SlimStyles PGX Ultra Matrix Plus Soothe Digest by Natural Factors

There is insufficient reliable information available about the effectiveness of algin.

(Read more about ALGIN)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Asthma. Oral anise has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with allergic asthma shows that drinking one cup of tea prepared with multiple ingredients, including anise, twice daily for 6 months reduces sleep discomfort, cough frequency, and cough intensity when compared with placebo (19056). It is unclear if these findings are due to anise, other ingredients, or the combination.
• Constipation. Oral anise has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small crossover trial in patients with constipation shows that taking an herbal tea containing a combination of anise, fennel, elderberry, and senna daily for 5 days can decrease colon transit time, increase the number of daily evacuations, and improve the perception of bowel function when compared with placebo (49494). It is unclear if these findings are due to anise, other ingredients, or the combination.
• Depression. It is unclear if oral anise oil is beneficial in patients with depression. Details: A small clinical study in adults with mild to moderate depression and irritable bowel syndrome (IBS) shows that taking enteric-coated anise oil 200 mg three times daily for 4 weeks improves symptoms of depression by an additional 28% when compared with placebo and an additional 32% when compared with peppermint (94947).
• Diabetes. It is unclear if oral anise seed powder is beneficial in patients with diabetes. Details: A small clinical study in adults with type 2 diabetes shows that taking anise seed powder 5 grams daily for 60 days decreases fasting blood glucose levels by 36%, total cholesterol levels by 7.5%, and triglyceride levels by 15% when compared to baseline. Fasting blood glucose significantly increased in the control group, and total cholesterol and triglyceride levels were relatively unchanged (94953).
• Dysmenorrhea. Although there has been interest in using oral anise for dysmenorrhea, there is insufficient reliable information about the clinical effects of anise for this purpose.
• Dyspepsia. It is unclear if oral anise powder is beneficial in patients with dyspepsia. Details: A small clinical study in adults with postprandial distress syndrome shows that taking anise powder 3 grams three times daily for 4 weeks improves quality of life and symptoms of functional dyspepsia when compared with placebo. Of the evaluated symptoms, improvement was seen in all categories when compared to placebo except for nausea and vomiting, which were present in less than 5% of patients at baseline (94944,94945).
• Irritable bowel syndrome (IBS). It is unclear if oral anise oil is beneficial inpatients with IBS. Details: A small clinical study in adults with IBS shows that taking enteric-coated anise oil 200 mg three times daily for 4 weeks eliminates IBS symptoms in 75% of patients, compared with 53% of patients taking peppermint oil and 35% taking placebo. The greatest symptom improvement occurred with abdominal pain, bloating, and reflux, and was maintained for an additional 2 weeks after treatment completion (94946).
• Lactation. It is unclear if oral anise tea is beneficial for increasing human milk production. Details: A moderate-sized clinical study in post-partum adults shows that drinking a tea containing anise 2 grams and black tea 1 gram 3 times daily with meals for 7 days increases the volume of pumped human milk on day 7 by an average of 98 mL and 113 mL, respectively, when compared with a placebo of black tea 3 grams daily and when compared with a control group not assigned to any tea or galactagogues (112863).
• Lice. Topical anise has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children 6-14 years of age shows that application of a topical spray containing anise oil, coconut oil, and ylang ylang oil three times at 5-day intervals is 92% effective for the treatment of head lice and seems to be comparable in effectiveness to a spray containing permethrin, malathion, piperonyl butoxide, and isododecane (13483).
• Menopausal symptoms. It is unclear if oral anise seed extract is beneficial in patients with menopausal symptoms. Details: A small clinical study in postmenopausal adults shows that taking anise seed extract 330 mg three times daily for 4 weeks reduces the frequency and severity of hot flashes by approximately 75% when compared with placebo (94948).
• Migraine headache. It is unclear if topical anise essential oil is beneficial in patients with migraine headache. Details: A small clinical study in adults with migraine headache shows that applying 2 mL of a cream containing anise essential oil 7% to the temporal and forehead zones at the onset of a migraine reduces the impact of the headache by approximately 10% when compared with a control cream. However, there was no effect of the anise cream on analgesic use or average headache severity when compared with placebo cream. Additionally, due to the strong smell of the anise cream, patient blinding may have been compromised (100166).
• Premenstrual syndrome (PMS). It is unclear if oral anise extract is beneficial in patients with PMS. Details: A small clinical study in female college students with PMS shows that taking anise extract 110 mg three times daily, starting 7 days before menstruation and ending 3 days after, improves concentration, mood, irritability, sleep, food cravings, and other symptoms of PMS, as measured using the Premenstrual Symptoms Screening Tool, when compared with placebo (103875). More evidence is needed to rate anise for these uses.

(Read more about ANISE)

POSSIBLY EFFECTIVE

• Dyspepsia. Oral caraway in combination with peppermint and possibly other ingredients, seems to reduce symptoms of dyspepsia. It is unclear if oral caraway alone is beneficial. Details: Several small, low-quality clinical studies and a meta-analysis of this research show that taking proprietary combinations of caraway oil 50 mg and peppermint oil 90 mg (Enteroplant or Menthacarin, Dr Willmar Schwabe GmbH & Co.), 1-3 times daily for 4 weeks, improves quality of life and reduces symptoms of dyspepsia, including feelings of fullness, pain, and mild gastrointestinal (GI) spasms, when compared with placebo (6740,6741,10075,96344,102600). A meta-analysis of three of these clinical studies shows that taking this combination product 2-3 times daily for 4 weeks modestly reduces abdominal pain when compared with placebo (110091). This combination appears to be comparable to cisapride for relieving dyspepsia (6740,6741,10075). It also improves postprandial distress syndrome and epigastric pain syndrome, two subtypes of dyspepsia, when compared with placebo (96344). Another small clinical study in patients with functional dyspepsia shows that taking a combination of caraway oil 50 mg and L-menthol 41.4 mg (equivalent to 100 mg peppermint oil), in a microsphere formulation that releases the oils in the duodenum (FDgard, IM HealthScience LLC), twice daily for 28 days reduces symptoms of postprandial distress syndrome within 24 hours and reduces severe symptoms of epigastric pain syndrome at 28 days when compared with placebo. However, when all patients with functional dyspepsia are considered, symptom scores are not significantly different than placebo at 28 days (103161). Another specific combination product containing caraway, peppermint leaf, clown's mustard plant, German chamomile, licorice root, milk thistle, angelica, celandine, and lemon balm (Iberogast, Steigerwald Arzneimittelwerk GmbH) has also been evaluated in patients with dyspepsia, with promising results (7049). A meta-analysis of three small clinical studies using this combination product shows that taking 1 mL three times daily for 4 weeks reduces severity of acid reflux, epigastric pain, cramping, nausea, and vomiting when compared with placebo (13089). Other clinical research in patients with dyspepsia shows that taking a similar combination product (STW 5-II, Steigerwald Arzneimittelwerk GmbH) that does not contain milk thistle, angelica, or celandine as 1 mL three times daily for up to 8 weeks eliminates gastrointestinal symptoms in 40% more patients when compared with placebo (12724). It is unclear if these findings are due to caraway, other ingredients, or the combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Amenorrhea. Although there has been interest in using oral caraway for amenorrhea, there is insufficient reliable information about the clinical effects of caraway for this purpose.
• Asthma. Oral caraway has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with allergic asthma shows that drinking one cup of tea containing caraway along with anise, black seed, saffron, cardamom, chamomile, fennel, and licorice twice daily for 6 months reduces sleep discomfort, cough frequency, and cough intensity when compared with placebo (19056). It is unclear if these findings are due to caraway, other ingredients, or the combination.
• Constipation. Although there has been interest in using oral caraway for constipation, there is insufficient reliable information about the clinical effects of caraway for this purpose.
• Dysmenorrhea. Although there has been interest in using oral caraway for dysmenorrhea, there is insufficient reliable information about the clinical effects of caraway for this purpose.
• Flatulence. Although there has been interest in using oral caraway for flatulence, there is insufficient reliable information about the clinical effects of caraway for this purpose.
• Irritable bowel syndrome (IBS). It is unclear if topical caraway oil is beneficial in patients with IBS. Details: A small, open-label study in patients with IBS shows that applying a heated poultice of caraway oil 2% to the abdomen for 20-30 minutes at least once daily for 3 weeks modestly improves the severity of IBS symptoms when compared with applying a nonheated, olive oil poultice. However, the improvement may not be clinically meaningful. Also, the heated caraway oil poultice is not more effective than a heated olive oil poultice. This suggests that any possible benefit might relate to the application of heat rather than caraway oil (94085).
• Obesity. It is unclear if oral caraway seed extract is beneficial in patients with obesity. Details: A small clinical study in physically active overweight and obese females shows that taking 30 mL of an aqueous extract providing about 3 grams of caraway seed once daily prior to lunch for 3 months decreases body weight by about 2 kg, body mass index by 0.84 kg/m², percent body fat by 0.7%, and waist circumference by 6 cm, and increases percent muscle mass by 0.19%, when compared to baseline (94088). These improvements are significant when compared with placebo; however, they might not be considered clinically meaningful. Taking caraway seed aqueous extract does not appear to improve blood pressure or lipid levels in these patients (94086). More evidence is needed to rate caraway for these uses.

