear if these effects are due to selenium, the probiotic, or the combination.
• Postoperative recovery. It is unclear if intravenous sodium selenite reduces morbidity and mortality in cardiac surgery patients. Details: A very large clinical study in adults undergoing high-risk cardiac surgery with cardiopulmonary bypass or cardioplegic arrest shows that administering intravenous high-dose sodium selenite 2000 mcg/L perioperatively, 2000 mcg/L immediately postoperatively, and then 1000 mcg/L daily in the intensive care unit (ICU) for up to 10 days does not increase the number of days alive or the number of days without persistent organ dysfunction over 30 days after surgery when compared with placebo. Additionally, intravenous sodium selenite does not reduce 30-day or 6-month mortality, intensive care unit (ICU) or hospital length of stay, or hospital readmission rates when compared with placebo (113651).
• Postpartum depression. It is unclear if oral selenium is beneficial for postpartum depression. Details: A meta-analysis of two observational studies has found that a high selenium intake is associated with a modestly reduced risk of postpartum depression. The effect of selenium supplementation on symptoms of postpartum depression is unclear. One moderate-sized clinical trial included in this publication shows that taking selenium reduces symptoms of postpartum depression (109091).
• Pregnancy-induced hypertension. It is unclear if oral selenium reduces the development of hypertension during pregnancy. Details: A small clinical study in pregnant patients shows that drinking a dietary liquid containing selenium 100 mcg daily for 6-8 weeks seems to decrease the incidence of pregnancy-induced hypertension when compared with placebo (74481).
• Premature rupture of membranes (PROM). It is unclear if oral selenium during pregnancy prevents PROM. Details: One clinical trial shows that taking selenium 100 mcg daily from the first trimester of pregnancy until delivery significantly reduces the incidence of PROM to 13%, compared to 34% with placebo (109097).
• Radiation-induced diarrhea. It is unclear if oral selenium reduces diarrhea in patients receiving radiation therapy for cancer. Details: A small clinical study in patients with cervical or endometrial cancer shows that taking selenium 500 mcg on days of radiation therapy and 300 mcg on days without radiation therapy reduces the incidence of radiation-induced diarrhea to 20.5%, compared to 44.5% in the control group not taking selenium. This benefit appears to be more pronounced in patients receiving a larger (>1302 mL) planning target volume of radiation (90355).
• Rheumatoid arthritis (RA). It is unclear if oral selenium reduces RA symptoms. Details: A small clinical study in patients with RA suggests that taking selenized yeast, providing selenium 200 mcg, daily for 90 days does not improve objective measures of RA when compared with placebo. However, there might be small improvements in quality of life measures (9763). Another small clinical study in Iranian patients with moderate to severe RA shows that taking selenium 200 mcg twice daily for 12 weeks in addition to standard treatment reduces patient-reported disease activity, difficulty in performing activities of daily living, and pain severity but does not change the number of tender or swollen joints, erythrocyte sedimentation rate, or disease activity as measured by Disease Activity Score of 28 Joints (DAS28) when compared with placebo (113648).
• Schizophrenia. Oral selenium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with schizophrenia shows that taking a combination of selenium (Nature Made) 200 mcg and a combination probiotic mixture (LactoCare, Zisttakhmir Company) daily for 12 weeks modestly improves general positive and negative symptoms of schizophrenia, but not positive or negative scores, when compared with placebo. There were also modest improvements in levels of high-sensitivity C-reactive protein (CRP), fasting glucose, insulin resistance, and insulin sensitivity, but not lipid parameters (109087).
• Seborrheic dermatitis. It is unclear if topical selenium disulfide shampoo is beneficial for seborrheic dermatitis. Details: A very large observational study in adults with dandruff or seborrheic dermatitis suggests that applying selenium disulfide-based shampoo 2-3 times weekly for 4 weeks improves scalp condition and reduces flaking, erythema, and irritation when compared to baseline (113652). The validity of the results is limited by the observational nature of the study and lack of comparator group. A small clinical study in adults with moderate-to-severe seborrheic dermatitis shows that applying selenium disulfide-based 1% shampoo to the scalp once weekly for 8 weeks after a 2-week treatment with corticosteroid and salicylic acid combination therapy reduces relapse rate, erythema, pruritis, adherent dandruff, and total dandruff but does not improve non-adherent dandruff when compared with a placebo shampoo (113646).
• Statin-induced myopathy. Small clinical studies suggest that oral selenium may not improve symptoms of myopathy in patients taking statins. Details: Small clinical studies in patients with statin-induced myopathy suggests that taking selenium (SelenoPrecise, Pharma Nord) 200 mcg daily with or without coenzyme Q10 for 3 months does not improve myopathy symptoms when compared with placebo (92908,92909).
• Stroke. It is unclear if intravenous selenium improves neurological outcomes following a stroke. Details: A small clinical trial in patients with a recent first ischemic stroke shows that intravenous sodium selenite pentahydrate (Selenase, Biosyn, Arzenitmittel GmbH) 2000 mcg after admission and then 1000 mcg daily for 5 days modestly improves some, but not all, measures of neurological deficits when compared with placebo (109088). Another small clinical trial in patients with a recent ischemic stroke shows that the same intervention improves some neurological outcome measures on day 7 or at an earlier discharge, but benefits were not maintained at 3 months (109093). The effects of oral selenium on neurological outcomes following a stroke have not been investigated.
• Subarachnoid hemorrhage. Intravenous selenium has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized study in adults with aneurysmal subarachnoid hemorrhage shows that administering intravenous selenium 800 mcg and acetylcysteine 1000 mg twice daily starting within 24 hours of admission for 14 days reduces total days spent in the intensive care unit but does not change neurological outcomes, time to reach target sedation, duration of hospital stay, or need for tracheostomy when compared with intravenous placebo. Additionally, no change in radiological outcomes including hematoma or perihematomal edema volume, midline shifting, or the incidence of radiological vasospasm, angioplasty for vasospasm, or hydrocephalus was observed when compared with placebo (113644). It is unclear whether this effect is due to selenium, acetylcysteine, or the combination.
• Succinylcholine-induced myalgia. It is unclear if oral selenium is beneficial for preventing succinylcholine-induced postoperative myalgia. Details: Clinical research in patients receiving succinylcholine for a sinuscopy shows that taking a single dose of selenium 200 mcg 2 hours before anesthesia induction modestly decreases the incidence of postoperative myalgia at 24 hours. In those taking selenium, 95% of patients had no postoperative myalgia, compared with 77.5% of those taking placebo. Postoperative analgesia requirements were also modestly reduced; however, there was no difference in overall pain or the incidence of muscle twitching (109089).
• Thyroid cancer. It is unclear if oral selenium reduces the risk of thyroid cancer in most patients. Details: In 2009, the US Food and Drug Administration (FDA) approved a qualified health claim regarding selenium and thyroid cancer risk. This qualified health claim was based on one weak and limited study. The FDA has determined that it is highly uncertain that selenium supplements reduce the risk of thyroid cancer (102373). More recent observational research in postmenopausal individuals using data from the Women's Health Initiative has found that selenium intake at or above the recommended daily allowance from dietary sources or supplements is not associated with a decreased risk of thyroid cancer (110590).
• Ulcerative colitis. It is unclear if oral selenium is beneficial for ulcerative colitis. Details: A small clinical study in Iranian adults with mild-to-moderate ulcerative colitis shows that taking selenomethionine 200 mcg daily for 10 weeks in addition to standard therapy improves disease activity and quality of life and increases the percentage of patients with clinical improvement and clinical remission when compared with placebo (113643). Selenium has also been evaluated in combination with other ingredients. A clinical study in patients with ulcerative colitis shows that taking a liquid supplement containing a combination of selenium, fish oil, fructo-oligosaccharides, acacia, vitamin E, and vitamin C daily for 6 months does not improve disease activity scores when compared with placebo. However, taking the combination supplement seems to reduce the need for oral prednisone for symptom control (13757). More evidence is needed to rate selenium for these uses.

