tf Age Defying Effects Hydrating Cleanser by 4Life

Alpha hydroxy acids represent a group of natural chemicals that are used alone or in combination. See specific monographs for effectiveness information.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. Although there is interest in using oral or intravenous chelation therapy products for Alzheimer disease, there is insufficient reliable information about the clinical effects of chelation therapy products for this condition.
• Angina. It is unclear if oral or intravenous chelation therapy products are beneficial for angina. Details: A small clinical trial (Program to Assess Alternative Treatment Strategies to Achieve Cardiac Health; PATCH) in patients with angina shows that 500-mL infusions of a multicomponent disodium ethylenediamine tetraacetic acid (EDTA) chelation solution (Endrate) does not improve exercise capacity or time to ischemia when compared with a placebo containing all components other than EDTA. The dose of EDTA was 40 mg/kg (maximum 3 grams per dose) and was provided over a period of 3 hours. Infusions took place twice weekly for 15 weeks and then monthly for 3 months. Each infusion also provided magnesium sulfate 750 mg, ascorbic acid 5 grams, and sodium bicarbonate 5 grams. All patients also took an oral multivitamin/multimineral product (108104). This study may have been underpowered to detect differences between groups. There is currently no information suggesting that the oral use of chelation therapy products is beneficial.
• Arsenic poisoning. Although there is interest in using topical chelation therapy products for arsenic poisoning, there is insufficient reliable information about the clinical effects of topical chelation therapy products for this condition.
• Atherosclerosis. Although there is interest in using oral chelation therapy products for atherosclerosis, there is insufficient reliable information about the clinical effects of chelation therapy products for this condition.
• Attention deficit-hyperactivity disorder (ADHD). Although there is interest in using oral chelation therapy products for ADHD, there is insufficient reliable information about the clinical effects of chelation therapy products for this purpose.
• Atopic disease. Although there is interest in using oral chelation therapy products for atopic disease, there is insufficient reliable information about the clinical effects of chelation therapy products for this purpose.
• Autism spectrum disorder. It is unclear if oral or topical chelation therapy products are beneficial for autism spectrum disorder. Details: Various chelation therapy products have been investigated in clinical research. One preliminary clinical trial in children aged 3-8 years with autism spectrum disorder shows that taking dimercaptosuccinic acid (DMSA) 10 mg/kg three times daily as chelation therapy does not improve sociability, communication with speech or language, or general stereotypical behaviors when compared with placebo. The DMSA was taken for 3 days and then repeated up to 6 times, with 11 days off between treatment periods. Prior to the initiation of this phase of the study, all children received at least one 3-day round of chelation therapy to ensure the excretion of high amounts of heavy metals; however, heavy metal excretion was not compared between groups . Also, half of the children received topical glutathione for 7 days (21057,108099,108109). Other preliminary clinical research in children aged 3-9 years with autism spectrum disorder shows that taking a single dose of DMSA 10 mg/kg increases urinary excretion of cadmium, mercury, and lead. Taking DMSA monthly for 6 months improves overall behavior when compared with baseline. However, only specific behaviors, such as relating to people, imitation, and communication, were improved; other behaviors, including emotional, visual, auditory, or intellectual responses, were not improved (108110). The validity of these findings is limited by the lack of a comparator group. Small clinical studies have also evaluated other chelation therapy products in children with autism spectrum disorder. These include rectal thiamine tetrahydrofurfuryl disulfide (108111) and oral, intravenous, rectal, or topical 2,3-dimercaptopropane-1-sulfonate (DMPS) (108098). However, there is insufficient reliable information available regarding their effects.
• Cancer. Although there is interest in using oral chelation therapy products for cancer, there is insufficient reliable information about the clinical effects of chelation therapy products for this use.
• Cardiovascular disease (CVD). It is unclear if oral or intravenous chelation therapy products are beneficial for CVD. Details: One large clinical study (the Trial to Assess Chelation Therapy; TACT) in adults with stable coronary disease following a recent myocardial infarction (MI) shows that receiving 500-mL infusions of a multicomponent disodium ethylenediamine tetraacetic acid (EDTA) chelation solution, with or without oral high-dose vitamins, reduces the composite risk of total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization by about 18% over 5 years. However, there was no effect of EDTA on the risk of these individual endpoints. A sub-group analysis shows that the risk of this composite outcome is reduced by up to 41% in patients who also have diabetes, with no reduction in patients without diabetes (94983,94985). Also, receiving just the multicomponent disodium EDTA chelation solution without oral high-dose vitamins does not reduce the risk of this composite outcome when compared with placebo, even in the subgroup of patients with diabetes (94986). Each infusion provided EDTA 3 grams over a period of at least 3 hours in combination with ascorbic acid 7 grams, magnesium chloride 2 grams, potassium chloride 2 mEq, sodium bicarbonate 840 mg, pantothenic acid 250 mg, thiamine 100 mg, pyridoxine 100 mg, procaine hydrochloride 100 mg, and heparin 2500 units (94983,94985,94986). Significant limitations of the trial, including missing data and possible unblinding, limit the reliability of these findings (95697).
• Hypertension. Although there is interest in using oral chelation therapy products for hypertension, there is insufficient reliable information about the clinical effects of chelation therapy products for this condition.
• Influenza. Although there is interest in using oral chelation therapy products for influenza, there is insufficient reliable information about the clinical effects of chelation therapy products for this purpose.
• Lead toxicity. Although there is interest in using topical chelation therapy products for lead toxicity, there is insufficient reliable information about the clinical effects of topical chelation therapy products for this condition.
• Mercury toxicity. Although there is interest in topical chelation therapy products for mercury toxicity, there is insufficient reliable information about the clinical effects of topical chelation therapy products for this condition.
• Osteoporosis. Although there is interest in using oral chelation therapy products for osteoporosis, there is insufficient reliable information about the clinical effects of chelation therapy products for this condition.
• Parkinson disease. Although there is interest in using oral chelation therapy products for Parkinson disease, there is insufficient reliable information about the clinical effects of chelation therapy products for this condition.
• Peripheral arterial disease (PAD). It is unclear if oral or intravenous chelation therapy products are beneficial for PAD. Details: Individual preliminary clinical trials included in a systematic review have shown that intravenous disodium ethylenediamine tetraacetic acid (EDTA) has no beneficial effect on blood flow, walking distance, pain-free walking distance, blood lipid levels, or well-being in patients with PAD (5752,5753,5754,108103). Most studies have used EDTA 3 grams twice weekly, usually in combination with vitamins and minerals, over a period of up to 10 weeks (5753,108103). In addition, there is no information suggesting that the oral use of EDTA is beneficial.
• Uterine fibroids. Although there is interest in using oral chelation therapy products for uterine fibroids, there is insufficient reliable information about the clinical effects of chelation therapy products for this purpose. More evidence is needed to rate chelation therapy products for these uses.