(Read more about CARAWAY)

POSSIBLY EFFECTIVE

• Dysmenorrhea. Taking fennel oil or extract by mouth may reduce pain in patients with primary dysmenorrhea. This benefit may be similar to ibuprofen or mefenamic acid. Details: Two separate meta-analyses in patients with primary dysmenorrhea show that taking fennel oil or fennel extract for 1-6 menstrual cycles reduces dysmenorrhea pain when compared with placebo. Improvement in pain was similar when compared with ibuprofen or mefenamic acid. In the included studies, doses of fennel oil ranged from 3-30 drops every 4-8 hours, and doses of fennel extract ranged from 30-230 mg daily (104196,108972). However, most studies included in these meta-analyses were small and low-quality, and all studies were conducted in Iran. Higher quality studies in other geographic locations are needed to confirm these findings.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. Although there has been interest in using oral fennel for anxiety, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Bronchitis. Although there has been interest in using oral fennel for bronchitis, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Cancer. Although there has been interest in using oral fennel for cancer prevention, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Cholera. Although there has been interest in using oral fennel for cholera, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Colic. Small clinical studies suggest that oral fennel may reduce crying time in infants with colic. However, most research to date has evaluated fennel in combination with other ingredients. Details: A meta-analysis of three small clinical studies shows that giving fennel to infants with colic can reduce crying time by about 72 minutes daily when compared with placebo (97497). However, the studies included in this meta-analysis were at medium to high risk of bias, and the placebo response rate was high in all of the included studies. Additionally, two of the three studies evaluated combination products (16735,19715,49428). In the one study that used fennel alone, administering 5-20 mL of fennel seed oil 0.1% emulsion daily for one week led to colic relief in 65% of infants, compared with 24% of infants receiving placebo (49428). The other studies evaluated fennel in combination with lemon balm and German chamomile (ColiMil) or in combination with chamomile, vervain, licorice, and lemon balm (Calma-Bebi, Bonomelli). These combination products produced a response in 57% to 85% of infants, compared with 26% to 49% of infants receiving placebo (16735,19715).
• Constipation. Oral fennel has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small crossover trial in patients with constipation shows that drinking an herbal tea containing 3 grams of a combination of fennel, anise, elderberry, and senna daily for 5 days can decrease colonic transit time, increase the number of daily evacuations, and improve the perception of bowel function when compared with placebo (49494). Another small clinical study in elderly patients with constipation shows that drinking a specific tea (Smooth Move, Traditional Medicinals) containing fennel, senna, licorice, orange peel, cassia cinnamon, coriander, and ginger for 28 days can increase the number of bowel movements when compared to baseline (46196). The validity of this finding is limited by the lack of a comparator group. Additionally, a small clinical study in patients aged 60-65 years with functional constipation shows that taking a traditional Iranian combination product containing 5 grams each of fennel seed and rose flower, dissolved in water twice daily before meals for 4 weeks, improves constipation severity and stool consistency when compared with polyethylene glycol 10 grams. Improvements in constipation severity persisted in both groups 4 weeks after treatment completion (108973). However, polyethylene glycol is usually taken at a higher dose of 17 grams daily, limiting the validity of these findings.
• Cough. Although there has been interest in using oral fennel for cough, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Dementia. Although there has been interest in using oral fennel for dementia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Diabetes. Although there has been interest in using oral fennel for diabetes, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Dyspepsia. Although there has been interest in using oral fennel for dyspepsia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Flatulence. Although there has been interest in using oral fennel for flatulence, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Hirsutism. It is unclear if topical fennel is beneficial in patients with hirsutism. Details: A small clinical study in females with male pattern body hair due to unknown causes shows that applying a fennel 2% cream twice daily for 12 weeks can reduce hair diameter by approximately 19% when compared with placebo (49429).
• Insomnia. Although there has been interest in using oral fennel for insomnia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Irritable bowel syndrome (IBS). Oral fennel has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults with either diarrhea- or constipation-predominant IBS shows that taking two capsules containing fennel essential oil 25 mg and curcumin 42 mg per capsule (CU-FEO, Alfa Wassermann S.p.A.) twice daily for 30 days improves overall ratings of abdominal pain, abdominal distention, and quality of life by 24% when compared with placebo (97422).
• Lactation. Although there has been interest in using oral fennel to stimulate breastmilk production, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Menopausal symptoms. Small clinical studies suggest that oral fennel oil or fennel seed powder may modestly improve menopausal symptoms. Details: One small clinical trial in adults with medium severity menopausal symptoms shows that taking fennel essential oil 60 mg daily for 8 weeks improves scores on the Menopause Rating Scale when compared with a sunflower oil placebo (97498). Another small clinical study in postmenopausal adults shows that taking fennel seed powder 2 grams daily for 8 weeks improves scores on the Kupperman Menopausal Index when compared with placebo (104198). Fennel has also been evaluated in combination with other ingredients. One small clinical study shows that taking a combination of fennel 120 mg, chamomile 1000 mg, and saffron 60 mg daily for 12 weeks reduces physical, psychological, and urogenital symptom scores on the Menopause Rating Scale when compared with placebo or lower doses of the combination (103628). Additionally, a moderate-sized clinical study in postmenopausal women conducted in Iran shows that taking combined fennel and valerian extract 500 mg twice daily for 8 weeks modestly improves self-reported scores for frequency and severity of hot flashes but does not improve sleep quality or duration of hot flashes when compared with placebo (112369). However, it is unclear if these benefits are due to fennel, other ingredients, or the combination.
• Nausea and vomiting. Although there has been interest in using oral fennel for nausea and vomiting, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Nocturnal enuresis. Although there has been interest in using oral fennel for nocturnal enuresis, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Osteoarthritis. It is unclear if oral fennel extract is beneficial in patients with knee osteoarthritis. Details: A small clinical trial in females with osteoarthritis of the knee shows that taking powdered fennel extract 800 mg daily for 2 weeks reduces pain and disability scores, but not stiffness, when compared with placebo (104199).
• Polycystic ovary syndrome (PCOS). It is unclear if oral fennel is beneficial in patients with PCOS. Details: A small clinical study in patients with PCOS shows that taking two fennel capsules, containing anethole 21-27 mg per capsule, daily along with a hypocaloric standard diet or a hypocaloric high-protein diet for 3 months does not reduce body weight or improve androgenic parameters such as testosterone levels, sex hormone-binding globulin levels, or free androgen index, when compared with these diets plus placebo (104197). Fennel has also been evaluated in combination with other ingredients. A clinical study in patients with oligomenorrhea due to PCOS shows that taking a traditional combination product (Aslagh) containing equivalent amounts of essential oils of fennel, wild carrot seeds, and Vitex agnus-castus fruit for 3 months, either alone or in combination with metformin, improves rates of menstrual bleeding and menstrual cyclicity similarly to metformin alone. All three groups experienced a significant improvement from baseline. Aslagh was taken as two, 500-mg capsules twice daily, except during menses; metformin was titrated over one week to a dose of 500 mg three times daily (108974). Additionally, a moderate-sized clinical study in patients with PCOS shows that taking fennel 60 mg and Elwendia persica 25 mg twice daily for 4 months modestly improves number of ovarian follicles and body mass index when compared with placebo; however, when compared to baseline, the combination also improves hirsutism scores and menstrual cycle duration and interval (112370). It is unclear if these effects are due to fennel, other ingredients, or the combination.
• Rheumatoid arthritis (RA). Although there has been interest in using oral fennel for RA, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Sexual desire. It is unclear if oral fennel is beneficial for improving sexual desire. Details: A small clinical study in postmenopausal adults shows that taking fennel seed powder 2 grams daily for 8 weeks does not improve scores on the Hurlbert Index of Sexual Desire when compared with placebo (104198).
• Sunburn. It is unclear if topical fennel emulsion is beneficial for preventing sunburn. Details: A small clinical study shows that applying a fennel 5% emulsion topically prior to ultraviolet (UV) exposure can reduce sunburn by 65% when compared with a control (49518).
• Upper respiratory tract infection (URTI). Although there has been interest in using oral fennel for upper respiratory tract infections, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Vaginal atrophy. It is unclear if intravaginal application of fennel cream is beneficial in patients with vaginal atrophy. Details: A small clinical study in postmenopausal adults shows that applying 5 grams of a fennel 5% cream to the vagina once daily for 8 weeks seems to reverse vaginal thinning, improve vaginal pH, and reduce symptoms of vaginal atrophy such as itching, dryness, and pain with intercourse when compared with placebo (92509). Patients in the fennel group also rated their sexual function to be improved when compared with those receiving placebo (97496). More evidence is needed to rate fennel for these uses.