(Read more about SELENIUM)

There is insufficient reliable information available about the effectiveness of spleen extract.

(Read more about SPLEEN EXTRACT)

POSSIBLY EFFECTIVE

• Dilated cardiomyopathy. Small clinical trials show that adding subcutaneous thymomodulin to conventional treatment improves clinical and laboratory measures in patients with symptomatic dilated cardiomyopathy and reduced left ventricular ejection fraction (LVEF). Details: Clinical research in adults with symptomatic dilated cardiomyopathy and reduced LVEF shows that using subcutaneous thymomodulin (calf thymus extract) 10 mg three times weekly for 3 months in combination with conventional therapy improves LVEF after 2 years and also improves exercise tolerance, LVEF, clinical symptoms, and survival after a 7-year follow-up period when compared with conventional therapy alone. Thymomodulin was similarly effective to treatment with interferon-alpha (78542,78556,78558). The conventional treatments used in these studies, which were conducted in the early 1990s, involved an escalating regimen of salt reduction, digoxin, furosemide, captopril, metolazone, and warfarin.
• Respiratory tract infections. Low-quality clinical research in adults and children with recurrent respiratory tract infections suggest that oral thymus extract may modestly reduce infection frequency and symptom severity and duration. Details: Low-quality clinical studies show that taking thymus extract 120 mg orally daily, for 20 days of each month for up to 4 consecutive months during fall and winter, reduces the number of infections or coughing attacks in adults and children with recurrent respiratory infections when compared with placebo or no treatment (6697,6698,6699). One study also shows that oral thymomodulin modestly reduces the use of antibiotics and the duration of infection when compared with no treatment (938).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral thymus extract for hay fever, there is insufficient reliable information about the clinical effects of thymus extract for this purpose.
• Asthma. It is unclear if oral thymus extract is beneficial in children with asthma. Details: Preliminary clinical research in children 2-12 years of age with asthma shows that taking thymomodulin (calf thymus extract) 80 mg orally daily for 90 days reduces the frequency of acute asthma attacks when compared to baseline (6694). The validity of these findings is limited by the lack of a comparator group and the lack of information on the use of maintenance asthma therapy.
• Cancer. Although there has been interest in using oral thymus extract for cancer, there is insufficient reliable information about the clinical effects of thymus extract for this purpose.
• Chronic fatigue syndrome (CFS). Although there has been interest in using oral thymus extract for CFS, there is insufficient reliable information about the clinical effects of thymus extract for this purpose.
• Food allergies. Small clinical trials suggest that oral thymomodulin improves food tolerance in children with food allergies. Details: Two small clinical studies in children 7 months to 14 years of age with food allergies shows that taking thymomodulin (calf thymus extract) 120 mg daily for three months while on an elimination diet improves tolerance to allergenic foods when compared to an elimination diet alone (1175,1176).
• Hepatitis. Although there has been interest in using oral thymus extract for hepatitis, there is insufficient reliable information about the clinical effects of thymus extract for this purpose.
• Herpes labialis (cold sores). Although there has been interest in using oral thymus extract for cold sores, there is insufficient reliable information about the clinical effects of thymus extract for this purpose.
• Herpes zoster (shingles). Although there has been interest in using oral thymus extract for shingles, there is insufficient reliable information about the clinical effects of thymus extract for this purpose.
• Rheumatoid arthritis (RA). Although there has been interest in using oral thymus extract for RA, there is insufficient reliable information about the clinical effects of thymus extract for this purpose.
• Systemic lupus erythematosus (SLE). Although there has been interest in using oral thymus extract for SLE, there is insufficient reliable information about the clinical effects of thymus extract for this purpose. More evidence is needed to rate thymus extract for these uses.

(Read more about THYMUS EXTRACT)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Hypothyroidism. Although there has been interest in using oral thyroid extract for hypothyroidism, there is insufficient reliable information about the clinical effects of thyroid extract for this purpose.
• Infertility. It is unclear if oral thyroid extract is beneficial in females with infertility. Details: A small clinical study in female patients with infertility caused by luteal-phase deficiency shows that taking a specific thyroid extract (Thyranon) 25 mg daily to start, and then doubling the dose every 2 weeks to a maximum 100 mg daily, for three menstrual cycles increases pregnancy rate when compared with placebo. Of the patients receiving thyroid extract, 8 out of 17 became pregnant by the fourth month, while only 1 out of 7 patients in the placebo group became pregnant (28618).
• Thyroid cancer. Although there has been interest in using oral thyroid extract after treatment for thyroid cancer, there is insufficient reliable information about the clinical effects of thyroid extract for this purpose. More evidence is needed to rate thyroid extract for these uses.

(Read more about THYROID EXTRACT)

EFFECTIVE

• Phenylketonuria (PKU). Oral tyrosine as a component of medical foods is recommended in people with PKU, a disorder in which phenylalanine cannot be endogenously metabolized into tyrosine. Details: Tyrosine is used as a component of medical foods for people with phenylketonuria (PKU) (7212,7213,7232). Current guidelines recommend that people with PKU maintain a diet low in phenylalanine and incorporate tyrosine as a component of medical foods to maintain normal blood levels of tyrosine (95108). Supplementation with additional tyrosine is recommended only for patients with consistently low blood levels of tyrosine despite using tyrosine-containing medical foods (95108). Routine supplementation with free tyrosine is not recommended for most patients because it can produce wide variations in tyrosine plasma concentrations and side effects (7212,95108). Tyrosine intake does not improve neuropsychological measures in patients with PKU (81503,91471,95108).

POSSIBLY EFFECTIVE

• Cognitive function. Oral tyrosine might improve cognitive function, particularly in patients exposed to stressors such as excessive cold, noise, or sleep deprivation. Details: Most research suggests that taking tyrosine orally improves cognitive function, particularly under stressful conditions. Small clinical studies in healthy adults show that taking tyrosine 100-300 mg/kg in the setting of exposure to stressors such as excessive cold, noise, or sleep deprivation improves cognitive performance measures, such as executive function and short-term memory, when compared with placebo (7215,81472,81476,81484,81501). Other small clinical studies in healthy patients show that taking tyrosine 2 grams may improve response time without detracting from performance and could improve some measures of cognitive response to conflict when compared with placebo (101082,111248). Some of these small studies may be inadequately powered to detect an effect on some cognitive function tests. Tyrosine has also been evaluated in combination with other ingredients for this purpose. A small clinical study in healthy adults with fatigue shows that taking tyrosine, serine, alanine, glutamate, and aspartate daily for 4 weeks improves measures of cognitive function including attention, spatial cognition, orientation, motivation, and time management when compared with placebo (111249). It is unclear if these effects are due to tyrosine, other ingredients, or the combination.
• Memory. Taking tyrosine orally seems to improve memory in patients exposed to stressors such as cold or those having to complete multiple tasks at once. Details: Small clinical studies in healthy adults show that taking tyrosine 150-300 mg/kg prior to acute exposure to stress that is cold-induced, noise-induced, or induced by multi-tasking improves memory performance when compared with placebo (81469,81477,81499,81501). However, tyrosine 150 mg/kg does not seem to improve memory in less stressful situations such as performing one simple task or testing when not exposed to cold (81469,81499).