(Read more about CHELATION THERAPY PRODUCTS)

EFFECTIVE

• Pantothenic acid deficiency. Taking pantothenic acid 5-10 mg daily is effective for treating and preventing pantothenic acid deficiency (15).

POSSIBLY INEFFECTIVE

• Radiation dermatitis. Topical dexpanthenol does not seem to be beneficial for preventing or treating radiation dermatitis. Details: Applying dexpanthenol, an analog of pantothenic acid, twice daily to areas of irradiated skin does not seem to reduce erythema, desquamation, itching, or pain following radiation treatment (7192). Also, applying dexpanthenol 0.5% cream (Bepanthen, Hoffmann LaRoche ) daily during radiation therapy and for 2 weeks after completing radiation therapy is less effective than methylprednisolone aceponate 0.1% cream (Advantan) at reducing radiation-induced skin irritation (67779).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Oral or topical pantothenic acid has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In adults with mild to moderate acne, clinical research shows that taking a specific supplement (Pantothen, Avilan Marketing LLC) providing pantothenic acid 1.1 grams twice daily in addition to other B vitamins for 12 weeks modestly reduces total and non-inflammatory lesion counts when compared with placebo (105188). Also, in adolescents or young adults with mild to moderate acne, preliminary clinical research shows that topical application with a gel containing D-panthenol 4%, hydrogen peroxide 4%, and salicylic acid 0.5% once daily for 60 days modestly reduces acne lesions when compared with baseline (105189). The validity of this finding is limited by the lack of a comparator group.
• Alcoholism. Although there is interest in using oral pantothenic acid for improving recovery from alcoholism, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Allergic rhinitis (hay fever). Although there is interest in using oral pantothenic acid for allergic rhinitis, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Alopecia areata. Pantothenic acid 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 diffuse hair loss shows that intramuscular administration of dexpanthenol 250 mg and biotin 5 mg once weekly for 6 weeks reduces hair fall count at weeks 1 and 8, but only increases hair density at week 1, when compared to baseline (111366). The validity of these findings is limited by the study's small size, short duration, and lack of comparator group.
• Anxiety. Although there is interest in using oral pantothenic acid for anxiety, there is insufficient reliable information about the clinical effects of pantothenic acid for this purpose.
• Asthma. Although there is interest in using oral pantothenic acid for asthma, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Athletic performance. Although there is interest in using oral pantothenic acid to improve athletic performance, there is insufficient reliable information about the clinical effects of pantothenic acid for this purpose.
• Attention deficit-hyperactivity disorder (ADHD). Oral pantothenic acid has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some small outdated clinical studies in children diagnosed with hyperkinesis suggest that taking calcium pantothenate 1.2 grams, alone or in combination with niacinamide, ascorbic acid, and pyridoxine, does not improve symptoms of hyperactivity when compared with placebo (3351,9957). It is unclear what effects pantothenic may have, if any, in children with a modern diagnosis of ADHD.
• Atopic dermatitis (eczema). It is unclear if topical pantothenic acid is beneficial in infants or children with atopic dermatitis. Details: One preliminary clinical trial in infants and children with stable mild atopic dermatitis shows that topical application of an emollient containing panthenol (Bepanthen, SensiDaily, Bayer Consumer Care AG) for 3 months is as effective as a reference emollient for reducing symptoms and preventing a flare. However, the efficacy of the reference emollient (Stelatopia Emollient Cream, Mustela; Laboratoires Expanscience) is unclear based on available preliminary clinical research (105190).
• Autism spectrum disorder. Although there is interest in using oral pantothenic acid for autism spectrum disorder, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Carpal tunnel syndrome. Although there is interest in using oral pantothenic acid for carpal tunnel syndrome, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Chronic fatigue syndrome (CFS). Although there is interest in using oral pantothenic acid for CFS, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Conjunctivitis. Although there is interest in using oral or ocular pantothenic acid for conjunctivitis, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Constipation. It is unclear if oral or intramuscular dexpanthenol is beneficial for constipation. Details: Preliminary clinical research shows that administering dexpanthenol (Bepanthene), an analog of pantothenic acid, 400 mg orally or 500 mg intramuscularly daily for 5 days decreases the time to a bowel movement in patients with chronic or occasional constipation when compared with an oral placebo (67822).
• Dandruff. Although there is interest in using oral or topical pantothenic acid for dandruff, is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Depression. Although there is interest in using oral pantothenic acid for depression, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Diaper rash. Although there is interest in using topical pantothenic acid for diaper rash, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Dry eye. Although there is interest in using ocular pantothenic acid for dry eye, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Dry skin. It is unclear if topical dexpanthenol is beneficial for patients with dry skin. Details: A small, open-label study in healthy adults with dry skin shows that cleansing the skin with a dexpanthenol-containing liquid cleanser (DCLC, Bepanthen SensiControl Daily Gentle Body Wash) daily for 4 weeks increases stratum corneum hydration by 17% without affecting skin barrier function, pH, or microbiome when compared to baseline (111262). The validity of these findings is limited by the lack of blinding and a comparator group.