(Read more about FENNEL)

POSSIBLY EFFECTIVE

• Constipation. Glucomannan is generally effective for treatment of constipation in adults, but the efficacy in children is less clear. Details: Clinical research in adults shows that taking glucomannan 1-1.5 grams three times daily orally for 3-5 weeks, sometimes followed by 1 gram twice daily for an additional 4 weeks, can relieve constipation. As a nonabsorbable dietary fiber, glucomannan appears to have a bulk laxative effect (11294,57783,57795,57816). Taking glucomannan 1.45 grams with lactulose 4.2 grams twice daily orally for 1-3 months appears to relieve constipation during pregnancy (57818). In children with constipation, glucomannan can increase the frequency of bowel movements but does not seem to improve stool consistency. A meta-analysis of 3 clinical trials including 122 children with functional constipation shows that glucomannan leads to 1.4 more stools per week but does not improve stool consistency when compared with placebo or a maltodextrin control (97935). Two studies included in this analysis show that taking a specific glucomannan supplement (Dicoplus, Dicofarm) 100 mg/kg once or twice daily (maximum daily dose 5 grams) along with fluids for up to 12 weeks relieves constipation in children (11295,57775). However, the other clinical study included in the analysis shows that taking a different glucomannan supplement (Dicoman Junior, Vitis Pharma) 1.26 grams twice daily for 4 weeks does not improve constipation in children (92005).
• Diabetes. Limited clinical research suggests that glucomannan may improve glycemic control and lipid profiles in patients with type 2 diabetes. Details: Taking glucomannan orally seems to reduce serum cholesterol and blood glucose levels in patients with type 2 diabetes (183,11357,11359,57791,57797,57798,112702). Most clinical research shows that a glucomannan dose of 3-15 grams daily for 4-12 weeks may reduce fasting blood glucose (183,11357,57791,57797,111225). Eating cookies containing glucomannan 0.5-0.7 grams per 100 kcal for 3 weeks has also been used (11358,11359,57797). Accordingly, a meta-analysis of 5 mostly small, low-quality clinical studies in adults with type 2 diabetes, that includes several of these studies, shows that taking glucomannan 1.2-15 grams daily for 4-16 weeks modestly improves fasting blood glucose when compared with placebo or wheat bran. This analysis also shows that taking glucomannan modestly improves 2-hour post-prandial glucose, total cholesterol, and low-density lipoprotein (LDL) levels but not triglycerides (112702). In healthy people, adding a specific glucomannan supplement (PolyGlycopleX, InovoBiologic Inc.) as granules, 2.5-7.5 grams before meals, or as capsules 3-6 grams with meals, can reduce the glycemic index of starchy foods (92003,92007). Also, taking this glucomannan product reduces postprandial glucose in a dose-dependent fashion in healthy people (92002,92007). However, the interpretation of this evidence is limited by low-quality research and variations in dosages and formulations.
• Hyperlipidemia. Most clinical research shows that glucomannan can reduce cholesterol levels in healthy people and those with hyperlipidemia. Details: Although some conflicting evidence exists (57794), most research shows that taking glucomannan orally can improve lipid levels in healthy adults, children and adults with hyperlipidemia, and adults with diabetes (178,11357,11358,11359,57779,57781,57784,57791,57799,97936)(112702). Meta-analyses of clinical research show that taking glucomannan 2.5-15.1 grams daily for up to 12 weeks can reduce total cholesterol by 19 mg/dL, low-density lipoprotein (LDL) cholesterol by 13-16 mg/dL, non-high-density lipoprotein cholesterol by 12 mg/dL, and triglycerides by 11 mg/dL when compared with a control (57797,97936). Clinical research has not demonstrated a dose-response relationship, and the most common glucomannan doses are 5-10 grams daily for up to 6 weeks for adults and 2-3 grams daily in divided doses for up to 8 weeks for children (11358,11359,57797,97936).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Dumping syndrome. It is unclear if oral glucomannan is beneficial in patients with dumping syndrome. Details: Preliminary clinical research shows that taking glucomannan (Propol, Pharmacia) 2.6 or 5.2 grams as a single dose reduces the incidence of reactive hypoglycemia following an oral glucose load in adult patients with previous gastric surgery (57805). Other preliminary clinical research shows that taking glucomannan improves glucose tolerance, but not glucose absorption, in children experiencing gastric dumping syndrome after gastric surgery (57804).
• Hypertension. It is unclear if oral glucomannan is beneficial in patients with hypertension. Details: Preliminary clinical research in patients with hypertension shows that eating cookies containing 0.7 grams of glucomannan per 100 kcal, for a total dose of up to 13 grams of glucomannan daily for 3 weeks, can lower systolic blood pressure by about 7% when compared with placebo (11359).
• Hyperthyroidism. It is unclear if oral glucomannan is beneficial in patients with hyperthyroidism. Details: Preliminary clinical research in patients with hyperthyroidism shows that taking glucomannan 1.3 grams twice daily orally, plus methimazole and propranolol for 2 months, reduces serum triiodothyronine (T3) and thyroxine (T4) levels during the first few weeks of therapy, when compared with methimazole and propranolol alone. However, these effects seem to diminish after 6 weeks of therapy (57793).
• Metabolic syndrome. It is unclear if oral glucomannan is beneficial for metabolic syndrome. Details: A small crossover study in adults with metabolic syndrome, defined as impaired glucose tolerance, reduced high-density lipoprotein (HDL) cholesterol, elevated serum triglycerides, and moderate hypertension, shows that consuming biscuits containing glucomannan 0.5 grams per 100 kcal (equivalent to approximately 8-13 grams/day) daily for 3 weeks may modestly improve fasting glucose, but does not improve blood pressure or levels of triglycerides or HDL cholesterol when compared with wheat bran biscuits (11358). However, the 2-week washout period between interventions may be too short to detect differences in some outcomes.
• Obesity. Although some low-quality research shows that oral glucomannan is beneficial for achieving slight improvements in body weight, other research does not support this. Details: Meta-analyses of clinical research on the use of glucomannan for improving body weight and body composition in adults and children with overweight or obesity show mixed results, with one analysis suggesting that taking glucomannan reduces body weight by around 0.8 kg when compared with placebo (57797), and another showing no improvement in body weight (92014). Reasons for these discrepant findings are not clear, but the discrepancies may relate to differences in the study populations and dosing and duration of glucomannan treatment, as well as the low methodological quality of many studies conducted to date. Similar to the pooled analyses described above, individual clinical study results are also mixed. Several small clinical studies show that taking glucomannan can improve body weight, body mass index (BMI), fat mass, and other measures of body composition in children and adults with overweight or obesity, usually when used in combination with a calorie-restricted diet (180,181,182,183,54240,92008,92010,92011,111224,112701). However, conflicting evidence exists (179,57784,57790,57796,92009,112430). Doses that have been used with positive outcomes in adults are 3-4 grams daily, taken in divided doses, for up to 3 months (181,182,183,92008,112701). In children, doses were 2-3 grams daily for 4 months (180). Specific products evaluated include Propylene TM (Natural Alternatives International), PolyGlycopleX (InovoBiologic, Inc.) 3-5 grams 2-3 times daily for 15 weeks, and. Chrombalance 338 mg before each meal and 226 mg in the afternoon daily for 5 weeks (54240,92010,92011). More evidence is needed to rate glucomannan for these uses.

