ZuACV [Discontinued] by UMZU

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. 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. Although there has been interest in using oral apple cider vinegar for hyperlipidemia, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• 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).
• 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

• Breast cancer-related hot flashes. Oral chicory has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study of breast cancer survivors who use estrogen deprivation therapy shows that taking 5 mL of chicory and fumitory syrup 3 times daily for 4 weeks significantly decreases the frequency and severity of hot flashes when compared with placebo. Hot flash frequency and severity were both reduced by around 57% in the treatment group, as compared with a 10% reduction in the placebo group (110724). The use of a per-protocol analysis limits the validity of these findings. Additionally, it is unclear if these findings are due to chicory, fumitory, or the combination. Cancer. Although there has been interest in using oral chicory for the treatment or prevention of cancer, there is insufficient reliable information about the clinical effects of chicory for this purpose.
• Constipation. Although there has been interest in using oral chicory for constipation, there is insufficient reliable information about the clinical effects of chicory for this purpose.
• Diabetes. Although there has been interest in using oral chicory for diabetes, there is insufficient reliable information about the clinical effects of chicory for this purpose.
• Dyspepsia. Although there has been interest in using oral chicory for dyspepsia, there is insufficient reliable information about the clinical effects of chicory for this purpose.
• Hyperlipidemia. Although there has been interest in using oral chicory for hyperlipidemia, there is insufficient reliable information about the clinical effects of chicory for this purpose.
• Hypertension. Although there has been interest in using oral chicory for hypertension, there is insufficient reliable information about the clinical effects of chicory for this purpose.
• Neonatal jaundice. It is unclear if oral chicory solution is beneficial in neonates with jaundice. Details: A moderate-sized clinical study of nursing mothers shows that taking 50 mL of chicory 10% distillate every 12 hours for 3 days reduces bilirubin levels of breastfed neonates with jaundice by around 0.3 mg/dL when compared with placebo (110723). However, it is unlikely that these findings are clinically significant.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral chicory seed is beneficial in patients with NAFLD. Details: A small clinical trial in patients with NAFLD shows that taking chicory seed 9 grams infused in hot water daily for 12 weeks reduces body mass index (BMI) by 0.66 kg/m2 when compared with placebo. When combined with turmeric 3 grams daily, serum alkaline phosphatase was decreased. Although levels of other liver enzymes decreased when compared to baseline, changes were not significant when compared with placebo. Also, taking chicory seed did not affect plasma lipid levels (102350).
• Osteoarthritis. It is unclear if oral chicory root extract is beneficial in patients with osteoarthritis. Details: A small clinical study in patients with knee or hip osteoarthritis shows that taking chicory root extract 600 mg three times daily for 3 months does not improve pain, stiffness, or functional ability when compared with placebo (93647). However, this small study was likely underpowered to detect differences between groups. More evidence is needed to rate the effectiveness of chicory for these uses.

(Read more about CHICORY)

LIKELY EFFECTIVE

• Chromium deficiency. Oral or parenteral chromium is effective for the treatment and prevention of chromium deficiency. Details: Taking chromium orally is effective for preventing and treating symptoms of chromium deficiency, including hyperglycemia, glycosuria, sudden weight loss, peripheral neuropathy, and confusion (7135).