POSSIBLY INEFFECTIVE

• Athletic performance. Oral tyrosine does not improve athletic performance when taken prior to exercise. Details: Clinical studies show that taking tyrosine orally prior to participating in treadmill or cycling exercises conducted at temperate temperatures or in the heat does not improve strength, endurance, or performance when compared with placebo (81471,81474,81504,91470,104403). Another very small clinical study in healthy males shows that taking a multi-ingredient pre-workout supplement containing L-tyrosine, beta-alanine, L-citrulline maleate, arginine alpha-ketoglutarate, L-taurine, and caffeine does not increase bench press strength endurance when compared with equivalent amounts of anhydrous caffeine (111250).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alcohol use disorder. Oral tyrosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with alcohol use disorder shows that taking a combination of tyrosine 900 mg, D,L-phenylalanine 1.5 grams, L-glutamine 300 mg, and L-tryptophan 400 mg daily along with a multivitamin supplement reduces withdrawal symptoms and decreases stress when compared with placebo (81552). It is unclear if these effects are due to tyrosine, other ingredients, or the combination.
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral tyrosine is beneficial for improving ADHD symptoms. Details: A very small clinical study shows that taking tyrosine does not improve symptoms of ADHD in children when compared with baseline (7209). Furthermore, another very small clinical trial in adults with ADHD shows that taking tyrosine daily for 8 weeks does not improve inattention when compared with baseline. Some patients might have transient symptom improvement after 2 weeks, but seem to acquire tolerance by 6 weeks (7210). The validity of these findings is limited by the small study size and lack of control groups.
• Cocaine dependence. Oral tyrosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with cocaine dependence shows that taking L-tyrosine 1 gram in the morning and L-tryptophan 1 gram in the evening for 14 days does not reduce drug cravings or withdrawal symptoms when compared with placebo (81480).
• Dementia. Oral tyrosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in patients with severe Alzheimer disease or multi-infarct dementia shows that taking a combination of tyrosine 4 grams, 5-HTP 800 mg, and carbidopa 100 mg orally daily does not improve clinical or psychological parameters in most patients when compared with baseline (918). The validity of this finding is limited by the small study size and a lack of control group.
• Depression. It is unclear if oral tyrosine is beneficial for improving major depressive disorder. Details: A small clinical study in patients with major depression shows that taking L-tyrosine 100 mg/kg daily for 4 weeks does not improve depressive symptoms when compared with placebo (7208).
• Erectile dysfunction (ED). Although there is interest in using oral tyrosine for ED, there is insufficient reliable information about the clinical effects of tyrosine for this condition.
• Fatigue. Oral tyrosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy adults with fatigue shows that taking tyrosine, serine, alanine, glutamate, and aspartate daily for 4 weeks does not improve subjective or objective measures of fatigue when compared with placebo (111249).
• Hypertension. It is unclear if oral tyrosine is beneficial for reducing hypertension of mild severity. Details: A very small clinical study in patients with mild essential hypertension shows that taking oral tyrosine 2.5 grams three times daily with meals for 2 weeks does not affect systolic or diastolic blood pressure when compared with control (81487).
• Mitochondrial myopathies. Although there is interest in using oral tyrosine for nemaline myopathy, a type of mitochondrial myopathy, there is insufficient reliable information about the clinical effects of tyrosine for this condition.
• Narcolepsy. It is unclear if oral tyrosine is beneficial for improving narcolepsy symptoms. Details: A small clinical study in patients with narcolepsy shows that taking capsules containing tyrosine 3 grams orally three times daily for 4 weeks might reduce feelings of tiredness or drowsiness when compared with placebo, but the overall effect is not clinically significant. Tyrosine also does not seem to improve sudden muscle weakness, sleep paralysis, night-time sleep, sleep latency, or speed and attention after waking when compared with placebo (81482).
• Obesity. Oral tyrosine has only been evaluated for in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in overweight or obese patients shows that taking a supplement containing tyrosine 1.2 grams, cayenne 450 mg, green tea 1.5 grams, caffeine 150 mg, and calcium carbonate 3.89 grams daily for 8 weeks slightly reduces body fat mass by 0.9 kg when compared with placebo (81475). It is not clear if any potential benefit is due to tyrosine, other ingredients, or the combination.
• Opioid withdrawal. Oral tyrosine has only been evaluated for heroin withdrawal in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in Chinese males undergoing detoxification for heroin addiction shows that taking a combination of tyrosine 50 mg/kg, 5-HTP 200 mg, phosphatidylcholine 1200 mg, and L-glutamine 50 mg/kg daily for 6 days can reduce insomnia and withdrawal symptoms and improve mood when compared with placebo (88178). It is not clear if this effect is due to tyrosine, other ingredients, or the combination.
• Parkinson disease. Although there is interest in using oral tyrosine for Parkinson disease, there is insufficient reliable information about the clinical effects of tyrosine for this condition.
• Premenstrual syndrome (PMS). Although there is interest in using oral tyrosine for PMS, there is insufficient reliable information about the clinical effects of tyrosine for this condition.
• Schizophrenia. It is unclear if oral tyrosine is beneficial for improving schizophrenia symptoms. Details: A very small clinical study in patients with schizophrenia shows that taking L-tyrosine 10 grams daily in four divided doses along with molindone 150 mg daily for 3 weeks does not improve symptoms of schizophrenia when compared with taking molindone alone (81554).
• Sleep deprivation. It is unclear if oral tyrosine is beneficial for improving alertness in sleep deprived adults. Details: A small clinical study shows that taking tyrosine 150 mg/kg after the loss of a night's sleep seems to delay performance decline in psychomotor tests by about 3 hours when compared with placebo (7215). Another small clinical study in sleep-deprived patients shows that taking tyrosine 150 mg/kg improves memory, reasoning, and vigilance when compared with placebo at 5.5 hours after ingestion, but not at 1.5 hours. Tyrosine was less effective than taking amphetamine, phentermine, or caffeine (81472).
• Stress. Although there is interest in using oral tyrosine for stress, there is insufficient reliable information about the clinical effects of tyrosine for this condition.
• Wrinkled skin. Topical tyrosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small study in patients with photodamaged skin shows that applying a topical preparation containing 10% vitamin C, acetyl tyrosine, zinc sulfate, sodium hyaluronate, and bioflavonoids (High Potency Serum, Cellex-C International Inc.) for 3 months to the face seems to improve fine and coarse wrinkling, yellowing and sallowness, roughness, and skin tone when compared with placebo (6155). It is unclear if the benefits are due to tyrosine, other ingredients, or the combination. More evidence is needed to rate the effectiveness of tyrosine for these uses.

(Read more about TYROSINE)

LIKELY UNSAFE ...when used parenterally. Use of injectable adrenal extract has been associated with at least 50 cases of serious bacterial infections at injection sites (6620). Adrenal extracts are derived from animals so there is concern about contamination with diseased animal parts. So far, there are no reports of disease transmission to humans due to use of contaminated adrenal extracts. There is insufficient reliable information available about the safety of adrenal extract for its other uses.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about ADRENAL EXTRACT)

LIKELY SAFE ...when undegraded carrageenan is used orally in the amounts found in foods (11). Carrageenan has Generally Recognized as Safe (GRAS) status in the US (4912,102538).