(Read more about GLUCOMANNAN)

POSSIBLY EFFECTIVE

• Cachexia. Intravenous MCTs can provide calories in critically ill patients and patients with refractory cachexia, but do not seem to offer any advantages over long chain triglycerides. Details: Several small clinical studies in critically ill patients and patients with refractory cachexia secondary to cancer show that receiving parenteral nutrition with a 1:1 mixture of MCTs and long chain triglycerides is similarly effective to long chain triglycerides alone for improving metabolic parameters or nutritional status (2275,2276,93739).

POSSIBLY INEFFECTIVE

• HIV/AIDS-related wasting. Oral MCTs do not seem to promote weight gain or prevent weight loss in patients with HIV infection. Details: A large clinical study in patients with HIV infection shows that taking a peptide-based supplement containing MCTs (Peptamen Oral Complete Elemental Diet, Nestlé Clinical Nutrition) with multivitamins and minerals is no more effective than taking multivitamins and minerals alone for promoting weight gain or preventing weight loss (11730).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. It is unclear if oral MCTs are beneficial in patients with age-related cognitive decline. Details: A small, single-blind clinical study in older adults residing in a nursing home shows that taking MCTs 6 grams (a 3:1 mixture of caprylic acid:capric acid), with or without L-leucine 1.2 grams and vitamin D (cholecalciferol) 20 mcg, daily for up to 3 months increases mini-mental state exam (MMSE) scores by an average of 3.5 points, compared with a 0.7-point decline in those receiving a long chain triglyceride control. MMSE scores returned to baseline 1.5 months after discontinuation of MCT supplementation (105710).
• Alzheimer disease. Small clinical studies suggest that oral MCTs do not improve cognition in patients with Alzheimer disease or mild cognitive impairment. Details: A meta-analysis of small clinical studies in patients with Alzheimer disease or mild cognitive impairment shows that taking MCTs (as combinations of caprylic acid and capric acid) in doses of 20-56 grams or 22.5-165 mL daily for up to 6 months does not improve cognition when compared with placebo or baseline (103012).
• Athletic performance. It is unclear if oral MCTs are beneficial for endurance athletic performance. Details: A very small clinical study in 10 male recreational endurance runners shows that taking a ketone supplement containing MCTs and a salt form of beta-hydroxybutyrate 60 minutes prior to a run does not improve 5-kilometer run time when compared with placebo (107738). This study may have been inadequately powered to detect a difference between groups.
• Celiac disease. Although there has been interest in using oral MCTs for celiac disease, there is insufficient reliable information about the clinical effects of MCTs for this purpose.
• Chylothorax. It is unclear if oral MCTs improve time to resolution of spontaneous congenital chylothorax in neonates. Details: A small retrospective study in neonates with spontaneous congenital chylothorax shows that administering MCTs does not improve the time to resolution of chylothorax when compared with total parenteral nutrition (11729).
• Chyluria. Although there has been interest in using oral MCTs for chyluria, there is insufficient reliable information about the clinical effects of MCTs for this purpose.
• Cystic fibrosis. Although there has been interest in using oral MCTs for cystic fibrosis, there is insufficient reliable information about the clinical effects of MCTs for this purpose.
• Diabetes. Although there has been interest in using oral MCTs for diabetes, there is insufficient reliable information about the clinical effects of MCTs for this purpose.
• Epilepsy. It is unclear if oral MCTs are beneficial in adults and adolescents aged 12 years or older with drug-resistant epilepsy. Details: A small clinical study in adults and adolescents aged 12 years or older with drug-resistant epilepsy shows that adjunctive treatment with MCTs (Stepan Lipid Nutrition) as part of a non-ketogenic diet, 47-65 mL daily (about 35% of energy intake), or a maximally tolerated dose not exceeding 100 mL, for 12 weeks reduces median seizure frequency by 46% when compared with baseline (101967). The validity of this study is limited by its small sample size and the lack of a comparator group.
• Gallbladder disease. Although there has been interest in using oral MCTs for gallbladder disease, there is insufficient reliable information about the clinical effects of MCTs for this purpose.
• Hypertriglyceridemia. Oral MCTs might improve triglyceride levels and body weight in some patients with overweight and hypertriglyceridemia, but its effect in other populations is unclear. Details: Clinical research in patients with overweight and hypertriglyceridemia shows that taking 25-30 grams of an oil containing MCTs 13% daily for 8 weeks decreases triglyceride levels by 78 mg/dL when compared with consuming oil containing only long chain fats. Body weight, body fat, and waist circumference also decreased (93740). However, this benefit may be restricted to this specific population only. Some research in patients with obesity or patients with a normal body weight shows that taking 25-30 grams of an oil containing MCTs daily for 8 weeks does not lower triglyceride levels (93741).
• Obesity. Small clinical studies suggest that oral MCTs modestly improves weight loss; however, any effects may not be clinically relevant. Details: A meta-analysis of clinical research shows that taking MCTs decreases body weight by 0.5 kg, waist circumference by 1.5 cm, and hip circumference by 0.8 cm when compared with a control group not taking MCTs. Doses used in available research have ranged from 1-54 grams daily, or 1% to 24% of energy for 4-16 weeks (93735). Most research shows that at least 4 weeks is needed before effects are seen. The greatest benefit seems to occur in patients of Asian descent, males, and patients with higher body mass indices at baseline (93730,93731,93735,93736). While MCTs may improve weight loss in some patients, the effects are generally modest and may not be clinically relevant.
• Prematurity. It is unclear if oral or topical MCTs are beneficial in preterm infants. Details: A meta-analysis of small studies involving 136 otherwise healthy preterm infants receiving full enteral diets with formula as the predominant source of nutrition shows that administration of formulas containing at least 30% of fat by weight as MCTs (ranging in concentration from 6% to 80%) for at least 7 days does not affect short-term growth, including weight, length, and head circumference, when compared with formulas containing less than 30% of fat by weight as MCTs. Due to small study sizes, it is unclear whether either type of formula was better tolerated. The validity of this analysis is limited by the presence of unclear risk of potential bias in the included studies (105711). MCT oil has also been evaluated for the prevention of gastrointestinal Candida infections. A very small clinical study in preterm infants shows that adding MCT oil (Nestlé Health Science) 0.5 mL per ounce of formula or breast milk for 1 week reduces Candida colonization when compared with no MCT oil (101968). Topical use of MCT oil has also been evaluated for growth in preterm infants. A small clinical study in preterm infants weighing 1500-2000 grams shows that massage with MCT oil, consisting of tactile and kinesthetic stimulation, three times daily for 7 days increases weight gain when compared with no massage (107739). The validity of this finding is limited by unclear reporting. Also, it is unclear if this effect is due to MCT oil, massage, or the combination.
• Primary intestinal lymphangiectasia. It is unclear if oral MCTs are beneficial for the management of primary intestinal lymphangiectasia. Details: A review of 55 case reports suggests that taking MCTs as part of a low-fat, high-protein diet resolves symptoms in 63% of patients with primary intestinal lymphangiectasia, compared with 36% of patients receiving no treatment or other treatments such as diuretic therapy, albumin transfusions, resection of isolated segments of affected bowels, etc. Mortality is also reduced by 79% in patients treated with diet restrictions and MCTs when compared with those receiving no treatment or other treatments (93733).
• Sarcopenia. It is unclear if oral MCTs are beneficial in frail older adults. Details: A small clinical study in older adults residing in a nursing home shows that taking MCTs 6 grams, leucine 1.2 grams, and vitamin D (cholecalciferol) 20 mcg daily for 3 months increases body weight by 1.1 kg, right-hand grip strength by 13%, and peak expiratory flow by 28% when compared with baseline. These improvements are also significant when compared with patients receiving no supplementation (93729). In a second study in this same population conducted by the same research group, taking MCTs 6 grams, with or without leucine 1.2 grams and vitamin D (cholecalciferol) 20 mcg, daily for 3 months does not increase body weight or hand grip strength. There were small to moderate improvements in opening and closing the legs, repetitive swallowing, and measures of functional independence (101970). The validity of these findings is limited by the single-blind nature of the studies and the large number of endpoints. It is also unclear if any benefits are due to MCTs, other ingredients, or the combination.
• Short bowel syndrome. Although there has been interest in using oral MCTs for short bowel syndrome, there is insufficient reliable information about the clinical effects of MCTs for this purpose. More evidence is needed to rate MCTs for these uses.