POSSIBLY EFFECTIVE

• Diabetes. Oral chromium seems to be modestly beneficial for improving glycemic control in diabetes, especially when used in doses greater than 200 mcg daily and in patients with poorly controlled diabetes. It is unclear if chromium helps to prevent the development of diabetes. Details: Epidemiological research has found that lower toenail chromium levels are associated with an increased risk of diabetes and cardiovascular disease (11908). In 2005, the US Food and Drug Administration (FDA) allowed a qualified health claim stating that chromium picolinate may reduce the risk of type 2 diabetes. However, the FDA has determined that any relationship between chromium picolinate and type 2 diabetes is highly uncertain and is based on limited scientific evidence (102362). Research on the use of chromium for the TREATMENT of type 2 diabetes is conflicting but seems to show modest benefit in some patients. Many small clinical studies show that taking chromium orally decreases fasting blood glucose, postprandial glucose, insulin, and glycated hemoglobin (HbA1C) levels, and increases insulin sensitivity (6867,7137,12390,15169,14440,42628,42638,95097,103745). However, other small clinical studies show that chromium is no better than placebo for improving glycemic indices in patients with diabetes (7060,14325,42679,42707,90059,103746,103749). Some of these studies may not have been adequately powered and some had a high risk of bias. Furthermore, these studies had high heterogeneity related to study population and size, chromium supplementation duration, formulation, and dose, and accepted standards of diabetes care. Multiple meta-analyses pooling results of these small clinical trials also show mixed results (90055,90063,95098,105026,110610). The most recent and comprehensive meta-analyses show that chromium picolinate lowers HbA1C by about 0.6%; while it is unclear if chromium yeast, chromium dinicocysteinate, or chromium with biotin or other natural ingredients are beneficial. Chromium seems to be most beneficial in doses of greater than 200 mcg taken for 12 weeks or longer, and in patients with poorly controlled diabetes with a baseline HbA1C of 8% or greater (90063,105026). There is also speculation that chromium might primarily benefit patients with low chromium levels; however, there has not been an analysis specifically evaluating this population (6867,7058,13725,14325,95098). Some research suggests that chromium might also modestly improve lipid levels in patients with type 2 diabetes (1934,6867,95098). A meta-analysis of randomized clinical trials including patients with type 2 diabetes shows that taking chromium 42-1000 mcg orally daily for 5-26 weeks decreases triglyceride levels by 7 mg/dL and increases high-density lipoprotein cholesterol levels by 2 mg/dL when compared with control. Taking chromium did not affect low-density lipoprotein cholesterol levels. However, the validity of these results is limited by high heterogeneity (110605). In addition, some meta-analyses have failed to demonstrate any effects of chromium on lipid levels (110610). A meta-analysis of randomized clinical trials including patients with type 2 diabetes shows that taking chromium 200-1000 mcg orally daily for 8-25 weeks lowers diastolic blood pressure by 2 mmHg, but not systolic blood pressure or body mass index, when compared with placebo (110607). Preliminary clinical research shows that chromium picolinate might improve metabolic parameters in patients with other forms of diabetes as well. This includes those with type 1 diabetes (1935), diabetes secondary to corticosteroid use (5039,42829), and gestational diabetes (42817).

POSSIBLY INEFFECTIVE

• Hypertension. Meta-analyses of small clinical trials suggest that oral chromium does not lower blood pressure by a clinically meaningful amount. Details: A meta-analysis of randomized clinical trials in adults with different metabolic disorders shows that taking chromium 42-1000 mcg orally daily for 12-24 weeks does not lower systolic or diastolic blood pressure when compared with placebo (110609). A meta-analysis of randomized clinical trials in adults with different chronic disorders shows that taking chromium 42-1000 mcg orally daily for 4-25 weeks lowers systolic and diastolic blood pressure by 3 mmHg and 1 mmHg, respectively, when compared with placebo. However, the validity of this meta-analysis is limited by high heterogeneity (110604). Another meta-analysis of randomized clinical trials including patients with type 2 diabetes shows that taking chromium 200-1000 mcg orally daily for 8-25 weeks lowers diastolic blood pressure by 2 mmHg, but not systolic blood pressure, when compared with placebo (110607). In addition, the validity of these results is limited by inclusion of patients with and without hypertension at baseline (110604,110607,110609).