POSSIBLY SAFE ...when used intranasally, short-term. Saline solution containing iota-carrageenan 0.12% has been sprayed into the nose with apparent safety three times daily for up to 7 days (99449,99450,99451,99452,99466). Also, saline solution containing iota-carrageenan 0.17% has been sprayed into both nostrils with apparent safety four times daily (providing 1 mg daily) for up to 21 days (107852).

POSSIBLY UNSAFE ...when the degraded form, called poligeenan, is used orally. Poligeenan contains a lower molecular weight product that is partially absorbed. There is concern about the safety of this form because it has been linked to colonic lesions, neoplasms, and bleeding in animals (40065,40047). Due to public concern that commercial carrageenan contains poligeenan or can be degraded to poligeenan in the stomach, the United States Food and Drug Administration (FDA) reevaluated the safety of carrageenan and reaffirmed its status as GRAS in 2012 (99466). Carrageenan that is not degraded has an average molecular weight of 453-652 kDA, while degraded carrageenan is usually 20-30 kDA. In order to limit potential safety concerns, the European Commission Scientific Committee on Food advises that the total weight of any carrageenan food additives contain no more than 5% of a molecular weight below 50 kDa (99901). There is insufficient reliable information available about the safety of carrageenan when used topically.

PREGNANCY AND LACTATION: LIKELY SAFE
when used in food amounts (11). There is insufficient reliable information available about the safety of using larger amounts; avoid using.

(Read more about CARRAGEENAN)

LIKELY SAFE ...when used orally in food amounts. Dulse has a long history of use as a food ingredient in various parts of the world (103315,103317,103321).

POSSIBLY SAFE ...when used topically and appropriately (103322). There is insufficient reliable information available about the safety of dulse when used in amounts greater than those found in foods.

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of dulse when used in medicinal amounts during pregnancy or lactation; avoid amounts greater than those found in foods.

(Read more about DULSE)

POSSIBLY SAFE ...when applied topically to the skin. A gel containing 1% Fucus vesiculosus extract, applied to the skin twice daily, has been used in clinical research with apparent safety for up to 5 weeks (12799).

POSSIBLY UNSAFE ...when used orally due to its iodine content and possible heavy metal content. Fucus vesiculosus contains up to 0.05% iodine or 226 mcg/gram dry weight (12789,74217). Ingesting more than 150 mcg of iodine daily can cause hyperthyroidism or exacerbate existing hyperthyroidism (12788). Fucus vesiculosus can also contain heavy metals, including cadmium, arsenic, and lead, and can cause heavy metal nephropathy (12789,12800,74213).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally because it may contain iodine and heavy metals (12789,74213,74217); avoid using.

(Read more about FUCUS VESICULOSUS)

LIKELY SAFE ...when used orally and appropriately. Iodine is safe in amounts that do not exceed the tolerable upper intake level (UL) of 1100 mcg daily (7135,103070). Higher doses can be safely used with appropriate medical monitoring (2197,7080). In some regions of the world, such as Japan, daily dietary intake is estimated to be as high as 5,280-13,800 mcg without adverse outcomes (16747). ...when used topically and appropriately, as a 2% solution. A 2% iodine solution is an FDA-approved prescription product (15).

POSSIBLY UNSAFE ...when used orally in high doses. Tell patients to avoid prolonged use of doses exceeding the UL of 1100 mcg daily without proper medical supervision. There is concern that higher intake can increase the risk of side effects such as thyroid dysfunction, as well as thyroiditis, thyroid papillary cancer, thyrotoxicosis, and atrial fibrillation (7135,55962,56013). However, in some regions of the world such as Japan, daily dietary intake is estimated to be as high as 5,280-13,800 mcg without adverse outcomes (16747).

CHILDREN: LIKELY SAFE
when used orally and appropriately (7135). Iodine is safe in amounts that do not exceed the tolerable upper intake level (UL) of 200 mcg daily for children 1-3 years, 300 mcg daily for children 4-8 years, 600 mcg daily for children 9-13 years, and 900 mcg daily for adolescents (7135). ...when used topically as a 2% solution (15). Iodine is an FDA-approved prescription product.

CHILDREN: POSSIBLY UNSAFE
when used orally in doses exceeding the UL (7135,108709). Higher intake can cause thyroid dysfunction (7135) and may be associated with a modest reduction in intelligence (108709).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately. Iodine is safe in amounts that do not exceed the tolerable upper intake level (UL) of 1100 mcg daily in those 18 years and older or 900 mcg daily in those 14-18 years of age (7135,103070). Iodine needs increase during pregnancy and lactation and adequate intakes should begin as soon as a patient is aware of the pregnancy, or earlier in areas of potential deficiency (17920). ...when used topically as a 2% solution (15). Iodine is an FDA-approved prescription product.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in doses exceeding the UL. Higher intake can cause thyroid dysfunction (7135). Also, higher intakes during pregnancy cause increased iodine levels in breast milk and infant blood samples. Higher iodine intake during pregnancy has also been associated with an increased risk of congenital hypothyroidism and reduced mental and physical development in the offspring (56089,91390,91394,91395).

(Read more about IODINE)

LIKELY SAFE ...when used orally and appropriately. Selenium appears to be safe when taken short-term in amounts below the tolerable upper intake level (UL) of 400 mcg daily (4844,7830,7831,7836,7841,9724,9797,14447,17510,17511)(17512,17513,17515,17516,97087,97943,109085); however, there is concern that taking selenium long-term might not be safe. Some evidence shows that consuming a diet containing more than the recommended dietary allowance (RDA) of selenium, which is 55 mcg daily for most adults, is associated with an increased risk for developing type 2 diabetes (99661). Some evidence also shows that taking a selenium supplement 200 mcg daily for an average of 3-8 years increases the risk of developing type 2 diabetes (97091,99661). Higher serum levels of selenium are also associated with an increased risk of developing diabetes and increased mortality (16710,99661). ...when used intravenously. Selenium, as selenious acid, is an FDA-approved drug. Sodium selenite intravenous infusions up to 1000 mcg daily have been safely used for up to 28 days (90347,92910).

POSSIBLY UNSAFE ...when used orally in high doses or long-term. Doses above 400 mcg daily can increase the risk of developing selenium toxicity (4844,7825). Additionally, some evidence shows that consuming a diet containing more than the recommended dietary allowance (RDA) of selenium, which is 55 mcg daily for most adults, is associated with an increased risk for developing type 2 diabetes (99661). There is also concern that taking a selenium supplement 200 mcg daily long-term, for an average of 3-8 years, increases the risk of developing type 2 diabetes (99661). Higher serum levels of selenium are also associated with an increased risk of developing diabetes and increased mortality (16710,99661).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. Selenium seems to be safe when used short-term in doses below the tolerable upper intake level (UL) of 45 mcg daily for infants up to age 6 months, 60 mcg daily for infants 7 to 12 months, 40-90 mcg daily for children 1 to 3 years, 100-150 mcg daily for children 4 to 8 years, 200-280 mcg daily for children 9 to 13 years, and 400 mcg daily for children age 14 years and older (4844,86095); however, there is some concern that long-term use might not be safe. ...when used via a nasogastric tube in premature infants (7835,9764).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately. Selenium appears to be safe when used short-term in amounts that do not exceed the tolerable upper intake level (UL) of 400 mcg daily (4844,17507,74419,74481,74391); however, there is concern that long-term use might not be safe.

