Aquella by Lifeplan Products Limited

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there has been interest in using topical apple cider vinegar for acne, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Athletic performance. It is unclear if oral apple cider vinegar is beneficial for improving endurance during exercise. Details: Preliminary clinical research in a small number of healthy male athletes shows that drinking apple cider vinegar 500 mL one-hour prior to an endurance cycling test does not improve endurance capacity, as measured by respiratory exchange rate, heart rate, or blood levels of ammonia, glucose, or lactate, when compared with a commercial sports drink (103225). It is unknown if apple cider vinegar would improve endurance when compared with a placebo control.
• Atopic dermatitis (eczema). Although there has been interest in using topical apple cider vinegar for eczema, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Cognitive function. Although there has been interest in using oral apple cider vinegar to improve cognitive function, there is insufficient reliable information about the clinical effects of apple cider vinegar for this use.
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral apple cider vinegar for COVID-19, there is insufficient reliable information about the clinical effects of apple cider vinegar for this use.
• Dandruff. Although there has been interest in using topical apple cider vinegar for dandruff, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Dental plaque. It is unclear if topical apple cider vinegar prevents the accumulation of dental plaque. Details: A small clinical study in children aged 3-6 years with cerebral palsy shows that applying apple cider vinegar 5% to their teeth daily for 6 months reduces the accumulation of dental plaque when compared with manual tooth brushing without dental paste (111228). However, the validity of these findings is limited by a lack of blinding and poor study methodology.
• Depression. Although there has been interest in using oral apple cider vinegar for depression, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Diabetes. It is unclear if oral apple cider vinegar is beneficial for improving glucose control in patients with type 2 diabetes; evidence is conflicting. Details: Two meta-analyses of mainly lower-quality clinical trials in a variety of populations (i.e., healthy, overweight, or obese individuals or those with type 2 diabetes) show that taking apple cider vinegar daily for up to 12 weeks reduces fasting blood glucose (FBG) levels by about 8-21 mg/dL, glycated hemoglobin (HbA1c) by 0.5%-0.9%, and total cholesterol by 6-7 mg/dL when compared with control (e.g., water, another beverage, no beverage, or restricted calorie diet). There was no effect on levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, insulin, or on measures of insulin resistance. However, in sub-group analyses limited to patients with type 2 diabetes, the effect of apple cider vinegar on FBG or HbA1c levels is conflicting (106284,112355). Of note, both meta-analyses include studies with heterogeneous populations, varied dosages, and different durations that limit the interpretation of these pooled results. Small clinical studies show varying results. One small open-label clinical study conducted in Iran in adults with type 2 diabetes shows that taking apple cider vinegar 30 mL daily for 8 weeks reduces HbA1c by about 1.4% but does not impact fasting blood glucose when compared with control (113626). Notably, baseline HbA1c was about 9% in the apple cider vinegar group versus about 8% in the control group. It is unclear if modifications to antidiabetes medications were allowed during study enrollment. Additionally, a very small clinical study shows that taking apple cider vinegar 20 grams with a meal increases postprandial insulin sensitivity and reduces postprandial flux in insulin levels in patients with insulin resistance, but not those with type 2 diabetes, when compared with placebo (17614). Additionally, a very small clinical study shows that taking apple cider vinegar 20 grams with a meal increases postprandial insulin sensitivity and reduces postprandial flux in insulin levels in patients with insulin resistance, but not those with type 2 diabetes, when compared with placebo (17614). It is unclear if the formulation of apple cider vinegar alters its effects. One small crossover study in healthy adults found a modestly greater reduction in postprandial glucose with the use of liquid apple cider vinegar (providing 1.25 grams acetic acid) when compared with apple cider vinegar whole tablets or crushed tablets (providing 1.5 grams acetic acid) or water alone (106285). Larger studies are needed to confirm this finding.
• Dyspepsia. Although there has been interest in using oral apple cider vinegar for dyspepsia, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Gastroparesis. It is unclear if oral apple cider vinegar is beneficial for gastroparesis. Details: A very small clinical study shows that taking apple cider vinegar 30 mL daily worsens the gastric emptying rate in patients with type 1 diabetes and gastroparesis when compared with drinking water (17609).
• Gingivitis. It is unclear if topical apple cider vinegar prevents the development of gingivitis. Details: A small clinical study in children aged 3-6 years with cerebral palsy shows that applying apple cider vinegar 5% to the teeth daily for 6 months reduces gingivitis scores when compared to baseline, with results comparable to manual tooth brushing without dental paste at the end of the study period (111228). However, the validity of these findings is limited by a lack of blinding and poor methodology.
• Herpes zoster (shingles). Although there has been interest in using topical apple cider vinegar for shingles, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Hyperlipidemia. It is unclear whether oral apple cider vinegar is beneficial for hyperlipidemia. Details: A small open-label clinical study conducted in Iran in adults with type 2 diabetes shows that taking apple cider vinegar 30 mL daily for 8 weeks reduces low-density lipoprotein (LDL) cholesterol and total cholesterol but does not impact high-density lipoprotein (HDL) cholesterol or triglycerides when compared with control (113626).
• Impaired glucose tolerance (prediabetes). Although there has been interest in using oral apple cider vinegar for prediabetes, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Insect bite. Although there has been interest in using topical apple cider vinegar for insect bites, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Intestinal parasite infection. Although there has been interest in using oral apple cider vinegar for intestinal parasite infections, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Kidney stones (nephrolithiasis). It is unclear if oral apple cider vinegar reduces the risk for kidney stones. Details: Some population research suggests that the consumption of fermented vinegar can reduce the risk for kidney stones (97311). However, there is currently no clinical evidence confirming this association, or any studies specifically evaluating the use of apple cider vinegar for this purpose.
• Leg cramps. Although there has been interest in using oral apple cider vinegar for leg cramps, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Obesity. It is unclear if oral apple cider vinegar is beneficial for obesity. Details: A small clinical study in overweight and obese adults shows that taking apple cider vinegar 15 mL twice daily for 12 weeks along with a calorie-restricted diet helps control appetite and modestly reduces body weight, body mass index (BMI), and hip girth when compared with a restricted calorie diet alone. Taking apple cider vinegar along with dieting also appears to increase high-density lipoprotein (HDL) cholesterol levels and decrease triglyceride levels, but not low-density lipoprotein (LDL) cholesterol levels, when compared to dieting alone (97310). Another small open-label clinical study conducted in Iran in adults with type 2 diabetes shows that taking apple cider vinegar 30 mL daily for 8 weeks reduces BMI and waist circumference but does not change waist-to-hip ratio when compared with control (113626). The validity of these results are limited by lack of statistical adjustment for multiple comparisons.
• Osteoarthritis. Although there has been interest in using oral apple cider vinegar for osteoarthritis, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Pharyngitis. Although there has been interest in using oral apple cider vinegar for pharyngitis, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Rhinosinusitis. Although there has been interest in using oral apple cider vinegar for rhinosinusitis, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Sunburn. Although there has been interest in using topical apple cider vinegar for sunburn, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Vaginal candidiasis. Although there has been interest in using topical apple cider vinegar for vaginal candidiasis, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Warts. Although there has been interest in using topical apple cider vinegar for warts, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition. More evidence is needed to rate apple cider vinegar for these uses.