• Impaired glucose tolerance (Prediabetes). Oral chromium does not seem to improve glycemic indices in patients with prediabetes. Details: Some clinical research shows that adults with impaired glucose tolerance do not have improved glycemic parameters or insulin sensitivity after taking chromium picolinate 500-1000 mcg daily for up to 6 months when compared with placebo (13053,42670). Likewise, a small clinical study in elderly patients with impaired glucose tolerance shows that chromium supplements do not improve glucose tolerance or triglyceride or cholesterol levels when compared with placebo (13722). Finally, a preliminary clinical study in overweight or obese adults with prediabetes shows that taking two capsules of a combination product containing chromium, cinnamon, and carnosine (Glycabiane, PiLeJe) daily for 4 months decreases fasting plasma glucose by approximately 4 mg/dL when compared with placebo, but does not improve fasting plasma insulin, measures of insulin sensitivity or resistance, or glycated hemoglobin (HbA1C) (94234). The small effect on fasting plasma glucose is clinically insignificant and may be due to the other ingredients in this product.
• Schizophrenia. Oral chromium does not seem to improve psychological measures in patients with schizophrenia. Details: Clinical research in patients with schizophrenia shows that taking chromium polynicotinate 400 mcg daily for 3 months does not affect weight or mental status when compared with placebo (42613).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Antiretroviral-induced insulin resistance. It is unclear if oral chromium is beneficial for preventing antiretroviral-induced insulin resistance. Details: Preliminary clinical research in HIV patients treated with highly active antiretroviral therapy (HAART) shows that taking chromium nicotinate 200 mcg or chromium picolinate 1000 mcg daily for 8-16 weeks may help decrease insulin resistance and increase glucose disposal when compared to baseline (42630,42662). The validity of this finding is limited by the lack of a control group.
• Athletic performance. It is unclear if chromium enhances athletic performance, although some research suggests that it may improve body composition when used in conjunction with exercise. Details: One large clinical study shows taking chromium 400 mcg daily, in conjunction with resistance training, can increase weight loss, body fat loss, and lean body mass when compared with placebo and resistance training (6868). However, other, very small clinical studies show that adding chromium picolinate or chromium chloride 177-400 mcg daily to a weight-training program does not improve body composition when compared with weight-training alone (6860,6861,6862,42747). These studies may not have been adequately powered to detect a difference in outcomes.
• Atypical depression. It is unclear if oral chromium is beneficial in patients with atypical depression. Details: Preliminary clinical research in patients with atypical depression shows that taking chromium picolinate 400 mcg daily for 2 weeks followed by 600 mcg daily for an additional 6 weeks improves response and remission rates when compared with placebo (10309). However, other clinical research shows that taking elemental chromium 400 mcg in the form of chromium picolinate daily for 2 weeks followed by 600 mcg daily for an additional 6 weeks does not improve most symptoms of atypical depression, although appetite and sexual drive may improve, when compared with placebo (42600).
• Beta blocker-induced dyslipidemia. It is unclear if oral chromium is beneficial in patients with dyslipidemia due to beta-blocker use. Details: One small clinical study in patients who take beta-blockers shows that taking glucose tolerance factor (GTF)-chromium 600 mcg daily for 2 months increases high-density lipoprotein (HDL) cholesterol levels by 16%, but does not affect other lipid parameters, when compared with placebo (5040).
• Binge eating disorder. It is unclear if oral chromium is beneficial in patients with binge eating disorder. Details: One small clinical study in overweight adults with binge eating disorder shows that taking chromium picolinate 600 or 1000 mcg by mouth daily for 6 months does not affect binge eating frequency, body weight, or depressive symptoms when compared with placebo (90057).
• Bipolar disorder. It is unclear if oral chromium is beneficial in patients with treatment-resistant bipolar disorder. Details: Preliminary clinical research in patients with treatment-resistant, rapid-cycling bipolar disorder shows that taking chromium chloride (Hypo-A Chrom, Hypo-A GmbH) 600-800 mcg daily for up to 2 years can decrease the frequency of affective episodes by approximately three episodes annually when compared to baseline (42618). The validity of this finding is limited by the lack of a control group.