PREGNANCY: POSSIBLY UNSAFE
when used orally in excessive doses. Doses above 400 mcg daily may cause significant toxicity (4844).

LACTATION: POSSIBLY SAFE
when used orally and appropriately. Selenium appears to be safe when used short-term in amounts that do not exceed the tolerable upper intake level (UL) of 400 mcg daily when taken short-term (4844,74467); however, there is concern that long-term use might not be safe.

LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses. Doses above 400 mcg daily may cause significant toxicity (4844,7838). ...when used orally in HIV-positive women. Selenium supplementation in HIV-positive women not taking highly active antiretroviral therapy may increase HIV-1 levels in breast milk (90358).

(Read more about SELENIUM)

There is insufficient reliable information available about the safety of spleen extract. There is some concern about contamination with diseased animal parts since spleen extract preparations are derived from animals (1825). However, there are no reports of disease transmission to humans due to use of contaminated spleen extract.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about SPLEEN EXTRACT)

POSSIBLY SAFE ...when used orally and appropriately. Purified thymus extract has been used with apparent safety in clinical trials (938,1175,1176,1177,1178,6691,6694,6696,6697,6698,6699). Since thymus extract is derived from raw bovine thymus gland, there is some concern for contamination with diseases (1825). However, so far there are no reports of disease transmission to humans due to use of contaminated thymus extract. There is insufficient reliable information available about the safety of thymus extract when used subcutaneously or intramuscularly.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about THYMUS EXTRACT)

POSSIBLY UNSAFE ...when taken orally. Thyroid extract contains triiodothyronine (T3) and thyroxine (T4) (29981). However, the potency of these hormones varies, making dose titration difficult (29982,29983,29984,109614). Using thyroid extract increases the risk of hyperthyroidism and associated cardiac and neurological complications (28621,29987,97621).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

(Read more about THYROID EXTRACT)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Tyrosine has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Tyrosine has been used safely in doses up to 150 mg/kg daily for up to 3 months (7210,7211,7215). ...when used topically and appropriately (6155).

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of tyrosine during pregnancy and lactation when used in medicinal amounts. Some pharmacokinetic research shows that taking a single dose of tyrosine 2-10 grams orally can modestly increase levels of free tyrosine in breast milk. However, total levels are not affected, and levels remain within the range found in infant formulas. Therefore, it is not clear if the increase in free tyrosine is a concern (91467).

(Read more about TYROSINE)

(Read more about ADRENAL EXTRACT)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, carrageenan may increase the risk of bleeding in patients taking anticoagulant or antiplatelet drugs.  Details Laboratory research suggests that carrageenan has anticoagulant effects (6002). However, this has not been reported in humans.

(Read more about CARRAGEENAN)

ACE INHIBITORS (ACEIs) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, dulse might increase the risk of hyperkalemia when taken with ACEIs.  Details Dulse is rich in potassium (103317). ACEIs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion (95628). Concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels (95628). However, using these drugs while consuming dulse in quantities that provide larger amounts of potassium daily might increase the risk of hyperkalemia. Additionally, in vitro research suggests that dulse protein hydrolysates inhibit the activity of ACE (103319). However, these effects have not been demonstrated in humans.

AMIODARINE (Cordarone) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining dulse with amiodarone might cause excessively high iodine levels.  Details Dulse is rich in iodine (103315,103323), and amiodarone contains 37.3% iodine and can increase iodine levels.

ANGIOTENSIN RECEPTOR BLOCKERS (ARBs) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, dulse might increase the risk of hyperkalemia when taken with ARBs.  Details Dulse is rich in potassium (103317). ARBs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion (95628). Concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels (95628). However, using these drugs while consuming dulse in quantities that provide higher amounts of potassium daily might increase the risk of hyperkalemia. Additionally, in vitro research suggests that dulse protein hydrolysates inhibit the activity of angiotensin converting enzyme (ACE) (103319). However, these effects have not been demonstrated in humans.

ANTITHYROID DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, due to its iodine content, dulse might alter the effects of antithyroid drugs.  Details Dulse is rich in iodine (103315,103323). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history.

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, dulse might increase the risk of hyperkalemia when taken with digoxin.  Details Dulse is rich in potassium, and digoxin can increase potassium levels in the blood (103317). This interaction has not been demonstrated in humans.

POTASSIUM-SPARING DIURETICS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, dulse might increase the risk of hyperkalemia when taken with potassium-sparing diuretics.  Details Dulse is rich in potassium, and potassium-sparing diuretics can increase potassium levels in the blood (103317). This interaction has not been shown in humans.

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, due to its iodine content, dulse might alter the effects of thyroid hormone.  Details Dulse is rich in iodine (103315,103323). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Although dulse has been associated with a statistically significant increase in thyroid stimulating hormone (TSH) levels in clinical research, clinically significant increases have not been documented (103315,103323).

(Read more about DULSE)

AMIODARONE (Cordarone) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, combining Fucus vesiculosus with amiodarone might cause excessively high iodine levels.  Details Fucus vesiculosus contains high concentrations of iodine (7135). Amiodarone contains 37.3% iodine and can increase iodine levels. Concomitant use might increase the risk of having excessive iodine levels and adversely affecting thyroid function (7135,17574). Monitor thyroid function.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, taking Fucus vesiculosus with antiplatelet or anticoagulant drugs might increase the risk of bruising and bleeding.  Details In vitro evidence suggests that a constituent of Fucus vesiculosus, known as fucoidan, has anticoagulant effects (12797,74149,74183,74240). However, in clinical research, fucoidan does not seem to have significant anticoagulant activity when taken orally, possibly due to poor absorption (74183).

ANTITHYROID DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Due to its iodine content, Fucus vesiculosus might alter the effects of antithyroid drugs.  Details Fucus vesiculosus contains high concentrations of iodine (7135). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking Fucus vesiculosus while using antithyroid drugs could alter the effects of the antithyroid drugs (2138,17574).

CYTOCHROME P450 2C8 (CYP2C8) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Fucus vesiculosus with CYP2C8 substrates might increase the risk for adverse effects.  Details In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, inhibits CYP2C8 (97791). This interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Fucus vesiculosus with CYP2C9 substrates might increase the risk for adverse effects.  Details In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, inhibits CYP2C9 (97791). This interaction has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Fucus vesiculosus with CYP2D6 substrates might alter the effects of these substrates.  Details In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, both inhibits and induces CYP2D6 (97791). This interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of Fucus vesiculosus with CYP3A4 substrates might increase the risk for adverse effects.  Details In vitro research shows that fucoidan, a constituent of Fucus vesiculosus, inhibits CYP3A4 (97791). This interaction has not been reported in humans.

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant use of Fucus vesiculosus and lithium has resulted in hyperthyroidism.  Details There is a case of hyperthyroidism occurring in a patient taking Fucus vesiculosus and lithium (74217). Monitor thyroid hormones closely in patients taking lithium and Fucus vesiculosus concomitantly.