• Epilepsy. Although there is interest in using oral pantothenic acid for epilepsy, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Eye trauma. It is unclear if ocular dexpanthenol is beneficial for eye trauma. Details: Some preliminary clinical research shows that using eyedrops containing dexpanthenol 5%, a derivative of pantothenic acid, two drops four times daily for 28 days following surgery for retinal detachment reduces eye pain and discomfort when compared with placebo drops (67783). However, using a specific dexpanthenol 5% ointment (Bepanthen) does not seem to improve corneal epithelial wound healing following phototherapeutic keratectomy when compared with placebo (67801).
• Heart failure. Although there is interest in using oral pantothenic acid for heart failure, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Herpes zoster (shingles). Although there is interest in using oral or topical pantothenic acid for shingles, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Insomnia. Although there is interest in using oral pantothenic acid for insomnia, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Laser skin resurfacing. It is unclear if topical dexpanthenol or pantothenic acid can reduce adverse effects after laser skin resurfacing procedures. Details: A preliminary clinical study shows that use of a dexpanthenol-containing ointment (Bepanthen Wound Healing Ointment, Bayer) once daily modestly reduces the diameter of lesions up to 3 days after fractional carbon dioxide laser resurfacing when compared with petroleum jelly (105743). Also, applying a specific cream (Cicaplast Baume B5 cream, L'Oreal) containing panthenol 5%, madecassoside, copper, zinc, and manganese to one side of the face for 28 days reduces decrustation time by approximately one day when compared with a control emollient. Redness and swelling were lower at 3 days, but there was no difference in pain and burning (105742). It is unclear if these effects are due to pantothenic acid, other ingredients, or the combination.
• Multiple sclerosis (MS). Although there is interest in using oral pantothenic acid for MS, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Muscular dystrophy. Although there is interest in using oral pantothenic acid for muscular dystrophy, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Nipple fissures. Although there is interest in using topical pantothenic acid for nipple fissures, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Obesity. Although there is interest in using oral pantothenic acid for obesity, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Pain (chronic). It is unclear if oral or topical pantothenic acid is beneficial for the management of various forms of chronic pain. Details: Although there is interest in using oral or topical pantothenic acid for various forms of chronic pain, including neuropathy and arthritis, there is limited information available about the clinical effects of pantothenic acid for this purpose. One review of preliminary clinical research found that calcium pantothenate does not reduce symptoms of arthritis in patients with rheumatoid arthritis or osteoarthritis (10433).
• Parkinson disease. Although there is interest in using oral pantothenic acid for Parkinson disease, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Poison oak and poison ivy dermatitis. Although there is interest in using topical pantothenic acid for poison ivy dermatitis, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Postoperative pain. It is unclear if oral pantothenic acid is beneficial for postoperative pain. Details: In post-tonsillectomy patients aged 5-12 years, preliminary clinical research shows that taking pastilles containing dexpanthenol (Bepanthene, Bayer) 100 mg three times daily reduces pain when compared with placebo. Postoperative pain was modestly reduced at 1, 3, 7, and 14 days after surgery (105191).
• Postoperative sore throat. It is unclear if pantothenic acid lozenges are beneficial for postoperative sore throat. Details: Preliminary clinical research shows that taking two lozenges containing dexpanthenol, an analog of pantothenic acid, 200 mg 30 minutes prior to general anesthesia reduces the incidence and severity of postoperative sore throat when compared with a benzydamine hydrochloride or placebo spray (67792).
• Pregnancy-related leg cramps. Although there is interest in using oral pantothenic acid for pregnancy-related leg cramps, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Premenstrual syndrome (PMS). Although there is interest in using oral pantothenic acid for PMS, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Respiratory tract infections. Although there is interest in using oral pantothenic acid for respiratory tract infections, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Rhinosinusitis. It is unclear if nasal dexpanthenol is beneficial for rhinosinusitis. Details: Preliminary clinical research shows that using a nasal spray (MarPlus) containing dexpanthenol, an analog of pantothenic acid, on the first, second, fourth, and sixth week after endoscopic sinus surgery reduces nasal discharge, but not other symptoms associated with chronic rhinosinusitis, when compared with saline nasal spray (67808).
• Skin irritation. It is unclear if topical dexpanthenol is beneficial for preventing or treating skin irritation due to sodium lauryl sulfate. Details: Preliminary clinical research shows that applying dexpanthenol (Bepanthol Handbalsam), an analog of pantothenic acid, twice daily for 26 days does not prevent sodium lauryl sulfate-induced skin irritation (67785). However, dexpanthenol may be effective for treating skin irritation caused by sodium lauryl sulfate. Use of an ointment containing dexpanthenol 1% to 5% twice daily for up to 30 days following skin exposure to sodium lauryl sulfate seems to reduce skin water loss, skin roughness, and skin inflammation when compared to control (67802,67806).
• Ulcerative colitis. Although there is interest in using oral or rectal pantothenic acid for ulcerative colitis, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Vertigo. Although there is interest in using oral pantothenic acid for vertigo, there is insufficient reliable information about the clinical effects of pantothenic acid for this condition.
• Wound healing. Preliminary clinical research suggests that oral dexpanthenol might be beneficial for wound healing. Details: In post-tonsillectomy patients aged 5-12 years, preliminary clinical research shows that taking pastilles containing dexpanthenol (Bepanthene, Bayer) 100 mg three times daily improves wound healing when compared with placebo. Depending on the type of surgery, wound healing occurred in 2.3-2.9 times as many patients within 7 days of surgery, and in 13% to 35% more patients within 14 days, when compared with placebo (105191). More evidence is needed to rate pantothenic acid for these uses.