• Cognitive impairment. It is unclear if oral chromium prevents cognitive impairment. Details: Some clinical research shows that taking chromium picolinate standardized to contain elemental chromium 1000 mcg daily for 12 weeks does not improve memory or depression in elderly patients with mild cognitive impairment when compared with placebo. However, results from neuroimaging scans suggest that chromium increases the activity of certain regions of the brain during memory tasks when compared with placebo (42666).
• Hyperlipidemia. Small clinical studies suggest that oral chromium may modestly reduce lipid levels in patients with hyperlipidemia. Details: One small clinical study in patients with atherosclerotic disease shows that taking chromium 250 mcg as chromium chloride daily for 7-16 months decreases triglycerides and increases high-density lipoprotein (HDL) cholesterol, but not other lipid parameters, when compared with placebo (7060). Other small clinical studies in adults with hyperlipidemia show that taking chromium picolinate 200 mcg daily for 6 weeks, chromium polynicotinate 200 mcg twice daily, or brewer's yeast containing 48 mcg elemental chromium daily for 6-8 weeks decrease total and low-density lipoprotein (LDL) cholesterol when compared to baseline (37178,42585,42710). The validity of this finding is limited by the lack of comparison with a control group. A meta-analysis of small heterogeneous clinical studies in patients mostly without hyperlipidemia shows that taking chromium orally does not affect lipid levels when compared with placebo (105029). A meta-analysis of randomized clinical trials including patients with type 2 diabetes shows that taking chromium 42-1000 mcg orally daily for 5-26 weeks modestly improves triglyceride and HDL cholesterol levels, but not LDL cholesterol levels, when compared with control. However, the validity of these results is limited by high heterogeneity and inclusion of patients with and without hyperlipidemia (110605). In addition, some meta-analyses have failed to demonstrate any effects of chromium on lipid levels in adults with diabetes (110610). Limited research has tested high-dose chromium in children. One small clinical study in children with hypercholesterolemia shows that taking chromium polynicotinate 400-600 mcg with glucomannan 1000-1500 mg twice daily for 8 weeks reduces total and LDL cholesterol when compared to baseline (90061). It is unclear if this effect is due to chromium, glucomannan, or the combination. Finally, chromium does not seem to reduce lipid levels in people without hyperlipidemia.
• Hypoglycemia. It is unclear if oral chromium helps to reverse or prevent hypoglycemia. Details: One very small clinical study in patients with reactive hypoglycemia shows that taking chromium chloride 200 mcg daily for 3 months increases blood glucose levels and improves insulin binding and hypoglycemic symptoms following an oral glucose load (6859). Another small clinical study in patients with symptomatic hypoglycemia shows that taking chromium yeast (Biochrome, Pharma-Nord) 125 mcg daily for 3 months improves symptoms, including chilliness, trembling, and disorientation, when compared with baseline (42711). The validity of this finding is limited by the lack of a control group.
• Metabolic syndrome. It is unclear if oral chromium is beneficial in patients with metabolic syndrome. Details: One small clinical study in patients with metabolic syndrome shows that taking a particular chromium picolinate product (Chromax, Nutrition 21) 500 mcg twice daily for 16 weeks does not affect weight, waist circumference, insulin sensitivity, glycated hemoglobin (HbA1C), or lipid levels when compared with placebo (42654).
• Myocardial infarction (MI). It is unclear if oral chromium helps to prevent MI. Details: Epidemiological research has found that low toenail chromium concentrations are associated with an increased risk of MI (13728). However, toenail chromium concentrations might not be a reliable predictor of body stores of chromium. There is also no reliable research showing that chromium supplements can prevent MI.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral chromium slows NAFLD progression. Details: One small clinical study in patients with NAFLD shows that taking chromium picolinate 200 mcg two times daily after meals for 12 weeks does not affect liver enzyme levels or body weight when compared with placebo (105027).