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Due to its iodine content, Fucus vesiculosus might alter the effects of thyroid hormone.  Details Fucus vesiculosus contains high concentrations of iodine (7135). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking Fucus vesiculosus while using thyroid hormone could alter the effects of thyroid hormone.

(Read more about FUCUS VESICULOSUS)

AMIODARONE (Cordarone) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Combining iodine with amiodarone might cause excessively high iodine levels.  Details Amiodarone contains 37.3% iodine and can increase iodine levels. Concomitant use with iodine might increase the risk of having excessive iodine levels and adversely affecting thyroid function (7135,17574). Monitor thyroid function.

ANTITHYROID DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Iodine might alter the effects of antithyroid drugs.  Details Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking iodine while using antithyroid drugs could alter the effects of the antithyroid drugs (2138,17574).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Combining iodine with lithium might have additive hypothyroid effects.  Details Lithium can inhibit thyroid function. Several case reports suggest that concomitant use of lithium and potassium iodide can reduce thyroid function in otherwise healthy adults (17574). Monitor thyroid function.

(Read more about IODINE)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Selenium may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Clinical research suggests that taking selenium 10 mcg/kg/day can increase bleeding times by increasing prostacyclin production, which inhibits platelet activity (14540). Other clinical research suggests that taking selenium 75 mcg daily, in combination with ascorbic acid 600 mg, alpha-tocopherol 300 mg, and beta-carotene 27 mg, reduces platelet aggregation (74406).

BARBITURATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, selenium might prolong the sedating effects of barbiturates.  Details Laboratory research suggests that selenium can inhibit the hepatic metabolism of barbiturates (14601,14602). Selenium seems to prolong the sedative effect of pentobarbital in animal models (14601).

CONTRACEPTIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = B Contraceptive drugs might increase levels of selenium, although the clinical significance of this effect is unclear.  Details Some research suggests that oral contraceptives increase serum selenium levels in women taking oral contraceptives; however, other research shows no change in selenium levels (14544,14545,14546,101343). It is suggested that an increase could be due to increased carrier proteins, indicating a redistribution of selenium rather than a change in total body selenium (14545).

GOLD SALTS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Gold salts might interfere with selenium activity in tissues.  Details Gold forms complexes with selenium, altering its tissue distribution. Theoretically, this might prevent the normal activity of selenium and produce effects equivalent to deficiency (14547,14548).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, selenium supplementation may reduce the effectiveness of immunosuppressant therapy.  Details In vitro research and preliminary clinical evidence suggests that selenium may stimulate the immune system (74483,74445).

NIACIN Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = A Selenium might reduce the beneficial effects of niacin on high-density lipoprotein (HDL) levels.  Details A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease (7388,11537). It is not known whether this adverse effect is due to a single antioxidant such as selenium, or to the combination. It also is not known whether it will occur in other patient populations.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, selenium might interfere with warfarin activity.  Details Animal research suggests that selenium can increase warfarin activity. Selenium might interact with warfarin by displacing it from albumin binding sites, reducing its metabolism in the liver, or by decreasing production of vitamin K-dependent clotting factors (14541). Selenium can also prolong bleeding times in humans by increasing prostacyclin production, which inhibits platelet activity (14540).

(Read more about SELENIUM)

(Read more about SPLEEN EXTRACT)

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, patients taking immunosuppressants may be at an increased risk of infection from contaminated thymus extract.  Details Thymus extract is derived from raw bovine thymus glands and is at risk for contamination (1825). Tell patients to avoid thymus extract products unless these products are certified as pathogen-free.

(Read more about THYMUS EXTRACT)

LEVOTHYROXINE (Synthroid, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, thyroid extract might increase the effects and adverse effects of levothyroxine.  Details Thyroid extract contains triiodothyronine (T3) and thyroxine (T4) (29981,97621). Taking thyroid extract increases blood levels of T3 and T4, in some cases to abnormally high levels (28621,29987,97621).

(Read more about THYROID EXTRACT)

LEVODOPA Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, tyrosine might decrease the effectiveness of levodopa.  Details Tyrosine and levodopa compete for absorption in the proximal duodenum by the large neutral amino acid (LNAA) transport system (2719). Advise patients to separate doses of tyrosine and levodopa by at least 2 hours.

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, tyrosine might have additive effects with thyroid hormone medications.  Details Tyrosine is a precursor to thyroxine and might increase levels of thyroid hormones (7212).

(Read more about TYROSINE)

General ...Orally and intravenously, adverse effects to adrenal extract seem to be rare; however, a thorough safety evaluation has not been conducted.
Most Common Adverse Effects:
Intravenously: Injection site reactions.
Serious Adverse Effects (Rare):
Intravenously: Serious bacterial infections at injection sites.

Dermatologic ...Intravenously, adrenal extract can cause infection and abscess at the site of injection (6620). In 1996, the FDA issued a nationwide alert regarding an injectable adrenal cortex extract after more than 50 cases of serious bacterial infections at injection sites were reported (6620).

Other ...Adrenal extracts are derived from raw cow, pig, or sheep adrenal glands gathered from slaughterhouses and possibly from sick or diseased animals (6620). Products made from contaminated or diseased organs might present a human health hazard. There is also some concern that adrenal extracts produced from cows in countries where bovine spongiform encephalitis (BSE) has been reported might be contaminated with diseased tissue. Countries where BSE has been reported include Great Britain, France, The Netherlands, Portugal, Luxembourg, Ireland, Switzerland, Oman, Belgium, and others (1825); however, there have been no reports of BSE transfer to humans from contaminated adrenal extract products. Until more is known, tell patients to avoid these products unless country of origin can be determined. Patients should avoid products that are produced in countries where BSE has been found.

(Read more about ADRENAL EXTRACT)

General ...Orally, carrageenan is well tolerated in amounts found in foods. Intranasally, carrageenan seems to be well tolerated.
Most Common Adverse Effects: None known.

Dermatologic ...Topically, when carrageenan gel was applied to the penis or anus prior to anal intercourse in one clinical study, it was reported to cause discomfort or adverse reactions in 59% of males, compared with 44% of those using placebo (107851).

Genitourinary ...Intravaginally, carrageenan gel has been associated with mild vaginal itching and burning, a vaginal abrasion, bladder fullness, and urinary hesitancy. However, it is unclear if carrageenan was the causal factor of these symptoms (40044,40068).

Hematologic ...In one clinical study in males, carrageenan gel applied topically to the penis and anus prior to anal intercourse was reported to cause rectal bleeding that was not directly related to anal intercourse in 8% of patients, compared with 0% of patients using placebo (107851).

Oncologic ...Observational research has found that increased consumption of carrageenan is associated with an increase in breast cancer incidence (40046).

(Read more about CARRAGEENAN)

General ...Orally, dulse is generally well tolerated. No adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.

(Read more about DULSE)

General ...When used orally, Fucus vesiculosus may be unsafe due to its iodine content. Topically, Fucus vesiculosus appears to be well tolerated.
Most Common Adverse Effects:
Orally: Goiter, hyperthyroidism, hypothyroidism.
Serious Adverse Effects (Rare):
Orally: Thyroid cancer.

Cardiovascular ...In one report, a young adult with obesity developed palpitations and syncope after taking an oral weight loss supplement containing a combination of Fucus vesiculosus, dandelion, and boldo for 3 weeks. The patient was found to have a prolonged QT interval on ECG and frequent episodes of sustained polymorphic ventricular tachycardia (14321). It is not clear whether Fucus vesiculosus, another ingredient, or the combination of ingredients is responsible for this adverse effect. The product was not analyzed to determine the presence of any potential toxic contaminants.