(Read more about PANTOTHENIC ACID)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Asthma. It is unclear if dietary citrus fruits are beneficial in patients with asthma. Details: There is some evidence that consumption of vitamin C-rich citrus fruits, including sweet orange and others, might improve lung function in people with asthma. However, this is controversial. Some studies show that intake of citrus fruits 1-2 times per week produces significant benefit (6049,6055,6056), while other studies have not found this benefit (6057,6058).
• Common cold. It is unclear if drinking sweet orange juice prevents the common cold. Details: Preliminary clinical research in healthy individuals ages 17 to 25 years suggests that drinking sweet orange juice 180 mL daily for 72 days might decrease the risk of developing common cold-related symptoms (15328).
• Depression. It is unclear if drinking sweet orange juice or using sweet orange essential oil as aromatherapy is beneficial for depression. Details: Preliminary clinical research in adults with depression shows that drinking flavonoid-rich sweet orange juice 190 mL three times daily for 8 weeks modestly improves depression scores when compared to baseline, but not when compared with a low-flavonoid orange drink (110045). Sweet orange has also been studied as part of a combination aromatherapy. A very small clinical study in community-dwelling older adults shows that massage therapy to the upper body with sweet orange, lavender, and bergamot oils twice weekly for 8 weeks improves symptoms of depression in 65% of patients when compared with no intervention. Twice weekly inhalation of the same essential oils via nebulizer, without massage, also improves symptoms of depression in 55% of patients when compared with no intervention (98474).
• Hypercholesterolemia. It is unclear if drinking sweet orange juice improves blood lipid levels. Details: A very small clinical study in hypercholesterolemic patients shows that drinking large amounts of sweet orange juice (750 mL daily for four weeks) seems to increase high-density lipoprotein (HDL) cholesterol by 21% and reduce the ratio of low-density lipoprotein (LDL) to HDL cholesterol by 16% when compared to baseline. This effect was not seen with 250-500 mL of sweet orange juice. Because consumption of this large amount of juice daily provides approximately 20% of the daily energy requirement, this regimen may not be practical (3340).
• Insomnia. Sweet orange essential oil as aromatherapy has only been evaluated in combination with other essential oils; its effect when used alone is unclear. Details: Preliminary clinical research in adults undergoing hemodialysis shows that inhaling aromatherapy with sweet orange and lavender oil nightly before bed for one month improves overall sleep quality by 72% and fatigue by about 78% when compared with no treatment (98508).
• Kidney failure. It is unclear if sweet orange oil massage can improve fatigue or symptoms of restless leg syndrome (RLS) in adults receiving hemodialysis. Details: A small clinical study shows that receiving an 18-minute foot massage with sweet orange oil 1.5% for 3 weeks during hemodialysis sessions modestly improves sleep quality and symptoms of RLS when compared with routine care. However, it does not seem to be more effective than using lavender oil (109859).
• Kidney stones (nephrolithiasis). It is unclear if drinking sweet orange juice is beneficial for preventing kidney stones. Details: Consuming 400 mL of sweet orange juice three times a day, providing a total of 100 mEq of citrate daily, increases urinary pH and urinary citrate levels (15171). Theoretically, this might reduce kidney stone formation in patients with calcium nephrolithiasis. However, this outcome has not been evaluated in clinical research.
• Obesity. It is unclear if drinking sweet orange juice or taking oral sweet orange extract improves weight loss or other metabolic parameters in adults with overweight or obesity. Most studies suggest that any effects are unlikely to be considered clinically relevant. Details: Some preliminary clinical research in adults with overweight or obesity shows that taking a specific sweet orange extract (Morosil, Bionap S.R.L.) 400 mg orally once daily for six months reduces waist circumference, body weight, fat mass, and body mass index (BMI) by 2% to 5% when compared with placebo (110046). However, other preliminary clinical research in this population shows that drinking red sweet orange juice 750 mL daily for 8 weeks does not reduce body weight or BMI when compared with baseline (92309). A meta-analysis of clinical research in adults, most of whom were overweight or obese at baseline, shows that drinking 250-750 mL of various types of sweet orange juice daily for 2-12 weeks does not reduce body weight, BMI, waist circumference, or body fat percentage (BFP) when compared with control groups, which included either no supplementation, pomegranate juice, or exercise (107853). The validity of this meta-analysis is limited due to the population heterogeneity and variety of orange juice formulations and controls utilized. Some clinical studies have also evaluated sweet orange juice for improving cardiovascular risk factors in overweight and obese adults. Although some research has shown benefit, not all research agrees (110046,110047). A meta-analysis of randomized clinical trials in adults with overweight or obesity shows that drinking sweet orange juice 250-600 mL daily for 2-13 weeks modestly increases high-density lipoprotein cholesterol levels and decrease average systolic blood pressure by 1 mmHg when compared with control. However, drinking sweet orange juice does not affect other blood lipid levels, blood glucose levels, or markers of insulin resistance (110048). The validity of this study is limited by high heterogeneity and a small sample size. In addition, these improvements are unlikely to be considered clinically relevant. Sweet orange extract has also been studied in combination with other ingredients. Some clinical research in overweight adults shows that taking a specific combination product (Sinetrol, Fytexia) 450-700 mg twice daily containing sweet orange, blood orange, and grapefruit extracts for 12 weeks reduces body weight, BFP, and BMI when compared with placebo or baseline (95517,95518). It is unclear if these effects are due to sweet orange, other ingredients, or the combination.
• Pre-procedural anxiety. It is unclear if inhaling sweet orange essential oil as aromatherapy reduces anxiety before surgeries or invasive procedures. Details: A small, low-quality study suggests that inhaling the scent from 3 drops of sweet orange essential oil applied to a cotton ball for 5 minutes modesty reduces anxiety and pain scores in patients undergoing needle insertion for hemodialysis when compared with performing a breathing exercise for 3 minutes (105455).
• Prostate cancer. It is unclear if drinking sweet orange juice reduces prostate cancer risk. Details: Observational research has found that increasing dietary intake of sweet orange or sweet orange juice is not associated with a reduced risk of developing prostate cancer (15172).
• Stress. It is unclear if inhaling sweet orange essential oil as aromatherapy is beneficial for stress. Details: Preliminary clinical research shows that using up to 10 drops of sweet orange essential oil as aromatherapy helps prevent some anxiety and tension associated with stressful tasks when compared with control (90505). More evidence is needed to rate sweet orange for these uses.