(Read more about MEDIUM CHAIN TRIGLYCERIDES (MCTs))

LIKELY EFFECTIVE

• Cystic fibrosis. Long-term nebulized hypertonic sodium chloride improves lung function and reduces pulmonary exacerbations in patients with cystic fibrosis. Details: Meta-analyses of clinical research in adults with cystic fibrosis show that, when taken along with a bronchodilator and other standard therapies, nebulized hypertonic sodium chloride in concentrations of 3% to 7%, up to 10 mL twice daily for 4 weeks, increases forced expiratory volume at one second (FEV1) when compared with isotonic saline (sodium chloride 0.9%) (26230,26230). This benefit was not seen at 48 weeks. Other clinical research in adults with cystic fibrosis shows that inhaling sodium chloride 7%, 4 mL twice daily for 48 weeks, does not improve FEV1 when compared with isotonic saline. However, chronic treatment with hypertonic saline does reduce the number of pulmonary exacerbations and increase the number of patients without pulmonary exacerbations when compared with isotonic saline (29402). It is not clear if this benefit occurs in children with cystic fibrosis. The Pulmonary Clinical Practice Guidelines Committee of the Cystic Fibrosis Foundation recommends that individuals with cystic fibrosis aged 6 years or older use nebulized hypertonic saline long-term to improve lung function, reduce the number of exacerbations, and improve quality of life (29403).

POSSIBLY EFFECTIVE

• Amphotericin B nephrotoxicity. Oral sodium chloride seems to prevent nephrotoxicity associated with use of amphotericin B. Details: Clinical research shows that administering oral or intravenous sodium chloride 150 mEq daily during treatment with amphotericin B can attenuate the rise in serum creatinine levels and preserve renal function when compared to treatment with amphotericin B alone (26226).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Bipolar disorder. It is unclear if oral sodium is beneficial in preventing lithium level fluctuations in patients with bipolar disorder. Details: A moderate-sized open-label clinical study in adults with type I bipolar disorder receiving lithium carbonate shows that taking sodium chloride 1 gram daily for 12 weeks along with dietary salt restriction of 1 gram daily reduces the percentage of patients with lithium level fluctuations above 0.8 mEq/L, but does not significantly affect serum sodium, potassium, aldosterone, or creatinine levels when compared with controls who were not salt restricted, but were advised not to consume additional salt at the table (112909). However, the interpretation of these findings is limited by missing data in both groups.
• Canker sores. Although there is interest in using topical sodium chloride for canker sores, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Congestive heart failure. It is unclear if oral sodium is beneficial in patients with acute decompensated heart failure requiring decongestive therapy with diuretics. Details: A moderate-sized clinical study in adults hospitalized with acute decompensated heart failure requiring high-dose intravenous furosemide shows that taking sodium chloride 2 grams three times daily for up to 96 hours does not affect patient weight or serum creatinine levels when compared with placebo (112911). However, the clinical relevance of this study is unclear and it may have been inadequately powered to detect a difference between groups.
• Conjunctivitis. Although there is interest in using ophthalmic sodium chloride for conjunctivitis, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Hyponatremia. Although there is interest in using oral sodium chloride for hyponatremia, there is insufficient reliable information about the clinical effects of oral sodium chloride for this condition.
• Pharyngitis. Although there is interest in using topical sodium chloride for pharyngitis, there is insufficient reliable information about the clinical effects of sodium chloride for this condition.
• Prematurity. It is unclear if oral sodium is beneficial for premature infants. Details: Preliminary clinical research in infants born at less than 32 weeks' gestation shows that adding sodium 4 mEq/kg daily to enteral feedings, starting from the 7th day after birth and continuing through the 35th day, reduces the risk of developing hyponatremia and improves weight gain when compared with adding water (98180). A small, open-label clinical study in newborns less than 35 weeks gestation shows that high sodium intake, defined as an average of 0.25% sodium in maintenance fluids, for 48 hours on day 2 and 3 after birth results in less weight loss within the first 72 hours of life when compared with control, but does not improve mortality, length of hospital stay, or complications from prematurity (112908). However, interpretation of these findings is limited by varied concentrations of sodium as an intervention. More evidence is needed to rate sodium for these uses.

(Read more about SODIUM)

POSSIBLY EFFECTIVE

• Constipation. Taking xanthan gum orally as a bulk-forming laxative seems to decrease constipation (4917,4918).
• Swallowing dysfunction. Using a specific xanthan gum product (Resource ThickenUp Clear, Nestle Health Science) as a thickener in liquid feeds improves swallowing and reduces the risk of aspiration in people with swallowing dysfunction similarly to a modified starch thickener (Resource ThickenUp, Nestle Health Science). Xanthan gum also does not appear to leave the pharyngeal residues seen with the modified starch product (100912,100913).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Diabetes. Taking xanthan gum 12 grams orally daily in muffins seems to lower blood glucose in people with diabetes (4916).
• Dry eye. Using eye drops containing xanthan gum and chondroitin sulfate (PRO-148 or Xiel ofteno, Sophia Laboratories) four times daily for 60 days improves tear film break-up times, ocular surface disease index, and symptoms of dry eye similarly to polyethylene glycol/propylene glycol eye drops (Systane, Alcon Laboratories Inc.) (89591,95794). It is not clear if this effect is due to xanthan gum, chondroitin sulfate, or the combination.
• Sjogren syndrome. Applying xanthan gum topically in the mouth seems to help as a saliva substitute in people with Sjogren syndrome (4915).

(Read more about XANTHAN GUM)

LIKELY SAFE ...when used orally in amounts typically found in foods (11). There is insufficient reliable information available about the safety of algin when used orally in medicinal amounts.

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

(Read more about ALGIN)

LIKELY SAFE ...when used orally in amounts commonly found in food. Anise and anise oil have Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when anise powder is used orally and appropriately in medicinal amounts. Anise powder has been used with apparent safety in clinical research at doses of up to 9 grams daily for up to 4 weeks (94944,94945). ...when anise oil is used orally and appropriately in medicinal amounts. Anise oil has been used with apparent safety in clinical research at doses of up to 600 mg daily for up to 4 weeks (94946,94947).

CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in food. Anise and anise oil have Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of anise when used by children in medicinal amounts.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in food. Anise and anise oil have Generally Recognized as Safe (GRAS) status in the US (4912). There is insufficient reliable information available about the safety of anise when taken orally in medicinal amounts during pregnancy or breast-feeding.

(Read more about ANISE)

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

POSSIBLY SAFE ...when caraway oil is used orally in medicinal amounts. Caraway oil has been used with apparent safety at a dose of up to 150 mg daily for up to 4 weeks, in combination with peppermint oil (6740,6741,6742,10075,96344). ...when caraway seed is used orally, short-term. An aqueous caraway seed extract has been used with apparent safety at a dose of 3 grams daily for up to 3 months (94086,94087,94088). ...when used topically and appropriately. A heated poultice containing caraway oil 2% has been used with apparent safety for up to 3 weeks (94085).

PREGNANCY: POSSIBLY UNSAFE
when used in medicinal amounts (4912,6746). Caraway oil has been used to stimulate menstruation (6746); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

(Read more about CARAWAY)

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

POSSIBLY SAFE ...when fennel essential oil or extract is used orally and appropriately, short-term. Twenty-five drops (about 1.25 mL) of fennel fruit extract standardized to fennel 2% essential oil has been safely used four times daily for 5 days (49422). Also, two 100 mg capsules each containing fennel 30% essential oil standardized to 71-90 mg of anethole has been safely used daily for 8 weeks (97498). Powdered fennel extract has been used with apparent safety at a dose of 800 mg daily for 2 weeks (104199). ...when creams containing fennel 2% to 5% are applied topically (49429,92509).