• Obesity. Although some research suggests that oral chromium may increase weight loss, this increase in weight loss is not likely to be considered clinically relevant. Details: Meta-analyses of clinical studies in overweight or obese adults show that taking chromium picolinate 200-1000 mcg daily for 12-16 weeks might result in a cumulative weight loss of about 0.5-1 kg when compared with placebo (90062,90065). However, this small reduction in weight is unlikely to be considered clinically significant. Furthermore, certain small clinical studies in healthy, overweight or obese adults and children show that taking oral chromium 200-1000 mcg daily for 6-24 weeks does not reduce weight when compared with control (6860,13727,17224,42680). Some of these studies may not have been adequately powered to detect a smaller effect. A meta-analysis of randomized clinical trials including patients with type 2 diabetes shows that taking chromium 200-1000 mcg orally daily for 8-25 weeks does not lower body mass index when compared with placebo. However, the validity of these results is limited by inclusion of patients with and without obesity at baseline (110607).
• Polycystic ovary syndrome (PCOS). It is unclear if oral chromium improves symptoms of PCOS. Details: One small clinical study in patients with PCOS shows that taking chromium picolinate 1000 mcg daily for 6 months along with diet and exercise counseling decreases body mass index and improves rates of ovulation and regular menstruation when compared with placebo (95094). Also, some clinical research shows that taking chromium picolinate (21st Century HealthCare, Inc. or Nature Made) 200 mcg daily orally for 8 weeks increases insulin sensitivity when compared with placebo (95095,98687). However, other preliminary clinical research shows that taking chromium picolinate 200 mcg daily for 4 months does not affect insulin sensitivity or improve ovulation rates (42603). Although chromium picolinate at doses of less than 1000 mcg might have very small effects on fasting glucose, these doses do not seem to have clinically beneficial effects on fasting glucose, pregnancy rate, or testosterone levels (95094,95095,98687). A lower dose of chromium has also been studied in combination with carnitine. One small clinical study in overweight adults with PCOS shows that taking chromium picolinate 200 mcg daily with carnitine 1000 mg daily for 12 weeks modestly reduces fasting blood glucose, insulin resistance, and body weight, and slightly increases insulin sensitivity, when compared with placebo (103747). However, it is unclear if this benefit is clinically significant. Additionally, it is unclear if these effects are due to chromium, carnitine, or the combination. Carnitine has demonstrated clinical benefit when used alone in PCOS.
• Turner syndrome. It is unclear if oral chromium is beneficial in patients with this condition. Details: A small clinical study shows that taking brewer's yeast 30 grams containing chromium 50 mcg daily for 8 weeks might improve abnormalities in glucose and lipid metabolism when compared with baseline in patients with Turner syndrome, a genetic disorder that has a high incidence of diabetes (13729). The validity of this finding is limited by the lack of a comparator group. More evidence is needed to rate chromium for these uses.

(Read more about CHROMIUM)

POSSIBLY EFFECTIVE

• Constipation. Most clinical research shows that oral inulin modestly improves stool frequency, but may not improve discomfort, in adults and children with constipation. Details: A meta-analysis of clinical research in adults with constipation shows that consuming inulin improves stool frequency by approximately 0.7 stools per week. It also seems to improve stool transit time, consistency, and hardness, but does not reduce pain or bloating (93718). Additional clinical research shows that taking a specific type of inulin (OraftiGR, BENEO GmbH) 12 grams daily in three divided doses for 4 weeks increases stool frequency by approximately one stool per week when compared with a maltodextrin control. Taking inulin also reduces the number of patients experiencing hard and lumpy stools by 13%, but does not improve symptoms of bloating, distension, physical discomfort, or gas (96850). In children aged 2-5 years, one small clinical study shows that taking a specific combination of two inulin products (Orafti P95 oligofructose and Orafti GR inulin, BENEO GmbH), 2 grams twice daily in a dairy liquid for 6 weeks, improves the softness of stools, but not pain with stooling or stool frequency, when compared with a maltodextrin control (96848). Research in older adults is conflicting. One small study shows that taking inulin 20-40 grams daily for 19 days increases the number of stools from 1-2 per week to 8-9 per week (10415). However, other preliminary clinical research in this population shows that taking a specific inulin supplement (Fibruline Instant, Cosucra Groupe Warcoing) 15 grams daily in yogurt or stewed fruit for 4 weeks does not improve bowel symptoms, stool frequency, or stool consistency (93724).