(Read more about APPLE CIDER VINEGAR)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Dental plaque. It is unclear if oral Ascophyllum nodosum is beneficial in patients with dental plaque. Details: A small crossover study in adults with moderate to heavy calculus formation shows that taking a specific brand of Ascophyllum nodosum capsules (ProDen PlaqueOff, SDC Swedencar eAB) 500 mg daily for 6 months reduces the buildup of supragingival calculus by 52% when compared with placebo. The buildup of plaque was reduced by 19% in males, but was not reduced in females, when compared with placebo (94996).
• Gastroesophageal reflux disease (GERD). Although there has been interest in using oral Ascophyllum nodosum for GERD, there is insufficient reliable information about the clinical effects of Ascophyllum nodosum for this purpose.
• Gingivitis. It is unclear if oral Ascophyllum nodosum is beneficial in patients with dental plaque. Details: A small crossover study in adults with moderate to heavy calculus formation shows that taking a specific brand of Ascophyllum nodosum capsules (ProDen PlaqueOff, SDC Swedencar eAB) 500 mg daily for 6 months does not reduce gingivitis when compared with placebo (94996).
• Impaired glucose tolerance (prediabetes). Oral Ascophyllum nodosum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with prediabetes that are overweight or obese shows that taking a specific product (InSea2, InnoVactiv Inc.) containing 500 mg of Ascophyllum nodosum and Fucus vesiculosus extracts daily for 12 weeks reduces postprandial blood glucose but does not improve fasting blood glucose, glycated hemoglobin (HbA1c), body weight, lipids, or blood pressure when compared with placebo (110560).
• Inflammatory bowel disease (IBD). Although there has been interest in using oral Ascophyllum nodosum for IBD, there is insufficient reliable information about the clinical effects of Ascophyllum nodosum for this purpose.
• Iodine deficiency. It is unclear if oral Ascophyllum nodosum is beneficial in patients with iodine deficiency. Details: Ascophyllum nodosum contains iodine, and there is interest in its use for patients with iodine deficiency. A small clinical study in females with iodine insufficiency shows that taking a specific brand of Ascophyllum nodosum capsules (Napiers Hebridean Seagreens (NaHS), Seagreens Ltd) 500 mg daily for 14 days increases urinary iodine excretion by almost three-fold and increases thyroid stimulating hormone levels by 36% when compared with baseline (94997). The validity of these findings is limited by the lack of a control group.
• Metabolic syndrome. Oral Ascophyllum nodosum 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 Ascophyllum nodosum and Fucus vesiculosus in a 95:5 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 Ascophyllum nodosum, Fucus vesiculosus, or the combination. Further, the validity of these findings is limited by a lack of control group.
• Obesity. Oral Ascophyllum nodosum has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with prediabetes that are overweight or obese shows that taking a specific product (InSea2, InnoVactiv Inc.) containing 500 mg of Ascophyllum nodosum and Fucus vesiculosus 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).
• Peptic ulcers. Although there has been interest in using oral Ascophyllum nodosum for peptic ulcers, there is insufficient reliable information about the clinical effects of Ascophyllum nodosum for this purpose. More evidence is needed to rate Ascophyllum nodosum for these uses.