CHILDREN: POSSIBLY SAFE
when combination products containing fennel are used to treat colic in infants for up to one week. Studied products include up to 20 mL of a fennel seed oil emulsion; a specific product (ColiMil) containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg; and up to 450 mL of a specific tea (Calma-Bebi, Bonomelli) containing fennel, chamomile, vervain, licorice, and lemon balm (16735,19715,49428).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Observational research has found that regular use of fennel during pregnancy is associated with shortened gestation (100513).

LACTATION: POSSIBLY UNSAFE
when used orally. Case reports have linked consumption of an herbal tea containing extracts of fennel, licorice, anise, and goat's rue to neurotoxicity in two breast-feeding infants. The adverse effect was attributed to anethole, a constituent of fennel and anise (16744). However, levels of anethole were not measured in breastmilk, and the herbal tea was not tested for contaminants. Furthermore, other adverse effects related to use of fennel during lactation have not been reported. However, until more is known, avoid using.

(Read more about FENNEL)

LIKELY SAFE ...when used orally as food (11358,11359). Glucomannan powder or flour is often used to enrich noodles in traditional Japanese foods.

POSSIBLY SAFE ...when used orally with at least 250 mL (8 ounces) of water or other fluid. Glucomannan has been safely used in studies lasting up to 4 months (178,179,181,182,11046,11294,11357,11294,54240,57775)(57781,57783,57784,92004,92008,92009,92010,92011,106410). In the European Union, the maximum permitted level in foods is 10 grams/kg (106411).

POSSIBLY UNSAFE ...when used orally without any liquid, especially when in tablet form. There have been reports of choking and esophageal or gastrointestinal obstruction when glucomannan products are taken dry. A safety alert for this has been issued by Health Canada (11293,57785,106410).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately with at least 250 mL (8 ounces) of water or other fluid. Glucomannan has been safely used in children for up to 4 months (179,180,11295,57775,57779,92005,92006,97935).

CHILDREN: LIKELY UNSAFE
when used orally without any liquid, especially when in tablet form. There have been reports of esophageal and gastrointestinal obstruction when glucomannan products are taken dry (11293,57785,106410).

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

(Read more about GLUCOMANNAN)

LIKELY SAFE ...when used orally and appropriately (11726,11727,11728,11729,11730,93729). ...when used parenterally and appropriately (2275,2276,2278,11726,11727,11728,11729). There is insufficient reliable information available about the safety of MCTs when used topically.

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

(Read more about MEDIUM CHAIN TRIGLYCERIDES (MCTs))

LIKELY SAFE ...when used orally and appropriately. Sodium is safe in amounts that do not exceed the Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams daily (100310). Higher doses can be safely used therapeutically with appropriate medical monitoring (26226,26227).

POSSIBLY UNSAFE ...when used orally in high doses. Tell patients to avoid exceeding the CDRR intake level of 2.3 grams daily (100310). Higher intake can cause hypertension and increase the risk of cardiovascular disease (26229,98176,98177,98178,98181,98183,98184,100310,109395,109396,109398,109399). There is insufficient reliable information available about the safety of sodium when used topically.

CHILDREN: LIKELY SAFE
when used orally and appropriately (26229,100310). Sodium is safe in amounts that do not exceed the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310).

CHILDREN: POSSIBLY UNSAFE
when used orally in high doses. Tell patients to avoid prolonged use of doses exceeding the CDRR intake level of 1.2 grams daily for children 1 to 3 years, 1.5 grams daily for children 4 to 8 years, 1.8 grams daily for children 9 to 13 years, and 2.3 grams daily for adolescents (100310). Higher intake can cause hypertension (26229).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately. Sodium is safe in amounts that do not exceed the CDRR intake level of 2.3 grams daily (100310).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in higher doses. Higher intake can cause hypertension (100310). Also, both the highest and the lowest pre-pregnancy sodium quintile intakes are associated with an increased risk of hypertensive disorders of pregnancy, including gestational hypertension and pre-eclampsia, and the delivery of small for gestational age (SGA) infants when compared to the middle intake quintile (106264).

(Read more about SODIUM)

LIKELY SAFE ...when consumed in amounts found in foods, up to 10 mg/kg per day (4914). It has Generally Recognized as Safe (GRAS) status in the US (4912). ...when used orally for medicinal use in amounts up to 15 grams per day (4914,4916,4917,4918). ...when used topically and appropriately (4914,89591,95794).

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

(Read more about XANTHAN GUM)

(Read more about ALGIN)

ACETAMINOPHEN (Tylenol, others) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, anise oil might decrease the levels and clinical effects of acetaminophen.  Details Animal research shows that taking anise oil with acetaminophen decreases peak plasma levels of acetaminophen but does not reduce overall bioavailability (94951). Whether this interaction will occur in humans is unclear.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, anise seed might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details A small clinical study shows that anise seed powder decreases fasting blood glucose levels by 36% when compared to baseline (94953).

CAFFEINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, anise oil might decrease the efficacy of caffeine.  Details Animal research shows that taking anise oil with caffeine decreases the bioavailability of caffeine (94951). Whether this interaction will occur in humans is unclear.

CODEINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, anise oil might increase the effects and adverse effects of codeine.  Details Animal research shows that anise oil increases the analgesic effects of codeine, possibly by inducing its phase I metabolism and increasing conversion to morphine (94950). Whether this interaction occurs in humans is unclear.

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, anise might interfere with contraceptive drug therapy.  Details Some in vitro research suggests that anise has estrogenic effects (13506), while other in vitro research suggests that anise has antiestrogenic effects (12728).

DIAZEPAM (Valium) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, anise oil might increase the effects and adverse effects of diazepam.  Details Animal research shows that taking anise oil with diazepam increases the motor impairment associated with diazepam, possibly by inhibiting its breakdown by cytochrome P450 3A4 (94950). Whether this interaction occurs in humans is unclear.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, anise might interfere with estrogen-based hormone replacement therapy.  Details Some in vitro research suggests that anise has estrogenic effects (13506), while other in vitro research suggests that anise has antiestrogenic effects (12728).

FLUOXETINE (Prozac) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, anise oil might decrease the efficacy of fluoxetine.  Details Animal research shows that taking anise oil with fluoxetine reduces the antidepressant effects of fluoxetine, possibly by promoting its breakdown by cytochrome P450 2D6 (94950). Whether this interaction occurs in humans is unclear.

IMIPRAMINE (Tofranil) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, anise oil might decrease the efficacy of imipramine.  Details Animal research shows that taking anise oil with imipramine reduces the antidepressant effects of imipramine, possibly by promoting its breakdown by cytochrome P450 2D6 (94950). Whether this interaction occurs in humans is unclear.

MIDAZOLAM (Versed) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, anise oil might increase the effects and adverse effects of midazolam.  Details Animal research shows that taking anise oil with midazolam increases the motor impairment associated with midazolam, possibly by inhibiting its breakdown by cytochrome P450 3A4 (94950). Whether this interaction occurs in humans is unclear.

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, anise might interfere with tamoxifen therapy.  Details Some in vitro research suggests that anise has estrogenic effects (13506), while other in vitro research suggests that anise has antiestrogenic effects (12728).

(Read more about ANISE)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, caraway might increase the risk of hypoglycemia when used with antidiabetes drugs.  Details Animal research suggests that caraway can reduce blood glucose levels (12736,39844). Monitor blood glucose levels closely. Medication dose adjustments may be necessary.

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, caraway might increase the effects and adverse effects of CNS depressants.  Details Animal research suggests that (S)-(+)-carvone, a major constituent of caraway seed extract, has sedative effects (39800).

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, caraway might increase the levels and clinical effects of CYP1A1 substrates.  Details In vitro evidence suggests that caraway extract can inhibit the activity of CYP1A1 in a dose-dependent manner (39780). This interaction has not been reported in humans.

DIURETIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, caraway might increase the risk of hypokalemia when used with diuretics that deplete potassium.  Details Animal research suggests that a single dose of caraway fruit extract can promote diuresis and increase the urinary excretion of sodium and potassium. However, sub-chronic use of caraway fruit extract does not seem to significantly increase potassium excretion, although urine output continues to be increased for up to 6 days (39797).