• Diabetes. Short-term use of oral inulin along with antidiabetes drugs may improve glycemic control in some patients with type 2 diabetes; however, the benefits of long-term use are unclear. Details: Two meta-analyses of clinical research in normal weight and obese patients with type 2 diabetes show that taking inulin 0.8-10 grams orally daily for 6-12 weeks reduces glycated hemoglobin (HbA1c) by 0.65% and fasting plasma glucose by 16 mg/dL when compared with control. Taking inulin also improved HOMA-IR, a measure of insulin resistance, when compared with control. Researchers did not evaluate the most effective dose of inulin; however, most studies used 8.4-10 grams daily (103198,105533). In females treated with metformin and glyburide, taking inulin 10 grams daily for 8 weeks reduces fasting blood glucose by 15 mg/dL and HbA1c by 1% when compared with placebo (93719). Population research in adults has also found that high dietary intake of inulin over 8 years of follow up is associated with a 6% lower risk of type 2 diabetes when compared with low dietary intake (110515). Inulin has also been studied in combination with other supplements. Preliminary clinical research in elderly patients with diabetes shows that drinking a milk powder product supplemented with inulin and resistant dextrin 30 grams before breakfast and 15 grams before dinner for 12 weeks decreases fasting plasma glucose by 17 mg/dL, HbA1c by 0.38%, postprandial glucose by 27 mg/dL, body weight by 0.8 kg, and systolic and diastolic blood pressure by 5 mmHg when compared with placebo (99843). Other clinical research in adults with type 2 diabetes shows that taking a specific combination product (Orafti Synergy1, BENEO GmbH), containing 50% inulin and 50% fructo-oligosaccharides, 8 grams orally twice daily for 6 weeks does not reduce body weight or caloric intake or increase satiety scores when compared with placebo (107934).
• Obesity. Oral inulin might modestly improve short-term weight loss. Additional research is needed to determine the long-term effects of inulin on weight loss and weight maintenance in overweight or obese individuals. Details: Some clinical research in overweight and obese females with diabetes shows that taking inulin 10 grams daily for 8 weeks results in weight loss of 2.6 kg, compared with no weight loss in those taking placebo (93719). Preliminary clinical research in overweight or obese patients with prediabetes shows that taking a specific brand of inulin (Orafti Synergy 1, BENEO GmbH) 30 grams orally daily for 6 weeks reduces body weight by 0.4 kg, compared with a 0.4 kg increase in those in the control group (93721). Preliminary clinical research in adults with obesity shows that taking inulin 16 grams orally daily for 3 months moderately reduces body weight and body mass index (BMI) when compared with placebo. However, these effects were most prominent in subjects that also increased physical activity (110514). Additional preliminary clinical research in adults with overweight shows that adding 18 grams of inulin powder to green tea daily increases weight loss when compared with green tea alone. Over six weeks, individuals taking inulin lost 2 kg, compared with no weight loss in those taking green tea. Weight loss was maintained for at least 2 weeks (93726). Clinical trials in children show conflicting results. In children aged 7-12 years, a small clinical study shows that taking a specific oligofructose-enriched inulin product (Orafti Synergy1, BENEO GmbH) 8 grams orally in water before one meal daily for 16 weeks decreases weight gain by 2.4-fold and attenuates an increase in BMI when compared with placebo (96847). However, other preliminary clinical research in children with obesity aged 7-15 years shows that taking inulin extract 13 grams orally daily for 6 months does not reduce body weight or BMI when compared with placebo (110598). However, other clinical research shows that taking inulin orally in combination with other ingredients might not improve weight loss. Combining inulin, chromium picolinate, capsicum, L-phenylalanine, and other nutrients with caloric reduction and exercise doesn't seem to reduce weight in moderately obese patients when compared to caloric reduction and exercise