(Read more about ASCOPHYLLUM NODOSUM)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Benign prostatic hyperplasia (BPH). Oral boldo has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with BPH, some of whom were already receiving conventional treatment such as alpha-1 blockers, shows that taking a specific product containing water-soluble extracts of boldo, goldenrod, chanca piedra, fireweed, and spiny restharrow (Fluxonorm, Omega Pharma) orally for 30 days improves lower urinary tract symptom scores by about 50% when compared with baseline. Maximum urinary flow rate and quality of life were also improved when compared with baseline (106432). The validity of these findings is limited by the lack of a comparator group.
• Gallbladder disease. Although there has been interest in using oral boldo for gallbladder disease, there is insufficient reliable information about the clinical effects of boldo for this purpose.
• Gonorrhea. Although there has been interest in using oral boldo for gonorrhea, there is insufficient reliable information about the clinical effects of boldo for this purpose.
• Kidney stones (nephrolithiasis). Oral boldo has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children 6-18 years of age with upper ureteral tract kidney stones shows that taking a specific combination product containing boldo 200 mg, uva ursi 300 mg and Herniaria hirsuta 40 mg (Renalit-combi, Bio-Stilogit Pharmaceuticals) orally for 12 days each month for 3 months after undergoing lithotripsy, in addition to standard care, reduces presence of residual stone fragments by 58% when compared with standard care alone (109936).
• Joint pain. Although there has been interest in using oral boldo for joint pain, there is insufficient reliable information about the clinical effects of boldo for this purpose. More evidence is needed to rate boldo for these uses.

(Read more about BOLDO)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there is interest in using topical burdock for acne, there is insufficient reliable information about the clinical effects of burdock for this purpose.
• Aging skin. It is unclear if topical burdock is beneficial for reducing wrinkles. Details: A very small study in females aged 39-65 years shows that applying an emulsion containing burdock fruit extract 1.2% to the face twice daily for 4 weeks slightly reduces skin wrinkles around the eyes when compared with placebo (37420).
• Atopic dermatitis (eczema). Although there is interest in using topical burdock for eczema, there is insufficient reliable information about the clinical effects of burdock for this condition.
• Breast cancer. Oral burdock root has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Population research in breast cancer patients has found that using a specific product containing burdock root, sheep sorrel, slippery elm bark, and Indian rhubarb (Essiac, Resperin Canada Limited) is not associated with improved quality of life when compared with no intervention (37419).
• Common cold. Although there is interest in using oral burdock for symptoms of the common cold, there is insufficient reliable information about the clinical effects of burdock for this condition.
• Diabetes. Although there is interest in using oral burdock for diabetes, there is insufficient reliable information about the clinical effects of burdock for this condition.
• Diverticulitis. It is unclear if oral burdock is beneficial in patients with diverticulitis. Details: A small open-label clinical study in patients with colonic diverticulitis shows that taking burdock tea (Ajikan, Co., Ltd.) providing 1.5 grams three times daily for a median of 26 months is associated with an acute diverticulitis recurrence rate of 11%, compared with 32% of those not taking burdock tea. Furthermore, the recurrence-free duration was increased by about 14 months. However, taking burdock tea for a median of 16 months does not prevent colonic diverticular bleeding recurrence (102696).
• Dry skin. Although there is interest in using topical burdock for dry skin, there is insufficient reliable information about the clinical effects of burdock for this purpose.
• Gout. Although there is interest in using oral burdock for gout, there is insufficient reliable information about the clinical effects of burdock for this condition.
• Hepatitis. Although there is interest in using oral burdock for hepatitis, there is insufficient reliable information about the clinical effects of burdock for this condition.
• Metabolic syndrome. It is unclear if oral burdock is beneficial in patients with metabolic syndrome. Details: A very small clinical study in patients with metabolic syndrome shows that drinking burdock extract 100 mL three times daily after meals for 16 weeks does not reduce body weight, abdominal fat, blood pressure, lipid levels, or glucose when compared with baseline or control (105667).
• Obesity. Although there is interest in using oral burdock for obesity, there is insufficient reliable information about the clinical effects of burdock for this condition.
• Urinary tract infections (UTIs). Although there is interest in using oral burdock for UTI, there is insufficient reliable information about the clinical effects of burdock for this condition.
• Vaginitis. Topical burdock has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Observational research in adults and children with vaginitis has found that applying a specific solution containing burdock, chamomile, and aloe (Zelesse, ITF Research Pharma S.L.U., Alcobendas) to the vaginal area once or twice daily for 5-20 days is associated with moderate improvements in symptoms such as pruritus, erythema, and discharge when compared with baseline (102695,102697). The validity of this finding is limited by its observational nature and the lack of a control group. More evidence is needed to rate burdock for these uses.

(Read more about BURDOCK)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Constipation. Although there has been interest in using oral dandelion for constipation, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Dyspepsia. Although there has been interest in using oral dandelion for dyspepsia, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Flatulence. Although there has been interest in using oral dandelion for flatulence, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Heart failure. Although there has been interest in using oral dandelion for its diuretic effects in patients with heart failure, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Joint pain. Although there has been interest in using oral or topical dandelion for joint pain, there is insufficient reliable information about the clinical effects of dandelion for this purpose.
• Postoperative pain. It is unclear if topical dandelion is beneficial in patients with pain after jaw surgery. Details: A small clinical study in patients undergoing maxillofacial surgery shows that topical application of dandelion combined with borneol one time on the day of surgery and twice daily on the first and second days after surgery for 30 minutes does not reduce maxillofacial pain when compared with cold compresses or either ingredient alone (112484). The validity of this finding is limited by concurrent use of opioid analgesic and nonsteroidal anti-inflammatory medications.
• Postoperative swelling. It is unclear if topical dandelion is beneficial in patients with swelling after jaw surgery. Details: A small clinical study in patients who underwent maxillofacial surgery shows that topical application of dandelion combined with borneol one time on the day of surgery and twice daily on the first and second days after surgery for 30 minutes modestly reduces facial swelling and improves mouth opening abilities when compared with cold compresses or borneol alone (112484). It is unclear whether this effect is due to dandelion, borneol, or the combination.
• Tonsillitis. It is unclear if oral dandelion is beneficial in patients with tonsillitis. Details: One small clinical study in patients with acute purulent tonsillitis shows that eating soup containing dandelion (pugongying soup) daily for 3 days along with benzylpenicillin sodium 640,000 units daily improves recovery when compared with placebo plus benzylpenicillin sodium. Recovery rates were 36% with the dandelion-containing soup compared to 10% with placebo (18292).
• Urinary tract infections (UTIs). Oral dandelion has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in females with recurrent UTIs shows that taking a specific combination of dandelion root and uva ursi leaf extracts three times daily for 1 month reduces the risk of UTI recurrence when compared with placebo at 12-month's follow-up. For every 5 patients treated with this combination over placebo, one additional UTI was prevented (1932). In this combination, uva ursi is used for its antibacterial properties and dandelion is used to increase urination. However, this combination is not recommended for extended use because uva ursi may be unsafe when used long-term. Another small clinical study in premenopausal females with acute, uncomplicated lower UTIs shows that taking a combination product containing dandelion extract 50 mg, D-mannose, prebiotics, arabinogalactan, and astragalus root extract twice daily for five days, along with phenazopyridine and alkylating agents as conventional therapy, improves UTI symptoms and bacteriuria when compared with placebo plus conventional therapy (111757). It is unclear if these effects are due to dandelion, other ingredients, or the combination. More evidence is needed to rate dandelion for these uses.