ISONIAZID Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, caraway might increase the effects and adverse effects of isoniazid.  Details Animal research suggests that a specific fraction of caraway seed extract (CC-1a) can increase plasma levels of isoniazid when administered concomitantly (25529). 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 Theoretically, caraway might reduce excretion and increase levels of lithium due to diuretic effects.  Details Animal research suggests that caraway fruit extract has diuretic properties (39797).

PYRAZINAMIDE Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, caraway might increase the effects and adverse effects of pyrazinamide.  Details Animal research suggests that a specific fraction of caraway seed extract (CC-1a) can increase plasma levels of pyrazinamide when administered concomitantly (25529). This interaction has not been reported in humans.

RIFAMPIN (Rifadin) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, caraway might increase the effects and adverse effects of rifampin.  Details Animal research suggests that a specific fraction of caraway seed extract (CC-1a) can increase plasma levels of rifampin when administered concomitantly (25529). This interaction has not been reported in humans.

(Read more about CARAWAY)

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fennel might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details Animal research suggests that fennel oil has antithrombotic and antiplatelet effects (31415,49445).

CIPROFLOXACIN (Cipro) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, fennel might decrease the levels and clinical effects of ciprofloxacin.  Details Animal research shows that fennel reduces ciprofloxacin bioavailability by nearly 50%, possibly due to the metal cations such as calcium, iron, and magnesium contained in fennel. This study also found that fennel increased tissue distribution and slowed elimination of ciprofloxacin (6135).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.  Details Some constituents of fennel have estrogenic activity (11).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.  Details In vitro research suggests that fennel inhibits CYP3A4 enzyme activity (38375,49468). This effect has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might interfere with hormone replacement therapy due to competition for estrogen receptors.  Details Some constituents of fennel have estrogenic activity (11).

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might decrease the antiestrogenic effect of tamoxifen.  Details Some constituents of fennel have estrogenic activity (11), which may interfere with the antiestrogenic activity of tamoxifen.

(Read more about FENNEL)

ORAL DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, glucomannan may decrease absorption of drugs taken orally.  Details Due to its viscosity and bulking effects, there is concern that glucomannan can decrease the absorption of oral drugs. A small clinical study in healthy volunteers shows that taking glyburide 2.5 mg plus glucomannan 3.9 grams with breakfast reduces plasma levels of glyburide when compared with breakfast and glyburide alone (11360). In addition, animal research demonstrates this effect on amoxicillin, but shows increased absorption of metronidazole. This mouse model also demonstrates that metronidazole elimination is prolonged, but amoxicillin elimination is enhanced by 38%; glucomannan may also affect the distribution of some drugs (112703). To avoid changes in absorption, take glucomannan 30-60 minutes after taking oral drugs.

(Read more about GLUCOMANNAN)

(Read more about MEDIUM CHAIN TRIGLYCERIDES (MCTs))

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = A Theoretically, a high intake of dietary sodium might reduce the effectiveness of antihypertensive drugs.  Details High intake of dietary sodium can increase systolic and diastolic blood pressure (26222). Also, high intake of sodium may necessitate increased use of antihypertensive medications to achieve blood pressure control in some patients, such as those with chronic kidney disease (26223).

CORTICOSTEROIDS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant use of mineralocorticoids and some glucocorticoids with sodium supplements might increase the risk of hypernatremia.  Details Mineralocorticoids and some glucocorticoids (corticosteroids) cause sodium retention. This effect is dose-related and depends on mineralocorticoid potency. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone (4425).

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Altering dietary intake of sodium might alter the levels and clinical effects of lithium.  Details High sodium intake can reduce plasma concentrations of lithium by increasing lithium excretion (26225). Reducing sodium intake can significantly increase plasma concentrations of lithium and cause lithium toxicity in patients being treated with lithium carbonate (26224,26225). Stabilizing sodium intake is shown to reduce the percentage of patients with lithium level fluctuations above 0.8 mEq/L (112909). Patients taking lithium should avoid significant alterations in their dietary intake of sodium.

SODIUM-CONTAINING DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant use of sodium-containing drugs with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia and long-term sodium-related complications.  Details The Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams of sodium daily indicates the intake at which it is believed that chronic disease risk increases for the apparently healthy population (100310). Some medications contain high quantities of sodium. When used in conjunction with sodium supplements or high-sodium diets, the CDRR may be exceeded. Additionally, concomitant use may increase the risk for hypernatremia; this risk is highest in the elderly and people with other risk factors for electrolyte disturbances.

TOLVAPTAN (Samsca) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Theoretically, concomitant use of tolvaptan with sodium might increase the risk of hypernatremia.  Details Tolvaptan is a vasopressin receptor 2 antagonist that is used to increase sodium levels in patients with hyponatremia (29406). Patients taking tolvaptan should use caution with the use of sodium salts such as sodium chloride.

(Read more about SODIUM)

(Read more about XANTHAN GUM)

General ...Orally, algin is well tolerated in amounts typically found in foods (11). No adverse effects related to medicinal amounts of algin have been reported. However, a thorough evaluation of safety outcomes has not been conducted.

(Read more about ALGIN)

General ...Orally, anise seems to be well tolerated.
Most Common Adverse Effects:
Topically: Contact dermatitis in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.

Dermatologic ...Topically, anise, in combination with other herbs, has been reported to cause localized pruritus (13483).

Immunologic ...Anise can cause allergic reactions in sensitive individuals. Orally or by inhalation, anise can cause rhinoconjunctivitis, occupational asthma, and anaphylaxis (13484). Topically, anise can cause contact dermatitis, rhinitis, and asthma (31319,31341). Contact dermatitis and cheilitis have also been reported following the use of toothpaste containing anethole, a constituent of anise (31403,31528).

(Read more about ANISE)

General ...Orally, caraway oil seems to be well tolerated.

Gastrointestinal ...Orally, caraway oil, when used in combination with peppermint oil, may cause a substernal burning sensation, belching, nausea, and vomiting (6741,6742,10075,96344). It is unclear if these adverse effects are due to caraway oil, peppermint oil, or the combination. Peppermint oil, when used alone, has been reported to cause similar adverse effects.

Immunologic ...Orally, an allergic reaction has been reported after use of caraway oil in combination with peppermint oil in a patient with a history of bronchial asthma (96344). It is unclear if this adverse effect is due to caraway oil, peppermint oil, or the combination.

(Read more about CARAWAY)

General ...Orally and topically, fennel seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, photosensitivity, and allergic reactions in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Seizures.

Dermatologic ...Advise patients to avoid excessive sunlight or ultraviolet light exposure while using fennel (19). Allergic reactions affecting the skin such as atopic dermatitis and photosensitivity may occur in patients who consume fennel (6178,49507).

Gastrointestinal ...Orally, fennel may cause gastrointestinal complaints, including nausea and vomiting (19146,104196).

Hematologic ...Methemoglobinemia has been reported in four infants following intoxication related to ingestion of a homemade fennel puree that may have been made from improperly stored fennel (49444).

Immunologic ...A case report describes an 11-year-old male who developed an allergy to fennel-containing toothpaste. Immediately after using the toothpaste, the patient experienced sneezing, coughing, itchy mouth, rhinorrhea, nasal congestion, wheezing, difficulty breathing, and palpitations, which resolved within 10 minutes of spitting out the toothpaste and rinsing the mouth. In challenge tests, the patient reacted to chewing fresh fennel root, but not ground fennel seeds (103822).

Neurologic/CNS ...Orally, fennel oil has been associated with tonic clonic and generalized seizures (12868). New-onset cluster headaches are reported in a 24-year-old female while using a toothpaste containing fennel and camphor for 3 months. The headaches resolved upon stopping the toothpaste (112368). It is unclear if this adverse effect can be attributed to fennel, camphor, or the combination.

Pulmonary/Respiratory ...Orally, fennel and fennel seed have been reported to cause bronchial asthma (49478).

(Read more about FENNEL)

General ...Orally, glucomannan is generally well tolerated when taken with plenty of water or other liquid.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, constipation, diarrhea, flatulence, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Choking and esophageal or gastrointestinal obstruction, especially when taken as a dry powder or in tablet form.