Endocrine ...Orally, Fucus vesiculosus can cause or exacerbate hyperthyroidism due to its high iodine content (12789,13061,74217). One case of hyperthyroidism has been reported for a 60-year-old patient taking lithium for bipolar disorder and a combination product containing Fucus vesiculosus 0.125 grams, cascara 0.170 grams, and Frangula 0.222 grams per tablet for laxative purposes. The patient had been taking one tablet of the combination laxative product daily for several years. Following discontinuation of the supplement, thyroid levels normalized (74217). Similar cases of hyperthyroidism have been reported for patients taking other seaweed-containing herbal supplements (Dream Shape; Ever Youth). Analyses of these supplements shows that these products contain triiodothyronine 1 mcg and thyroxine 3-4 mcg. In addition to seaweed, Dream Shape also contains hydrangea vine, maltose, chrysanthemum, Chinese matrimony vine, and sucrose, while Ever Youth contains radish, lotus leaf, chrysanthemum, hawthorn, senna tea, and Chinese matrimony vine (13061).
Orally, prolonged use of Fucus vesiculosus has been associated with hypothyroidism (13664). The iodine in Fucus vesiculosus can cause idiosyncratic reactions.
According to the Institute of Medicine Food and Nutrition Board, prolonged, high dietary intake of iodine is associated with goiter and an increased risk of thyroid cancer (7135).

Genitourinary ...A case of hemorrhagic cystitis characterized by dysuria and polyuria has been reported in a young adult who took a specific product (Slim-Kombu, Balestra and Mech) containing Fucus vesiculosus and 19 other herbal extracts orally for weight loss. Upon discontinuation, symptoms improved (46959). It is unclear if this effect was due to Fucus vesiculosus or other ingredients in the supplement.

Renal ...A case of hemorrhagic cystitis characterized by dysuria and polyuria has been reported in a young adult who took a specific product (Slim-Kombu, Balestra and Mech) containing Fucus vesiculosus and 19 other herbal extracts orally for weight loss. Upon discontinuation, symptoms improved (46959). It is unclear if this effect was due to Fucus vesiculosus or other ingredients in the supplement. Nephrotoxicity has been associated with oral intake of Fucus vesiculosus that was contaminated with arsenic (12800).

(Read more about FUCUS VESICULOSUS)

General ...Orally, iodine is well tolerated when taken in amounts that do not exceed the tolerable upper intake level (UL) or when used therapeutically with appropriate medical monitoring (2197,7080,7135).
Most Common Adverse Effects:
Orally: Abdominal upset, diarrhea, goiter, headache, hyperthyroidism, hypothyroidism, metallic taste, nausea, rhinorrhea, thyroid adenoma.
Topically: Burns, dermatitis, irritation.
Serious Adverse Effects (Rare):
All ROAs: Hypersensitivity reactions such as anaphylaxis and angioedema.

Dermatologic ...Orally, taking iodine chronically or in large amounts has been reported to cause acneform skin lesions called iododerma (2138). In one case, a patient developed iododerma after consuming a specific product (Hoxsey's Brown Tonic) containing an unspecified quantity of potassium iodide. After several months of consumption, the patient developed acneform skin lesions on the nose, cheeks, and upper back and presented with a urine iodine level of 7,455,647 ug/L (reference range: 34-523 ug/L). After discontinuation of potassium iodide, the lesions resolved gradually over the course of several weeks (95431).
Topically, iodine may stain skin, irritate tissues, and cause sensitization in some individuals (15,56106). Iodine burns are associated with application of 7% hydroalcoholic solution (15). Povidone-iodine may cause contact dermatitis or irritant reactions in some people. However, patch testing with potassium iodide is usually negative in these patients, indicating that contact dermatitis caused by topical iodine does not indicate a propensity for reaction to oral potassium iodide (93001).

Endocrine ...Prolonged use and/or large oral doses of iodine intake can cause thyroid gland hyperplasia, thyroid adenoma, goiter, and hypothyroidism (15,56013,56089,91397,91398,99793,99795). In another case report, an infant presented with reversible hypothyroidism at birth because the mother had consumed excessive seaweed soup during and after pregnancy, which resulted in excessive iodine consumption (99795). Iodine has also been linked to rare cases of adverse events. In one case report, a 56-year-old male developed thyrotoxic hypokalemic paralysis thought to be related to excessive intake of iodine (91401).
Topically, using povidone-iodine (PI) 1% solution as a gargle and nasal spray, in addition to intranasal application of PI 10% ointment over 5 days, can precipitate subclinical hypothyroidism, with elevated thyroid stimulating hormone (TSH) and normal thyroid hormone levels. TSH levels seem to normalize about 7-12 days after stopping topical PI application (105877).

Gastrointestinal ...Orally, the commonly reported adverse effects of a saturated solution of potassium iodide (SSKI) are nausea (14%), abdominal pain (14%), metallic taste (4%), and diarrhea (4%) (17561). These side effects can be minimized by avoiding quick dosage increases (17574). Taking iodine chronically or in large amounts has also been reported to cause soreness in teeth and gums, burning in mouth and throat, increased salivation, swelling of parotid and submaxillary glands, inflammation of the respiratory tract, gastric upset, and diarrhea (15,2138).
Intranasally, applying povidone-iodine 1% solution along with a 10% ointment can cause unpleasant nasal tingling (105877).

Immunologic ...People who are allergic to iodine-containing foods or drugs are sometimes stated to have "iodine allergy", but the actual allergen is another agent such as seafood proteins or radiocontrast media (93001). However, some people can be hypersensitive to iodine when used orally. Symptoms of hypersensitivity can include angioedema, cutaneous and mucosal hemorrhage, fever, arthralgia, lymph node enlargement, eosinophilia, urticaria, erythema, and thrombotic thrombocytopenic purpura (15,17561). Other reported side effects include potassium toxicity, metabolic acidosis, pustular psoriasis, and vasculitis (17574). However, such sensitivity is very rare (93001). Orally, iodine hypersensitivity can cause fatal periarteritis (15).

Neurologic/CNS ...Orally, common side effects of a saturated solution of potassium iodide (SSKI) have included headache (7%) (17561). Side effects can be minimized by avoiding quick dosage increases (17574).
High intake of iodine may be associated with adverse cognitive outcomes in children. Observational research in children aged 7-14 years has found that those consuming drinking water with iodine concentrations above 900 mcg/L daily, which exceeds the tolerable upper intake level, is associated with a 1.6-point reduction in intelligence level when compared with those consuming water with iodine concentrations below 300 mcg/L (108709).

Ocular/Otic ...Orally, taking iodine chronically or in large amounts has been reported to cause eye irritation and eyelid swelling (15,2138).

Pulmonary/Respiratory ...Orally, common side effects of a saturated solution of potassium iodide (SSKI) included rhinorrhea (11%) (17561). Side effects can be minimized by avoiding quick dosage increases (17574). Taking iodine chronically or in large amounts has also been reported to cause coryza, sneezing, cough, and pulmonary edema (15,2138). Ophthalmically, povidone-iodine 5% solution 3 drops administered in each eye has been reported to slow respiration by about 18 seconds (range 4 to 96 seconds) when compared with saline control in children ages 2-17 years undergoing strabismus surgery (103077).