(Read more about DANDELION)

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)

POSSIBLY INEFFECTIVE

• Abortion. Despite traditional use for the induction of second trimester abortion, most research shows that intravaginal laminaria does not significantly reduce time to delivery or improve abortion rates, and it may actually worsen some outcomes when compared with standard of care. Details: One clinical study shows that intravaginal administration of laminaria along with misoprostol does not improve second trimester abortion rates at 24 and 48 hours after treatment initiation when compared with using only misoprostol. Also, using laminaria along with misoprostol does not shorten delivery time when compared with misoprostol alone (95688). Another small clinical study shows that adding intravaginal laminaria to misoprostol therapy significantly increases induction time and the need for opioid analgesics when compared with misoprostol alone (109576). Also, a small clinical study in patients undergoing second trimester abortions shows that intravaginal laminaria increases pain with cervical ripening and induction-to-delivery time when compared with mifepristone (109577). A retrospective study in 126 patients undergoing second trimester abortions has found that intravaginal administration of laminaria (Dilateria, Cooper Surgical) one day before using misoprostol might actually prolong delivery time by about 6 hours and does not improve abortion rates at 24 hours after induction when compared with misoprostol alone (105806). Some research shows that intravaginal administration of laminaria (Dilateria, Milex Products Inc.) one day before using prostaglandin E2 (PGE2) suppositories to induce second trimester abortions shortens the delivery time by about 3 hours when compared with PGE2 suppositories alone; however, the incidence of febrile episodes is about 2.3-fold higher for patients treated with laminaria (94045). Also, one small clinical study shows that intravaginal administration of laminaria the night before a scheduled abortion reduces procedure time by around 4 minutes, increases cervical dilation at the time of abortion, and reduces the need for additional dilation when compared with misoprostol treatment on the day of abortion. However, more patients preferred misoprostol over laminaria (109575). Laminaria has also been compared with a mechanical cervical dilation device, called Dilapan-S. A small clinical study in patients undergoing second trimester surgical abortion shows that intravaginal administration of laminaria for cervical preparation has no effect on pain scores or analgesic use following dilator placement or dilation and evacuation (D&E) when compared with Dilapan-S. The validity of these findings may be limited by the single-blinded nature of the study, as well as significant baseline differences between the treatment groups with respect to vaginal parity (105805).
• Parturition. Intravaginal administration of laminaria does not seem to be beneficial for cervical ripening. Details: While some research suggests that intravaginal laminaria might reduce the duration of induction, results are conflicting. Additionally, studies suggest that intravaginal laminaria does not seem to reduce the incidence of birth by caesarean section (8945,95689,102765). Also, a small observational study has found that intravaginal laminaria is associated with a greater risk of endometritis and fetal infectious complications when compared with a control group not receiving laminaria (8945).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acute radiation syndrome. Although there has been interest in using oral laminaria for acute radiation syndrome, there is insufficient reliable information about the clinical effects of laminaria for this purpose.
• Cancer. Although there has been interest in using oral laminaria for cancer prevention, there is insufficient reliable information about the clinical effects of laminaria for this purpose.
• Hypertension. Although there has been interest in using oral laminaria for hypertension, there is insufficient reliable information about the clinical effects of laminaria for this purpose.
• Obesity. It is unclear if oral laminaria is beneficial in patients with obesity. Details: A small clinical study in overweight Japanese adults shows that taking iodine-reduced laminaria powder 2 grams, providing 1 gram of alginate, three times daily for 8 weeks reduces body fat percentage in males, but not females, when compared with placebo. Laminaria does not affect body weight or body mass index when compared with placebo (109572).
• Radiation exposure. Although there has been interest in using oral laminaria to minimize environmental radiation exposure, there is insufficient reliable information about the clinical effects of laminaria for this purpose. More evidence is needed to rate laminaria for these uses.

(Read more about LAMINARIA)

LIKELY SAFE ...when used orally and appropriately in food amounts.

POSSIBLY SAFE ...when used orally and appropriately, short-term for medicinal purposes. Apple cider vinegar has been safely used in short-term studies for up to 12 weeks (17609,17614,97310).