Gastrointestinal ...Orally, glucomannan can cause gastrointestinal disturbances, including abdominal pain, bloating, constipation, diarrhea, flatulence, nausea, and vomiting, especially when taken in doses of more than 3 grams daily (57781,57784,92004,92010,92011,97935,106411). Esophageal and gastrointestinal obstructions have been reported when dry glucomannan-containing products are taken with insufficient fluid (11293,57785,106410).

Hepatic ...Acute cholestatic hepatitis occurred in a 31-year-old male after taking glucomannan orally for 45 days (57777). He was also taking other supplements, including garlic and chitosan, so it is unclear whether the hepatitis was due to glucomannan, other supplements, or the combination.

Pulmonary/Respiratory ...Cases of occupational respiratory disorders, including respiratory sensitization and bronchial asthma, have been reported in workers exposed to glucomannan (57789,57810).

(Read more about GLUCOMANNAN)

General ...Orally, MCTs can cause significant gastrointestinal upset, especially with higher doses.
Most Common Adverse Effects:
Abdominal discomfort, diarrhea, essential fatty acid deficiency, intestinal gas noises, irritability, nausea, reflux, vomiting. Gastrointestinal disturbances are thought to be associated with higher doses of MCT. Since MCTs are fats, excessive consumption can result in weight gain.

Cardiovascular ...There is some concern that MCTs may further increase the risk for hypertriglyceridemia in some preterm infants due to immature lipoprotein lipase activity in these infants. A case of extremely elevated triglyceride levels of 4,736 mg/dL and associated lipemia retinalis has been reported at 43 weeks post-menstrual age (PMA) for a preterm infant born at 30 weeks' gestational age. It was discovered that the baby had been receiving MCT supplements in addition to breast milk starting at 42 weeks' PMA. MCT supplements were discontinued. One month later triglycerides were reduced to 287 mg/dL, and the retinal vasculature had a normal hue. However, at 2-month follow-up, triglyceride levels were elevated to levels higher than normal for age despite MCT discontinuation. Investigators speculated that a genetic disorder of lipid metabolism may also have contributed to the elevated triglyceride levels in addition to use of MCTs (96330).

Gastrointestinal ...Orally, MCTs can cause significant gastrointestinal upset. Diarrhea is the most commonly reported side effect (11723,93737,93738,101967). Other reported side effects include vomiting, irritability, nausea, reflux, abdominal discomfort, intestinal gas noises, and essential fatty acid deficiency (11723,93738,101967). Taking MCTs with food can reduce these adverse effects (93737). Gastrointestinal disturbances are thought to be associated with higher doses of MCT, such as 85 grams (93731).

Other ...Excessive consumption of MCTs can result in weight gain. MCT oil contains 6-8.5 calories per gram. One tablespoon provides about 14 grams and about 115 calories (11724).

(Read more about MEDIUM CHAIN TRIGLYCERIDES (MCTs))

General ...Orally, sodium is well tolerated when used in moderation at intakes up to the Chronic Disease Risk Reduction (CDRR) intake level. Topically, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Worsened cardiovascular disease, hypertension, kidney disease.

Cardiovascular ...Orally, intake of sodium above the CDRR intake level can exacerbate hypertension and hypertension-related cardiovascular disease (CVD) (26229,98176,100310,106263). A meta-analysis of observational research has found a linear association between increased sodium intake and increased hypertension risk (109398). Observational research has also found an association between increased sodium salt intake and increased risk of CVD, mortality, and cardiovascular mortality (98177,98178,98181,98183,98184,109395,109396,109399). However, the existing research is unable to confirm a causal relationship between sodium intake and increased cardiovascular morbidity and mortality; high-quality, prospective research is needed to clarify this relationship (100312). As there is no known benefit with increased salt intake that would outweigh the potential increased risk of CVD, advise patients to limit salt intake to no more than the CDRR intake level (100310).
A reduction in sodium intake can lower systolic blood pressure by a small amount in most individuals, and diastolic blood pressure in patients with hypertension (100310,100311,106261). However, post hoc analysis of a small crossover clinical study in White patients suggests that 24-hour blood pressure variability is not affected by high-salt intake compared with low-salt intake (112910). Additionally, the available research is insufficient to confirm that a further reduction in sodium intake below the CDRR intake level will lower the risk for chronic disease (100310,100311). A meta-analysis of clinical research shows that reducing sodium intake increases levels of total cholesterol and triglycerides, but not low-density lipoprotein (LDL) cholesterol, by a small amount (106261).
It is unclear whether there are safety concerns when sodium is consumed in amounts lower than the adequate intake (AI) levels. Some observational research has found that the lowest levels of sodium intake might be associated with increased risk of death and cardiovascular events (98181,98183). However, this finding has been criticized because some of the studies used inaccurate measures of sodium intake, such as the Kawasaki formula (98177,98178,101259). Some observational research has found that sodium intake based on a single 24-hour urinary measurement is inversely correlated with all-cause mortality (106260). The National Academies Consensus Study Report states that there is insufficient evidence from observational studies to conclude that there are harmful effects from low sodium intake (100310).

Endocrine ...Orally, a meta-analysis of observational research has found that higher sodium intake is associated with an average increase in body mass index (BMI) of 1. 24 kg/m2 and an approximate 5 cm increase in waist circumference (98182). It has been hypothesized that the increase in BMI is related to an increased thirst, resulting in an increased intake of sugary beverages and/or consumption of foods that are high in salt and also high in fat and energy (98182). One large observational study has found that the highest sodium intake is not associated with overweight or obesity when compared to the lowest intake in adolescents aged 12-19 years when intake of energy and sugar-sweetened beverages are considered (106265). However, in children aged 6-11 years, usual sodium intake is positively associated with increased weight and central obesity independently of the intake of energy and/or sugar-sweetened beverages (106265).

Gastrointestinal ...In one case report, severe gastritis and a deep antral ulcer occurred in a patient who consumed 16 grams of sodium chloride in one sitting (25759). Chronic use of high to moderately high amounts of sodium chloride has been associated with an increased risk of gastric cancer (29405).

Musculoskeletal ...Observational research has found that low sodium levels can increase the risk for osteoporosis. One study has found that low plasma sodium levels are associated with an increased risk for osteoporosis. Low levels, which are typically caused by certain disease states or chronic medications, are associated with a more than 2-fold increased odds for osteoporosis and bone fractures (101260).
Conversely, in healthy males on forced bed rest, a high intake of sodium chloride (7.7 mEq/kg daily) seems to exacerbate disuse-induced bone and muscle loss (25760,25761).

Oncologic ...Population research has found that high or moderately high intake of sodium chloride is associated with an increased risk of gastric cancer when compared with low sodium chloride intake (29405). Other population research in patients with gastric cancer has found that a high intake of sodium is associated with an approximate 65% increased risk of gastric cancer mortality when compared with a low intake. When zinc intake is taken into consideration, the increased risk of mortality only occurred in those with low zinc intake, but the risk was increased to approximately 2-fold in this sub-population (109400).

Pulmonary/Respiratory ...In patients with hypertension, population research has found that sodium excretion is modestly and positively associated with having moderate or severe obstructive sleep apnea. This association was not found in normotensive patients (106262).

Renal ...Increased sodium intake has been associated with impaired kidney function in healthy adults. This effect seems to be independent of blood pressure. Observational research has found that a high salt intake over approximately 5 years is associated with a 29% increased risk of developing impaired kidney function when compared with a lower salt intake. In this study, high salt intake was about 2-fold higher than low salt intake (101261).

(Read more about SODIUM)

General ...Orally, xanthan gum can cause flatulence and abdominal distention (4916,4918). Topically, it has been reported to cause allergic reactions (100914).

Immunologic ...An itchy, burning dermatitis was reported in a 9-year old girl after application of a sunscreen product containing xanthan gum. Patch testing with the separate ingredients of the sunscreen identified xanthan gum as the reacting agent, and demonstrated a dose-dependent effect with 1% and 10% solutions (100914).

Pulmonary/Respiratory ...Occupational exposure in workers handling xanthan gum powder can cause flu-like symptoms and nose and throat irritation without acute or chronic loss of pulmonary function (4913).

(Read more about XANTHAN GUM)