(Read more about SWEET ORANGE)

POSSIBLY EFFECTIVE

• Herpes zoster (shingles). Administering transfer factor subcutaneously seems to prevent varicella-zoster in children with leukemia. A single subcutaneous treatment with human-derived transfer factor prepared from donors with varicella-zoster antibodies seems to almost completely protect nonimmune children with acute lymphocytic leukemia against varicella-zoster infection (384). However, the same treatment does not seem to prevent recurrent varicella-zoster infection or restore immunity in people receiving bone marrow transplant for leukemia (3278). In addition to having a prophylactic effect, some preliminary clinical evidence suggests that human-derived transfer factor may help treat herpes zoster. Administering human-derived transfer factor subcutaneously seems to reduce the duration of pain by about 5 days compared to treatment with acyclovir in patients with acute-stage herpes zoster infection (78842).

POSSIBLY INEFFECTIVE

• Lung cancer. Most research shows that administering human-derived transfer factor intramuscularly or subcutaneously, in combination with lung resection and chemotherapy, does not increase survival in patients with lung cancer (5447,7800,78793). However, some preliminary evidence suggests that transfer factor might improve survival in lung cancer patients with Stage IIIA or IIIB disease (78824).
• Melanoma. Administering human-derived transfer factor intramuscularly or subcutaneously, as adjuvant therapy, does not seem to affect disease progression or prolong survival when used for up to 2 years following surgery for Stage I and Stage II melanoma (3062,3063,78691).
• Multiple sclerosis (MS). Most research suggests that transfer factor given subcutaneously does not improve disease progression in people with MS (7799,78670,78796). While some research suggests that transfer factor might slow disease progression in people with mild to moderate symptoms, a positive effect is seen only after 18 months to 2 years of therapy (7798).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Preliminary clinical research suggests that subcutaneous injection of whole or fractionated human-derived transfer factor once weekly for 2 weeks does not improve acne in patients with acne vulgaris (78677).
• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). Preliminary clinical research shows that once monthly injections with human-derived transfer factor from healthy donors does not affect the course of ALS (78751).
• Cervical cancer. Preliminary clinical research suggests that administering transfer factor subcutaneously, once monthly for 2 years, significantly reduces the risk of recurrence after surgery and irradiation compared to placebo in patients with invasive cervical cancer (78693).
• Chronic fatigue syndrome (CFS). Transfer factor, obtained from relatives or other human donors, does not seem to improve CFS symptoms when administered intramuscularly biweekly, either alone or in combination with cognitive behavioral therapy (7562). However, some preliminary clinical evidence suggests that taking transfer factor orally improves symptoms in some patients with CFS (78820).
• Crohn disease. Preliminary clinical research suggests that administering transfer factor intramuscularly does not improve clinical condition compared to placebo in patients with Crohn's disease (78712).
• Genital herpes. One preliminary clinical study in patients with recurrent genital herpes shows that taking herpes simplex virus (HSV)-specific transfer factor orally reduces relapse indices from 56.3 to 28.2 compared to baseline (78817). Another preliminary clinical study in patients with severe recurrent genital herpes or other recurrent herpes infections shows that receiving transfer factor subcutaneously may reduce the frequency or severity of recurrence in some patients (78818).
• Hepatitis B. Some preliminary clinical evidence suggests that transfer factor derived from patients with acute hepatitis B, given intramuscularly, might be useful for treating chronic active hepatitis B infection (7797). Other preliminary clinical research shows that transfer factor derived from patients with acute hepatitis B, given subcutaneously, does not improve biochemical parameters in patients with chronic active hepatitis B infection (78775).
• Herpes keratitis. Results from several small clinical trials suggest that transfer factor might reduce the risk of herpes keratitis relapse (78803,78816).
• Herpes labialis (cold sores). One preliminary clinical study in patients with recurrent herpes labialis shows that taking herpes simplex virus (HSV)-specific transfer factor orally reduces relapse indices from 68.7 to 12.9 compared to baseline (78817). Another preliminary clinical study in patients with severe recurrent herpes labials or other recurrent herpes infections shows that receiving transfer factor subcutaneously may reduce the frequency or severity of recurrence in some patients (78818).
• HIV/AIDS. Preliminary clinical research shows that taking HIV-1-specific transfer factor orally for 15 days and then once weekly for 6 months along with zidovudine is no more effective than zidovudine alone for improving hematological parameters and clinical progression in HIV-1 infected patients with asymptomatic disease, persistent generalized lymphadenopathy, or AIDS-related complex (78814).
• Hodgkin lymphoma. Preliminary clinical research shows that administering transfer factor subcutaneously once every 3 months for 21 months does not reduce the incidence of infections compared to placebo in patients with Hodgkin lymphoma (78683).
• Human papillomavirus (HPV). Preliminary clinical research shows that taking transfer factor orally every 72 hours for 4 weeks resolves symptoms in 90% of women and results in normal colposcopy images in 89% of women with chronic cervicitis due to HPV infection. Women taking the placebo had no improvement in symptoms (97664). Other preliminary clinical research shows that taking transfer factor orally for 5 weeks, while also using it topically every 72 hours for the first 2 weeks, repeating every 3 months if a persistent lesion was found, at least doubles the number of patients free of cervical lesions related to HPV infection after 2 years when compared to treatment with cryo- or electro-surgery (97665). However, transfer factor given subcutaneously does not seem to improve wart regression in patients with HPV (78621).
• Intestinal parasite infection. There is some preliminary evidence that oral transfer factor weekly for up to 3 months might be beneficial for people with cryptosporidiosis related to AIDS. Transfer factor from bovine sources seems to improve stool frequency and help eradicate oocysts in some patients (1445,1480).
• Leishmania lesions. There is some evidence that transfer factor obtained from patients with antibodies to leishmania can heal persistent cutaneous leishmania lesions (3930,8105).
• Leukemia. Preliminary clinical research shows that administering transfer factor subcutaneously reduces time to neutrophil and leukocyte count recovery compared to control in patients with acute leukemia (78809).
• Mycosis fungoides. Preliminary clinical research shows that administering transfer factor intramuscularly once weekly for one year does not improve clinical status compared to placebo in patients with mycosis fungoides (78789).
• Nasopharyngeal cancer. There is conflicting evidence about the effects of using transfer factor for nasopharyngeal carcinoma. One case report suggests that administering transfer factor with specific activity against Epstein-Barr virus intramuscularly improves survival in patients with nasopharyngeal carcinoma, while other research shows that it does not (78680,78823).
• Osteosarcoma. Preliminary clinical research suggests that administering human-derived transfer factor subcutaneously does not reduce tumor recurrence or improve survival in patients with resected, nonmetastatic osteosarcoma (78701).
• Prostate cancer. Preliminary clinical evidence suggests that 2-5 units of transfer factor, given intramuscularly once monthly, might improve disease progression in patients with hormone-resistant, metastatic prostate cancer (78825).
• Rheumatoid arthritis (RA). Preliminary clinical research suggests that transfer factor, given subcutaneously, does not provide therapeutic benefit to patients with juvenile rheumatoid arthritis (78702). More evidence is needed to rate transfer factor for these uses.

(Read more about TRANSFER FACTOR)

Some alpha hydroxy acids are used topically, while others are used orally, intravaginally, or by inhalation. See specific monographs for safety information.

PREGNANCY AND LACTATION:
See specific monographs for safety information.

(Read more about ALPHA HYDROXY ACIDS (AHAs))

POSSIBLY UNSAFE ...when unregulated chelation therapy products are used orally or parentally or when prescription chelation therapy products are used for unproven indications and/or in unapproved doses or routes of administration. The American College of Medical Toxicology and The American Academy of Clinical Toxicology recommend against the unapproved use of chelation therapy products (108106). Chelation therapy products can result in severe side effects including dehydration, hypocalcemia, kidney failure, neurodevelopmental toxicity, and death (107700,108095,108096,108105,108106,108107). Also, infusion of the disodium form of EDTA over less than 3 hours can cause severe, life-threatening adverse effects including hypocalcemia and death (5737).