POSSIBLY UNSAFE ...when used topically. Topical application of apple cider vinegar has been reported to cause chemical burns in at least three patients. Mild skin irritation is common (91662,93074,101172). ...when used orally in large amounts, long-term. A case of hypokalemia, hyperreninemia, and osteoporosis has been reported for a patient who consumed apple cider vinegar 250 mL daily for 6 years (31730).

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

(Read more about APPLE CIDER VINEGAR)

POSSIBLY SAFE ...when used orally, short-term. Ascophyllum nodosum dried powder has been used with apparent safety at a dose of up to 500 mg daily for up to 6 months (94996,94997,103900). However, marine products such as Ascophyllum nodosum are known to accumulate heavy metals such as arsenic (94997,94999). Some supplement products are prospectively analyzed to confirm a lack of contaminants and that heavy metal levels are below threshold (94997).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using amounts greater than those found in food.

(Read more about ASCOPHYLLUM NODOSUM)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Boldo has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912).

POSSIBLY UNSAFE ...when used orally in medicinal amounts. The volatile oil (2.5% in the leaf) contains the liver toxin ascaridole (4). Boldo has also been linked to a documented case of liver damage (13178). If boldo preparations are taken for medicinal purposes, only ascaridole-free preparations should be used. There is insufficient reliable information available about the safety of boldo when used topically.

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in medicinal amounts. In animals, boldo and the constituent boldine have abortive and teratogenic effects (100302). Also, the ascaridole constituent of boldo is a liver toxin (4).

(Read more about BOLDO)

LIKELY SAFE ...when used in amounts commonly found in foods (12659,12660). Burdock root is commonly eaten as a vegetable (37422,92153,92154)

POSSIBLY SAFE ...when used topically, short-term. An emulsion containing burdock fruit extract 1.2% has been safely applied to the face twice daily for 4 weeks (37420). There is insufficient reliable information available about the safety of burdock when used orally in supplemental doses.

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

(Read more about BURDOCK)

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

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (12). There is insufficient reliable information available about the safety of dandelion when used topically.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using amounts greater than those in foods.

(Read more about DANDELION)

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 in amounts found in foods. Laminaria has Generally Recognized as Safe (GRAS) status in the US (94048).

POSSIBLY SAFE ...when iodine-reduced laminaria supplements are used, short-term. Iodine-reduced laminaria powder has been safely used at doses up to 6 grams daily for up to 8 weeks (109572).

POSSIBLY UNSAFE ...when used orally in medicinal amounts. The average laminaria-based supplement might contain as much as 1000 mcg of iodine. Ingesting more than 1100 mcg iodine daily (the tolerable upper intake level) can cause hypothyroidism, hyperthyroidism, or exacerbate existing hyperthyroidism (9556,94046). In addition, some laminaria supplements may contain arsenic (645,10275,15588). There is insufficient reliable information available about the safety of laminaria for its other uses.

PREGNANCY: POSSIBLY UNSAFE
when used intravaginally for cervical ripening; there is an increased risk of parental and neonatal infection (8945).

PREGNANCY: LIKELY UNSAFE
when used intravaginally to induce labor; use has been associated with endometriosis, neonatal sepsis, fetal hypoxia, and intrauterine death (6).

PREGNANCY: UNSAFE
when used orally due to potential hormonal effects (19); avoid using.

LACTATION: LIKELY UNSAFE
when used orally because of potential toxicity (19).

(Read more about LAMINARIA)

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking apple cider vinegar with antidiabetes drugs might increase the risk of hypoglycemia.  Details Apple cider vinegar might reduce fasting and postprandial blood glucose levels and decrease gastric emptying in people with diabetes (17609,17614,106285,106287). However, not all research agrees (106284). Theoretically, it might have additive effects on glucose levels when used with antidiabetes drugs.

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of apple cider vinegar with digoxin might increase the risk of cardiac toxicity.  Details A case of hypokalemia related to chronic use of apple cider vinegar has been reported (5911). Theoretically, overuse of apple cider vinegar could decrease potassium levels, increasing the risk of toxicity with digoxin.

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of apple cider vinegar with diuretic drugs might increase the risk of hypokalemia.  Details A case of hypokalemia related to chronic use of apple cider vinegar has been reported (5911). There is some concern that people taking apple cider vinegar along with potassium depleting diuretics might have an increased risk for hypokalemia.

INSULIN Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of apple cider vinegar with insulin might increase the risk of hypokalemia.  Details A case of hypokalemia related to chronic use of apple cider vinegar has been reported (5911). Theoretically, overuse of apple cider vinegar concomitantly with insulin might increase the risk of hypokalemia (5911).

(Read more about APPLE CIDER VINEGAR)

AMIODARONE (Cordarone) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, combining Ascophyllum nodosum with amiodarone might cause excessively high iodine levels.  Details Ascophyllum nodosum contains iodine (94997,95000,95102), although the bioavailability of iodine from Ascophyllum nodosum is lower than that of potassium iodide (94997). 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.

ANTITHYROID DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Due to its iodine content, Ascophyllum nodosum might alter the effects of antithyroid drugs.  Details Ascophyllum nodosum contains iodine (94997,95000,95102), although the bioavailability of iodine from Ascophyllum nodosum is lower than that of potassium iodide (94997). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking Ascophyllum nodosum while using antithyroid drugs could alter the effects of the antithyroid drugs (17574).

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Due to its iodine content, Ascophyllum nodosum might alter the effects of thyroid hormone.  Details Ascophyllum nodosum contains iodine (94997,95000,95102), although the bioavailability of iodine from Ascophyllum nodosum is lower than that of potassium iodide (94997). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking Ascophyllum nodosum while using thyroid hormone could alter the effects of thyroid hormone (17574).