Renal ...When povidone-iodine was used in renal pelvic instillation sclerotherapy, one patient (2%) had significant flank pain during treatment (55970).

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General ...Orally, selenium is generally well-tolerated when used in doses that do not exceed the tolerable upper intake level (UL) of 400 mcg daily. Intravenously, selenium is generally well-tolerated.
Most Common Adverse Effects:
Orally: Gastric discomfort, headache, and rash. Excessive amounts can cause alopecia, dermatitis, fatigue, nail changes, nausea and vomiting, and weight loss.
Serious Adverse Effects (Rare):
Orally: Excessive ingestion has led to cases of multi-organ failure and death.

Dermatologic ...Excess selenium can produce selenosis in humans, affecting liver, skin, nails, and hair (74304,74326,74397,74495,90360,113660) as well as dermatitis (74304). Results from the Nutritional Prevention of Cancer Trial conducted among individuals at high risk of nonmelanoma skin cancer demonstrate that selenium supplementation is ineffective at preventing basal cell carcinoma and that it increases the risk of squamous cell carcinoma and total nonmelanoma skin cancer (10687). Mild skin rash has been reported in patients taking up to 200 mcg of selenium daily for up to 12 months (97943).

Endocrine ...Multiple clinical studies have found an association between increased intake of selenium, either in the diet or as a supplement, and the risk for type 2 diabetes (97091,99661). One meta-analysis shows that a selenium plasma level of 90 mcg/L or 140 mcg/L is associated with a 50% or 260% increased risk for developing type 2 diabetes, respectively, when compared with plasma levels below 90 mcg/L. Additionally, consuming selenium in amounts exceeding the recommended dietary allowance (RDA) is associated with an increased risk of developing diabetes when compared with consuming less than the RDA daily. Also, taking selenium 200 mcg daily as a supplement is associated with an 11% increased risk for diabetes when compared with a placebo supplement (99661).
Hypothyroidism, secondary to iodine deficiency, has been reported as a result of selenium intravenous administration (14563,14565). One large human clinical trial suggested a possible increased risk of type 2 diabetes mellitus in the selenium group (16707).

Gastrointestinal ...In human research, nausea, vomiting, and liver dysfunction has been reported as a result of high selenium exposure (74439,74376,113660). Mild gastric discomfort has been reported in patients taking up to 200 mcg of selenium daily for up to 12 months (97943).

Genitourinary ...The effect of selenium supplementation on semen parameters is unclear. In human research, selenium supplementation may reduce sperm motility (9729); however, follow-up research reported no effect on sperm motility or any other semen quality parameter (74441).

Musculoskeletal ...Chronic selenium exposure of 30 mg daily for up to 24 weeks may cause arthralgia, myalgia, and muscle spasms (113660).

Neurologic/CNS ...Chronic exposure to organic and inorganic selenium may cause neurotoxicity, particularly motor neuron degeneration, leading to an increased risk of amyotrophic lateral sclerosis (ALS) (74304). Headache has been reported in patients taking up to 200 mcg of selenium daily for up to 12 months and in patients taking sodium selenate 30 mg daily for up to 24 weeks (97943,113660).

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General ...Adverse reactions have not been reported. However, a thorough evaluation of safety outcomes has not been conducted. There is some concern about contamination with bovine spongiform encephalitis (BSE) (1825). There have been no reports of BSE transfer to humans from contaminated spleen extract products. Until more is known, tell patients to avoid these products unless country of origin can be determined. Patients should avoid products that are produced in countries where BSE has been found.

Other ...Spleen extract is derived from raw animal spleens gathered from slaughterhouses, possibly from sick or diseased animals. Products made from contaminated or diseased organs might present a human health hazard. There is concern that spleen extracts produced from cows in countries where bovine spongiform encephalitis (BSE) has been reported might be contaminated with diseased tissue. Countries where BSE has been reported include Great Britain, France, The Netherlands, Portugal, Luxembourg, Ireland, Switzerland, Oman, and Belgium (1825). There have been no reports of BSE transfer to humans from contaminated spleen extract products. Until more is known, tell patients to avoid these products unless country of origin can be determined. Patients should avoid products that are produced in countries where BSE has been found.

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General ...Orally, thymus extract seems to be well tolerated. No adverse effects have been reported in clinical trials.

Immunologic ...In one case report, severe anaphylactic reaction associated with thymostimulin administration occurred in a 36-year-old male being treated for a neck tumor (78453).

Other ...Thymus extract is derived from raw bovine thymus glands gathered from slaughterhouses, which could include sick or diseased animals (6620). Products made from contaminated or diseased organs might present a human health hazard. However, there are no reports of disease transfer to humans from contaminated thymus extract.
There is also some concern that thymus extract that is obtained from cows in countries where bovine spongiform encephalitis (BSE) has been reported might be unsafe. However, there are no reports of BSE transfer to humans from contaminated thymus extract. Countries where BSE has been reported include Great Britain, France, The Netherlands, Portugal, Luxembourg, Ireland, Switzerland, Oman, and Belgium (1825).

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General ...Orally, thyroid extract may be unsafe due to hormone potency inconsistencies.
Most Common Adverse Effects:
Orally: Elevated levels of triiodothyronine (T3) and/or thyroxine (T4).
Serious Adverse Effects (Rare):
Orally: Thyroid storm or thyrotoxic crisis.

Dermatologic ...In one case report, a teenage female taking thyroid extract developed multiple nevi on the skin (28622). In another case report, a 30-year-old female with allergic rhinitis and multinodular goiter developed allergic urticaria after treatment with desiccated thyroid extract (28619).

Endocrine ...Clinical research shows that many patients treated with thyroid extract experience abnormally high levels of triiodothyronine (T3) and/or thyroxine (T4) (28621,29987,97621). In some patients, these elevated hormone levels result in thyrotoxic crisis or thyroid storm, with symptoms including nausea, vomiting, myalgia, fever, tachycardia, hypertension, agitation, and altered mental state (28621,29987,97621). In one case, a healthy 62-year-old female took a thyroid extract that was accidentally compounded to provide T3 and T4 at levels of 720,000 and 30,000 micrograms, respectively, daily. The patient required plasmapheresis for two days to reduce levels of T3 and T4 and reduce the symptoms of thyroid storm (97621).

Immunologic ...A 30-year-old female with allergic rhinitis and multinodular goiter developed allergic urticaria after treatment with desiccated thyroid extract (28619).

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General ...Orally, tyrosine seems to be well tolerated. No serious adverse effects have been documented; however, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Fatigue, headache, heartburn, and nausea.

Gastrointestinal ...Orally, tyrosine can cause nausea and heartburn when taken at a dose of 150 mg/kg (7211). Taking tyrosine 4 grams daily in combination with 5-hydroxytryptophan 800 mg and carbidopa 100 mg can cause diarrhea, nausea, and vomiting. These effects can be mitigated by lowering the dosage (918).

Musculoskeletal ...Orally, larger doses of tyrosine (150 mg/kg) can cause arthralgia, but this is uncommon (7211).

Neurologic/CNS ...Orally, larger doses of tyrosine (150 mg/kg) can cause headache and fatigue (7211). Taking a combination of tyrosine 4 grams, 5-hydroxytryptophan 800 mg, and carbidopa 100 mg can cause drowsiness and agitation. These effects can be mitigated by lowering the dosage (918).

(Read more about TYROSINE)