CHILDREN: POSSIBLY UNSAFE
when unregulated chelation therapy products are used orally or parentally or when prescription chelation therapy products are used for unproven indications and/or in unapproved doses or routes of administration. The American College of Medical Toxicology and The American Academy of Clinical Toxicology recommend against the unapproved use of chelation therapy products (108106). Chelation therapy products can result in severe side effects including dehydration, hypocalcemia, kidney failure, neurodevelopmental toxicity, and death (107700,108095,108096,108105,108106,108107).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when unregulated chelation therapy products are used orally or parentally or when prescription chelation therapy products are used for unproven indications and/or in unapproved doses or routes of administration. The American College of Medical Toxicology and The American Academy of Clinical Toxicology recommend against the unapproved use of chelation therapy products (108106). Chelation therapy products can have teratogenic effects and result in severe side effects including dehydration, hypocalcemia, kidney failure, neurodevelopmental toxicity, and death (107700,108095,108096,108105,108106,108107).

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LIKELY SAFE ...when used orally and appropriately. The pantothenic acid derivative calcium pantothenate has a generally recognized as safe (GRAS) status for use in food products (111258). While a tolerable upper intake level (UL) has not been established, pantothenic has been used in doses of 10-20 grams daily with apparent safety (15,6243,111258) ...when applied topically and appropriately, short-term. The Cosmetic Ingredient Review Expert Panel has concluded that pantothenic acid and its derivatives are safe for use in cosmetic products in concentrations up to 5.3% (111258). Gels or ointments containing a derivative of pantothenic acid, dexpanthenol, at concentrations of up to 5%, have been used safely for up to 30 days (67802,67806,67817).

POSSIBLY SAFE ...when applied intranasally and appropriately, short-term. A dexpanthenol nasal spray has been used with apparent safety up to four times daily for 4 weeks (67826). ...when applied in the eyes appropriately, short-term. Dexpanthenol 5% eyedrops have been used with apparent safety for up to 28 days (67783). ...when injected intramuscularly and appropriately, short-term. Intramuscular injections of dexpanthenol 500 mg daily for up to 5 days or 250 mg weekly for up to 6 weeks have been used with apparent safety (67822,111366).

CHILDREN: LIKELY SAFE
when used orally and appropriately (15,6243). Calcium pantothenate is generally recognized as safe (GRAS) when used as a food additive and in infant formula (111258). However, a tolerable upper intake level (UL) has not been established (15,6243). ...when applied topically and appropriately (67795,105190,111262). Infant products containing pantothenic acid and its derivatives have been used safely in concentrations of up to 5% for infant shampoos and 2.5% for infant lotions and oils. The Cosmetic Ingredient Review Expert Panel has concluded that pantothenic acid and derivatives are safe for use in topical infant products. (111258).

PREGNANCY: LIKELY SAFE
when used orally and appropriately. The daily adequate intake (AI) during pregnancy is 6 mg (3094).

LACTATION: LIKELY SAFE
when used orally and appropriately. The daily adequate intake (AI) during lactation is 7 mg (3094).

(Read more about PANTOTHENIC ACID)

LIKELY SAFE ...when sweet orange juice or fruit is used orally in amounts commonly found in foods (1310,3340,15171,92309).

POSSIBLY SAFE ...when the essential oil of sweet orange is inhaled as aromatherapy, short-term (35735,58060,90505,105455). There is insufficient reliable information available about the safety of sweet orange peel when used orally.

CHILDREN: LIKELY SAFE
when sweet orange juice or fruit is used orally in amounts commonly found in foods.

CHILDREN: POSSIBLY UNSAFE
when the sweet orange peel is used orally in excessive amounts. There have been reports of intestinal colic, convulsions, and death in children given large amounts of sweet orange peel (11).

PREGNANCY AND LACTATION: LIKELY SAFE
when sweet orange juice or fruit is used orally in amounts commonly found in foods (1310,3340).

(Read more about SWEET ORANGE)

POSSIBLY SAFE ...when used orally or parenterally and appropriately. Human-derived transfer factor has been used safely in studies lasting up to 2 years (3062,7562,7797,7798) and bovine-derived transfer factor has been safely used in small studies lasting up to 3 months (1445,1507). Some evidence suggests these products are safe; however, some preparations are derived from animals and there is concern about contamination with diseased animal parts (see Adverse Reactions) (1825). There are no reports of disease transmission to humans due to use of contaminated bovine transfer factor.

CHILDREN: POSSIBLY SAFE
when used orally or parenterally and appropriately. Human-derived transfer factor administered subcutaneously has been used safely for up to 6 years (7794). Oral bovine transfer factor has been used safely for up to 6 months (350).

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

(Read more about TRANSFER FACTOR)

(Read more about ALPHA HYDROXY ACIDS (AHAs))

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Concomitant use of ethylenediamine tetraacetic acid (EDTA) and potassium-depleting diuretics might increase the risk for hypokalemia.  Details EDTA can decrease serum potassium levels and increase excretion of potassium (15).

INSULIN Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B Ethylenediamine tetraacetic acid (EDTA) can decrease the activity of insulin and increase the risk for hypoglycemia.  Details Concomitant use of disodium EDTA with insulin can cause severe decreases in blood glucose concentrations (5737,5771). Additionally, EDTA chelates zinc in insulin products (15) and might interfere with the onset and duration of activity of various insulin preparations.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, disodium ethylenediamine tetraacetic acid (EDTA) can decrease the anticoagulant effects of warfarin.  Details Disodium EDTA has been reported to decrease international normalized ratio (INR) in a patient taking warfarin (4611).

(Read more about CHELATION THERAPY PRODUCTS)

(Read more about PANTOTHENIC ACID)

CELIPROLOL (Celicard) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B Consuming sweet orange with celiprolol can decrease oral absorption of celiprolol.  Details A pharmacokinetic study in healthy volunteers shows that celiprolol levels, after a single dose of 100 mg, are decreased by up to 90% in people who drink sweet orange juice 200 mL three times daily. It's not known if lower consumption of sweet orange juice will have the same effect. Theoretically, this occurs due to short-term inhibition of organic anion transporting polypeptide (OATP) (12115,17603,17604). Recommend separating drug administration and consumption of sweet orange by at least 4 hours (17603,17604).