(Read more about ASCOPHYLLUM NODOSUM)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking boldo with anticoagulant/antiplatelet drugs might increase the risk of bleeding.  Details Animal and in vitro research shows that boldine, a constituent of boldo, has antiplatelet activity (5191,36789). In one case report, an adult taking a combination of boldo and fenugreek with warfarin experienced an increase in international normalized ratio (INR); however, it is unclear if this effect was due to boldo, fenugreek, the combination, or another factor (5191).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking boldo with hepatotoxic drugs might increase the risk of hepatic injury and disease.  Details Boldo leaf contains ascaridole, a known liver toxin. Many cases of hepatotoxicity, including elevated liver transaminase levels and jaundice, have been reported in patients taking boldo (13178,100304,106431).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, taking boldo with lithium might increase the levels and clinical effects of lithium.  Details Boldo is believed to have diuretic effects (4). Theoretically, these diuretic effects might reduce the excretion of lithium. The dose of lithium might need to be decreased.

TACROLIMUS (Prograf) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Taking boldo with tacrolimus may decrease the levels and clinical effects of tacrolimus, potentially increasing the risk of transplant rejection.  Details In one case report, a patient with a long-term history of stable tacrolimus levels developed subtherapeutic levels after taking boldo 300 mg twice daily orally for several weeks. Tacrolimus levels returned to normal after discontinuing boldo. However, the mechanism of this interaction is unclear (92601).

(Read more about BOLDO)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking burdock with anticoagulant or antiplatelet drugs might increase the risk of bleeding.  Details In vitro research shows that lignans from burdock reduce rabbit platelet aggregation by inhibiting platelet activating factor (12619). This interaction has not been reported in humans.

(Read more about BURDOCK)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking dandelion root along with anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding.  Details In vitro research suggests that dandelion root inhibits platelet aggregation (18291).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase the risk for hypoglycemia when used with antidiabetes drugs.  Details Laboratory research suggests that dandelion extract may have moderate alpha-glucosidase inhibitor activity and might also increase insulin secretion (13474,90926). Also, in a case report, a 58-year-old woman with type 2 diabetes who was being treated with insulin developed hypoglycemia 2 weeks after beginning to eat salads containing dandelion (46960).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase levels of drugs metabolized by CYP1A2.  Details Laboratory research suggests that dandelion might inhibit CYP1A2 (12734). So far, this interaction has not been reported in humans. However, until more is known, watch for an increase in the levels of drugs metabolized by CYP1A2 in patients taking dandelion.

GLUCURONIDATED DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase the clearance of drugs that are UDP-glucuronosyltransferase substrates.  Details There is some preliminary evidence that dandelion might induce UDP-glucuronosyltransferase, a phase II enzyme (12734).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, through diuretic effects, dandelion might reduce excretion and increase levels of lithium.  Details Animal research suggests that dandelion has diuretic properties (13475). As diuretics can increase serum lithium levels, the dose of lithium might need to be decreased when taken with dandelion.

POTASSIUM-SPARING DIURETICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might increase the risk of hyperkalemia when taken with potassium-sparing diuretics.  Details Dandelion contains significant amounts of potassium (13465).

QUINOLONE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dandelion might lower fluoroquinolone levels.  Details Animal research shows that dandelion reduces absorption of ciprofloxacin and can lower levels by 73% (13477). However, this effect has not been reported in humans.

(Read more about DANDELION)

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)

ACE INHIBITORS (ACEIs) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, laminaria might increase the risk of hyperkalemia when taken with ACEIs.  Details Laminaria contains potassium (19).

AMIODARONE (Cordarone) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, combining laminaria with amiodarone might cause excessively high iodine levels.  Details Amiodarone contains 37.3% iodine and can increase iodine levels. Concomitant use with laminaria supplements, some of which may contain as much as 1000 mcg iodine, might increase the risk of adverse effects from iodine, including altered thyroid function (9556,94046).

ANTITHYROID DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Due to its iodine content, laminaria might alter the effects of antithyroid drugs.  Details Some laminaria supplements contain up to 1000 mcg of iodine (9556,94046). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking laminaria could theoretically alter the effects of antithyroid drugs.

DIGOXIN (Lanoxin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, laminaria might increase the risk of hyperkalemia, which could increase the effects and adverse effects of digoxin.  Details Laminaria contains potassium (19).

POTASSIUM-SPARING DIURETICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, laminaria might increase the risk of hyperkalemia when taken with potassium-sparing diuretics.  Details Laminaria contains potassium (19).

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Due to its iodine content, laminaria might alter the effects of thyroid hormone.  Details Some laminaria supplements contain up to 1000 mcg of iodine (9556,94046). Iodine in high doses has been reported to cause both hyperthyroidism and hypothyroidism, depending on the individual's past medical history. Taking laminaria could theoretically alter the effects of thyroid hormone.

(Read more about LAMINARIA)

General ...In food amounts, apple cider vinegar is well tolerated. It seems to be well tolerated when used orally, short-term for medicinal purposes. However, in larger amounts, long-term use may be unsafe.
Topically, apple cider vinegar may be unsafe.
Serious Adverse Effects (Rare):
Orally: Hypokalemia, hyperreninemia, and osteoporosis have been reported with long-term use.
Topically: Chemical burns, skin irritation.

Dermatologic ...Topically, apple cider vinegar may cause chemical burns. There is one published report of an individual who developed a chemical burn caused by a single topical application of apple cider vinegar containing 5% acetic acid to the skin (91662). Another case of chemical burn has been reported for a 14-year-old patient who applied apple cider vinegar to the skin for 3 days to remove a nevi. Symptoms included erythema, irritation, and non-inflammatory skin erosion. Symptoms were treated by applying mupirocin 2% ointment twice a day for several weeks and using sunscreen on the erosion and surrounding skin (93074). In one clinical trial, use of 0.5% apple cider vinegar soaks commonly caused skin irritation. One patient in this study experienced a nonpruritic papular rash, while another patient experienced severe pruritis with burning and erosion (101172). In another report, a female had an apple cider vinegar tablet lodged in the throat for 30 minutes, resulting in tenderness and pain in the larynx and difficulty swallowing for 6 months following the incident. This was thought to be due to the acid content of the tablet (13183).

Renal ...There is one published report of an individual who developed hypokalemia, elevated renin levels, high positive urinary anion gap, and osteoporosis after ingesting apple cider vinegar 250 mL per day for 6 years. The osteoporosis was attributed to buffering of the acute acid load by bone, and the other effects were attributed to significant bicarbonate excretion (31730).

(Read more about APPLE CIDER VINEGAR)

General ...Orally, Ascophyllum nodosum seems to be generally well-tolerated.

Endocrine ...Orally, taking Ascophyllum nodosum powder 500 mg daily for 14 days has been reported to cause elevated levels of thyroid stimulating hormone (TSH) in 2 of 22 women in a clinical trial. The powder contained 356 mcg iodine per 500 mg. Levels of free thyroxine (T4) were unaffected (94997).

Gastrointestinal ...Orally, Ascophyllum nodosum has been reported to cause stomach discomfort in one clinical trial (94996).

(Read more about ASCOPHYLLUM NODOSUM)

General ...Orally, boldo is generally well tolerated when used in amounts commonly found in foods. However, when used in medicinal amounts, boldo can cause significant adverse effects such as hepatotoxicity. There is currently a limited amount of information on the adverse effects of topical boldo; however, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Abdominal pain, nausea, vomiting.
Topically: Dermatitis.
Severe Adverse Effects (Rare):
Orally: Hepatotoxicity, jaundice.

Cardiovascular ...In one report, a 39-year-old obese female developed palpitations and syncope after taking a weight loss supplement containing a combination of boldo, dandelion, and bladderwrack for 3 weeks. The patient was found to have prolonged QT-interval on ECG and frequent episodes of sustained polymorphic ventricular tachycardia (14321). It is not clear whether boldo, 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.

Dermatologic ...Topically, boldo can be irritating when applied to the skin (4). In one case report, a healthy 64-year-old patient experienced allergic contact dermatitis in an airborne pattern on the face, arms, and dorsum of both hands following airborne exposure to boldo. After exposure to boldo was avoided, the dermatitis resolved (106433).

Gastrointestinal ...In one case report, a manufacturer of an herbal laxative reformulated their product to contain boldo. Within 5 months of switching to this reformulated product, an 82-year-old male developed abdominal discomfort with gastrointestinal upset including heartburn (13178). In another case, a 72-year-old female reported nausea, vomiting, and anorexia, which were thought to be associated with hepatotoxic effects of a boldo infusion (100304).

Hepatic ...Orally, boldo is thought to potentially cause hepatotoxicity. The volatile oil from the boldo leaf contains the liver toxin, ascaridole. In one case report, a manufacturer of an herbal laxative reformulated their product to contain boldo. Within 5 months of switching to this reformulated product, an 82-year-old male with mild hepatic steatosis and very small gallbladder stones developed elevated liver transaminase levels. Levels normalized following discontinuation of the herbal product (13178). Several other cases of hepatotoxicity have been reported in elderly patients who received infusions of boldo leaves. These patients presented with elevated liver transaminase and bilirubin levels, sometimes up to 200 times the upper limit of normal, as well as nausea, vomiting, anorexia, asthenia, and jaundice. Lab tests and symptoms normalized a few days after stopping boldo (100304,106431).

Immunologic ...Boldo intake has been linked to one case of IgE-mediated anaphylactic allergic reaction (13185).

(Read more about BOLDO)

General ...Orally, burdock is well tolerated when consumed as a food. Although a thorough evaluation of safety outcomes is lacking, there has been long-standing historical use of burdock with few noted adverse effects.
Serious Adverse Effects (Rare):
All ROAs: Allergic reactions, including contact dermatitis and anaphylaxis.

Dermatologic ...Contact dermatitis has been reported secondary to burdock, especially after prolonged use of the root oil (37422). There are cases of allergic dermatitis secondary to using burdock plasters. Two males and a 14 year-old female developed erythematous and vesicular, pruritic, and exudative reactions in areas corresponding to the application of burdock root plasters (12667). Reactions occurred up to 7 days after initial use. Patch testing was positive for burdock sensitivity in all three patients and was nonreactive in matched controls.

Hematologic ...In one case report, a 38-year-old female developed immune-mediated thrombocytopenia after consuming a "cleansing" tea containing unknown amounts of burdock and yellow dock. The patient presented with bruising, mild weakness, and fatigue, which started 2-3 days after consuming the tea, and was found to have a platelet count of 5,000 per mcL. Symptoms resolved after platelet transfusion and treatment with oral dexamethasone (108971). It is unclear if these effects were caused by burdock, yellow dock, the combination, or other contributing factors.