FEXOFENADINE (Allegra) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Likely •  Level of Evidence = B Consuming sweet orange juice with fexofenadine can decrease oral absorption of fexofenadine.  Details Clinical research shows that coadministration of sweet orange juice 1200 mL decreases bioavailability of fexofenadine by about 72% (7046,17604). In an animal model, sweet orange juice decreased bioavailability of fexofenadine by 31% (17605). Fexofenadine manufacturer data indicates that concomitant administration of sweet orange juice and fexofenadine results in larger wheal and flare sizes in research models. This suggests that sweet orange reduces the clinical response to fexofenadine (17603). Theoretically, this occurs due to short-term inhibition of organic anion transporting polypeptide (OATP) (7046). Recommend separating drug administration and consumption of sweet orange by at least 4 hours (17603,17604).

IVERMECTIN (Stromectol, others) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B Consuming sweet orange juice with ivermectin can decrease the oral absorption of ivermectin.  Details A pharmacokinetic study in healthy volunteers shows that taking ivermectin orally with sweet orange juice 750 mL over 4 hours reduces the bioavailability of ivermectin. This effect does not seem to be related to effects on P-glycoprotein. The effect on ivermectin is more pronounced in males compared to females (12154).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B Consuming sweet orange juice can decrease oral absorption of OATP substrates. Separate administration by at least 4 hours.  Details Clinical research shows that consuming sweet orange juice inhibits OATP, which reduces bioavailability of oral drugs that are substrates of OATP (17603,17604). For example, sweet orange juice decreases bioavailability of fexofenadine, a substrate of OATP, by about 72% and of celiprolol, another OATP substrate, by up to 90% (7046,12115). Since sweet orange juice seems to affect OATP for a short time, recommend separating drug administration and consumption of sweet orange juice by at least 4 hours (17603,17604).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Sweet orange juice seems to modulate P-glycoprotein (P-gp), which might affect the blood levels of P-gp substrates.  Details Animal and in vitro research suggest that orange juice extract inhibits drug efflux by P-gp, increasing absorption and levels of P-gp substrates (12116,15327). In contrast, pharmacokinetic research in humans shows that drinking large amounts of sweet orange juice decreases absorption and levels of the P-gp substrate celiprolol. This suggests that orange juice actually induces drug efflux by P-gp or affects drug levels by another mechanism such as inhibiting the gut drug transporter called organic anion transporting polypeptide (OATP) (7046,12115). Until more is known, sweet orange juice should be used cautiously in people taking P-gp substrates.

PRAVASTATIN (Pravachol) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = B Consuming sweet orange juice with pravastatin can increase the absorption of pravastatin.  Details A small pharmacokinetic study in healthy volunteers shows that consuming sweet orange juice 800 mL over 3 hours, including before, during, and after taking pravastatin 10 mg, increases pravastatin levels by about 149%, without affecting pravastatin elimination. Theoretically this effect might be due to modulation of organic anion transporting polypeptides (OATPs) by sweet orange juice (14348). Sweet orange juice does not seem to affect simvastatin levels, but it is not known if sweet orange affects any of the other statins.

QUINOLONE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Calcium-fortified sweet orange juice might reduce quinolone absorption.  Details Calcium binds to quinolones in the gut. Theoretically, the calcium in certain fortified orange juices can also bind to quinolone antibiotics and reduce their absorption and levels (4412,10339,13714,21638,38570).

(Read more about SWEET ORANGE)

(Read more about TRANSFER FACTOR)

General ...Alpha hydroxy acids represent a group of natural chemicals, some of which can cause adverse effects. See specific monographs for safety information.

(Read more about ALPHA HYDROXY ACIDS (AHAs))

General ...The use of chelation therapy products for unproven indications, or in unapproved doses or routes of administration, is generally considered to be unsafe.
Most Common Adverse Effects:
Orally: Gastrointestinal upset, nausea.
Intravenous: Abdominal cramps, anorexia, burning and pain at infusion site, diarrhea, headache, nausea, vomiting.
Serious Adverse Effects (Rare):
Orally: Allergic reactions, Stevens-Johnson syndrome.
Intravenous: Allergic reactions, arrhythmias, convulsions, death, heart failure, hypercalcemia, hypocalcemia, insulin shock, kidney failure, paresthesia, respiratory arrest, tetany, thrombophlebitis.

Cardiovascular ...Intravenously, chelation therapy products such as 2,3-dimercaptopropane-1-sulfonate (DMPS) or ethylenediamene tetraacetic acid (EDTA) have been associated with hypotension and irregular heartbeat (5737,5771,5772,108105,108106). Intravenously, EDTA can also cause thrombophlebitis (108099,108103). Disodium EDTA, when given as a rapid infusion or highly concentrated solution, can cause hypocalcemia, severe cardiac arrhythmias, respiratory arrest, and death (15,108102).
There are at least three case reports of intravenous chelation therapy-related hypocalcemia resulting in cardiac arrest. Two cases involved the use of disodium EDTA in children and one involved the unapproved use of an unknown type of EDTA over a 10- to 15-minute infusion in an adult (107700,108095,108096,108097,108105). At least in part because of these cases, disodium EDTA is no longer FDA-approved (108105). In a large clinical trial in patients with a previous myocardial infarction, the rate of hypocalcemia was 6.2% in patients given disodium EDTA, compared with 3.5% of those given placebo; however, disodium EDTA did not increase the risk of heart failure or death (94985).

Dermatologic ...There is a case report of Stevens-Johnson syndrome after two weeks of oral 2,3-dimercaptopropane-1-sulfonate (DMPS) chelation therapy in a child with chronic mercury exposure. Symptoms included a widespread eruption of red, itchy macules which gradually improved after discontinuation of DMPS therapy (108112). Rash has also been reported in patients given intravenous DMPS or oral dimercaptosuccinic acid (DMSA) (108099).
Intravenously, ethylenediamene tetraacetic acid (EDTA) can commonly cause exfoliative dermatitis (15,108103) and a burning sensation and pain at the site of infusion (5744,108103).

Endocrine ...Intravenously, calcium disodium ethylenediamene tetraacetic acid (EDTA) can cause zinc deficiency (5771,5772) and hypercalcemia (5771,5772). Disodium EDTA can occasionally reduce magnesium and potassium serum concentrations (5771,5772), and rarely cause insulin shock (5737).
Disodium EDTA, when given as a rapid infusion or highly concentrated solution, can cause hypocalcemia, leading to tetany, convulsions, cardiac arrhythmias, cardiac failure, respiratory arrest, and death. This has occasionally occurred when the disodium form of EDTA was used in error, instead of the calcium disodium form (15,94984,94985,107700,108095,108096,108097,108099,108105).