Hepatic ...A case of idiosyncratic drug-induced liver disease (DILI) is reported in a 36-year-old female who presented with abdominal pain after 1 month of taking an herbal liver detox tea containing burdock and other ingredients. Remarkable laboratory values included elevated liver enzymes, alkaline phosphatase, and total bilirubin. The patient received a loading dose of N-acetylcysteine and was hospitalized for 12 days (112178). However, it is unclear if the adverse effect was due to burdock, other ingredients, or the combination.

Immunologic ...There is one case of anaphylactic shock secondary to eating boiled burdock. One hour after eating boiled burdock the patient presented with redness over the entire body and dyspnea. He was found to have low blood pressure and was treated with subcutaneous epinephrine 1 mg and intravenous lactated ringer's solution containing hydrocortisone 100 mg and dexamethasone 8 mg. The cause of anaphylactic shock was attributed to allergenicity to burdock based on positive skin prick test results. Previously, the patient had experienced urticaria after eating boiled burdock (12660).

Neurologic/CNS ...Anticholinergic reactions including dry mouth, dizziness, blurred vision, weakness, dilated pupils, inability to urinate, and bradycardia have been reported following the consumption of burdock products (12662,37421,37431,37434,37435). However, these anticholinergic reactions are believed result from contamination of burdock with belladonna alkaloids. Burdock itself does not contain atropine or other constituents that would be responsible for these reactions.

(Read more about BURDOCK)

General ...Orally, dandelion seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, heartburn, and stomach discomfort.
Topically: Dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.

Cardiovascular ...In one report, a 39-year-old obese woman developed palpitations and syncope after taking a weight loss supplement containing a combination of dandelion, bladderwrack, and boldo for 3 weeks. The patient was found to have prolonged QT-interval on ECG and frequent episodes of sustained polymorphic ventricular tachycardia (14321). It is not clear whether dandelion, 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.

Dermatologic ...Topically, dandelion can cause contact dermatitis and erythema multiforme in sensitive individuals. Dandelion can cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family (13478,13481,42893,46945,46977). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Endocrine ...In one report, a 56-year-old man with renal impairment developed hyperoxalaemia and peripheral gangrene after ingesting large amounts of dandelion tea (10 to 15 cups daily for 6 months). The adverse effect was attributed to the high oxalate content of dandelion tea (258 mcmol/L) and reduced renal oxalate clearance caused by renal impairment (90639). In another report, a 58-year-old woman with type 2 diabetes who was being treated with insulin developed hypoglycemic symptoms 2 weeks after beginning to eat salads containing dandelion (46960). The hypoglycemic effect was attributed to the potential alpha-glucosidase inhibitory activity of dandelion.

Gastrointestinal ...Gastrointestinal symptoms, including stomach discomfort, diarrhea, and heartburn, have been reported following oral use of dandelion (19146,36931). A case of intestinal blockage has been reported for a patient who ingested a large amount of dandelion greens three weeks after undergoing a stomach operation (46981). Also, a case of hemorrhagic cystitis has been reported for a 33-year-old woman who took a specific herbal product (Slim-Kombu, Balestra and Mech, Vicenza, Italy) containing 20 herbal extracts, including dandelion extract. Symptoms resolved after the patient discontinued using the product, and symptoms resumed when the patient began taking the supplement again four months later. While various ingredients in the supplement may have contributed to the symptoms, it is possible that dandelion extract may have contributed to the effect due to its diuretic, laxative, cholagogue, and antirheumatic properties (46959).

Other ...Orally, products containing dandelion pollen can cause allergic reactions, including anaphylaxis (13479,13480). Also, rhinoconjunctivitis and asthma have been reported after handling products such as bird feed containing dandelion and other herbs, with reported positive skin tests for dandelion hypersensitivity (46948). Dandelion pollen may cause pollinosis, such as allergic rhinitis and conjunctivitis (18065,46951,46964,46966,46972).

(Read more about DANDELION)

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-reduced laminaria seems to be well tolerated, while other laminaria formulations may contain excess amounts of iodine, as well as arsenic.
Most Common Adverse Effects:
Intravaginally: Cervical bleeding and pelvic cramps.
Serious Adverse Effects (Rare):
Orally: Arsenic poisoning.
Intravaginally: Rupture of cervical wall, fetal hypoxia, and fetal death. Anaphylaxis in sensitive individuals.

Dermatologic ...Orally, laminaria has been linked to a report of induced or exacerbated acne (9555).

Endocrine ...Orally, laminaria can affect levels of certain thyroid hormones, and might cause hypothyroidism or hyperthyroidism, or exacerbate existing hyperthyroidism (9556,94046).

Genitourinary ...Intravaginally, laminaria used for cervical ripening can cause pelvic cramps and cervical bleeding (8945). Uterine contractions associated with laminaria use have been implicated in fetal hypoxia and subsequent intrauterine death (6). Use of endocervical laminaria tents has been associated with possible rupture of the cervical wall and subsequent neonatal and parental infection (6,8945).

Immunologic ...There are case reports of anaphylactic reactions to laminaria when used intravaginally as a cervical dilator. In at least one case, ventilation was required (102766).

Other ...Laminaria concentrates arsenic from the ocean. In one case, use of an oral laminaria supplement for several months resulted in symptoms of arsenic poisoning including headache, weakness, fatigue, worsening memory loss, rash, nail damage, diarrhea, and vomiting. Urinary arsenic levels were elevated (15588). The concentration of arsenic in laminaria may vary between different batches, and also depends upon the part of the world where it was harvested (645,10275,15588). The concentration of arsenic has been reported to be higher in preparations from Australia than from Great Britain (645,10275).

(Read more about LAMINARIA)