Gastrointestinal ...Intravenously, ethylenediamene tetraacetic acid (EDTA) can commonly cause abdominal cramps, anorexia, nausea, vomiting, and diarrhea (15). EDTA can also sometimes cause thirst (15).
When given orally or intravenously, 2,3-dimercaptopropane-1-sulfonate (DMPS) has caused nausea and dysgeusia.
Orally, dimercaptosuccinic acid (DMSA) has caused gastrointestinal upset and diminished appetite (108099).

Hematologic ...Intravenously, ethylenediamene tetraacetic acid (EDTA) can sometimes cause anemia (15), prolonged prothrombin time (5737) and transient bone marrow suppression (5737,5772).

Hepatic ...Intravenously, the calcium disodium form of ethylenediamene tetraacetic acid (EDTA) can cause mild elevations of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and decreased alkaline phosphatase (ALP) levels (15,108102).
Orally, dimercaptosuccinic acid (DMSA) has been associated with mild elevations in liver transaminase levels (108105).

Immunologic ...Intravenously, disodium ethylenediamene tetraacetic acid (EDTA) can rarely cause histamine-like reactions (5737). There are rare reports of allergic reactions to EDTA given as a nasal provocation, topically, intradermally, and subcutaneously (94992). In one case report, a 57-year-old male presented with pruritus on the hands and feet, as well as urticaria and swelling of the face, following subcutaneous injection with a local anesthetic containing EDTA. Allergy to other ingredients in the anesthetic was ruled out, and intradermal and subcutaneous testing with calcium disodium EDTA confirmed the allergic response. The patient also reacted to radio-contrast medium containing EDTA (94992).
Topically, application of EDTA in cosmetics, shampoos, and other products has rarely been reported to cause contact dermatitis (94992).
Orally, dimercaptosuccinic acid (DMSA) has been associated with allergic reactions (108105).

Musculoskeletal ...Intravenously, disodium ethylenediamene tetraacetic acid (EDTA) can occasionally cause muscle cramps, back pains, muscle weakness, and myalgias (15). In a large clinical trial in patients with a previous myocardial infarction, the rate of hypocalcemia was 6.2% in patients given disodium EDTA, compared with 3.5% of those given placebo; however, only one patient had associated muscle cramping leading to a hospital visit (94985).

Neurologic/CNS ...Intravenously, ethylenediamene tetraacetic acid (EDTA) can commonly cause headache and faintness (15,108103). EDTA can also sometimes cause fever, chills, fatigue, and malaise (15,108099). Disodium EDTA can occasionally cause tremors, tingling, and paresthesias (15).
Orally, dimercaptosuccinic acid (DMSA) was associated with lethargy in one child in a clinical trial. Other possible adverse effects associated with DMSA included sleep problems (108099).

Pulmonary/Respiratory ...Intravenously, ethylenediamene tetraacetic acid (EDTA) can sometimes increase sneezing and nasal congestion (15). Inhalation of disodium EDTA contained in nebulizer solutions has been reported to cause dose-related bronchoconstriction (5765).

Renal ...Intravenously, ethylenediamene tetraacetic acid (EDTA) can sometimes cause urinary urgency and frequency (5772). However, the most serious adverse effect of EDTA is kidney toxicity (5772,108095,108099,108102) for doses greater than 3 grams daily (15). In a clinical trial in patients with angina, intravenous disodium EDTA has resulted in an elevation of serum creatinine (108104). EDTA can cause nocturia, hyperuricemia, polyuria, dysuria, oliguria, proteinuria, glycosuria, hematuria. and distal tubule and glomeruli changes (15). EDTA can also cause acute renal tubular necrosis, renal insufficiency, and renal failure (5772).

(Read more about CHELATION THERAPY PRODUCTS)

General ...Orally, pantothenic acid is generally well tolerated. Topically and intramuscularly, dexpanthenol, a synthetic form of pantothenic acid, seems to be well tolerated.
Most Common Adverse Effects:
Topically: Burning, contact dermatitis, eczema, irritation, and itching related to dexpanthenol.

Cardiovascular ...There is one case of eosinophilic pleuropericardial effusion in a patient taking pantothenic acid 300 mg per day in combination with biotin 10 mg per day for 2 months (3914).

Dermatologic ...Topically, dexpanthenol has been associated with itching, burning, skin irritation, contact dermatitis, and eczema (67779,67781,67788,111258,111262). Three cases of allergic contact dermatitis have been reported (111260,111261).

Gastrointestinal ...Orally, pantothenic acid has been associated with diarrhea (67822,111258).

(Read more about PANTOTHENIC ACID)

General ...Orally, sweet orange juice or fruit seem to be well tolerated. Large amounts of sweet orange peel may be unsafe, especially for children. When inhaled, sweet orange essential oil seems to be generally well tolerated.

Gastrointestinal ...There have been reports of intestinal colic in children following ingestion of large amounts of sweet orange peel (11).

Neurologic/CNS ...There have been reports of convulsions in children following ingestion of large amounts of sweet orange peel (11).

(Read more about SWEET ORANGE)

General ...Orally or parenterally, transfer factor seems to be well tolerated (350,1445,1507,3062,3063,7562,7794,7797,7798,7799,78668,78669,78702,78714,78774,78796). Adverse effects may include fever (1507). Parenterally, transfer factor can cause nausea, fatigue, and tenderness, pain, and swelling at the injection site (3062,7562,7799,78809). Orally, severe acne has been reported (78820).
There is some concern that bovine-derived transfer factor that is 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). However, there have been no reports of BSE transfer to humans from contaminated transfer factor 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.

Dermatologic ...Orally, transfer factor may cause severe acne in some patients (78820).

Gastrointestinal ...Parenterally, nausea has been reported in a patient following treatment with transfer factor (78809)

Musculoskeletal ...Parenterally, transfer factor may cause tenderness, pain, and swelling at the injection site (3062,7562,7799,78809).

Neurologic/CNS ...Parenterally, fatigue has been reported for up to 4 hours in a patient using transfer factor (78789).

Other ...Orally or parenterally, transfer factor may cause fever (1507,78789,78809).
There is some concern that bovine-derived transfer factor that is 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). However, there have been no reports of BSE transfer to humans from contaminated transfer factor 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 TRANSFER FACTOR)