alone (7607). Another preliminary clinical trial shows that taking inulin 10 grams with maltodextrin 10 grams daily for 12 weeks does not reduce body weight or improve body composition when compared with placebo in adults with overweight or obesity following a calorie-restricted diet (103202). Preliminary clinical research in adults with obesity also shows that consuming a seafood-based dietary product fortified with inulin 1.7 grams, fish oil 370 mg (containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and bifidobacterium animalis daily for 12 weeks does not lower body weight, waist circumference, abdominal fat, serum cholesterol levels, or blood pressure when compared with placebo. However, consuming the product modestly improved some markers of insulin resistance (110600).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alcohol use disorder. It is unclear if oral inulin is beneficial in patients with alcohol use disorder. Details: Preliminary clinical research in adults with alcohol use disorder who were recently admitted to the hospital shows that taking a specific inulin product (Fibruline, Cosucra) 4-16 grams orally daily for 17 days does not improve liver function tests when compared with placebo. Some liver function tests were also worse in those treated with inulin (110601).
• Antibiotic-associated diarrhea. Oral inulin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children aged 6 months to 14 years receiving antibiotics for common infections shows that taking a combination of inulin and fructo-oligosaccharides, up to 5 grams daily depending on age, does not reduce the rate of antibiotic-associated diarrhea (93720).
• Celiac disease. Small clinical studies suggest that patients with celiac disease who take oral inulin may have a lower risk of vitamin and mineral deficiency. Details: Preliminary clinical research in a small number of children and adolescents with vitamin and mineral malabsorption due to celiac disease shows that taking a specific oligofructose-enriched inulin product (Orafti Synergy 1, BENEO GmbH) 10 grams daily for 3 months improves the absorption of vitamin D, vitamin E, and iron, but not vitamin A (99841,99842). Levels of 25-hydroxy vitamin D and vitamin E increased by 42% and 19%, respectively, compared with no significant improvements in those taking placebo (99842). Although taking inulin did not improve serum ferritin levels, it did decrease serum hepcidin concentrations by 61% when compared with baseline, while no significant improvement was reported with placebo. Hepcidin is a regulator of iron homeostasis, and increased levels are associated with iron-deficiency anemia (99841).
• Child growth. Oral inulin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in healthy, exclusively formula-fed, infants less than 4 months of age shows that supplementing formula with 0.8 grams/dL of a specific combination product (Orafti Synergy1, Beneo-Orafti) containing 50% inulin and 50% fructo-oligosaccharide until 12 months of age does not improve markers of child growth, including body weight, length, and head circumference, when compared with placebo. The combination product was associated with a reduced duration of fever during infectious episodes, but not with a reduction in the number of infections. It is unclear if any potential effects are due to inulin, fructo-oligosaccharide, or the combination (107937).
• Chronic kidney disease (CKD). It is unclear if oral inulin is beneficial in patients with CKD. Details: In adults with CKD, adding inulin 19 grams daily for 6 months to a low-protein diet reduces serum insulin, fasting plasma glucose, total serum cholesterol, triglycerides, and markers of systemic inflammation, while increasing serum high density lipoprotein (HDL) cholesterol, when compared with baseline (105534). However, it is unclear if similar changes occur with a low-protein diet alone, or if the rate of progression of CKD is reduced. Population research in adults has found that high dietary intake of inulin over 8 years of follow up is not associated with a lower risk of CKD when compared with low dietary intake (110515).
• Hypercholesterolemia. It is unclear if oral inulin reduces cholesterol levels in patients with hypercholesterolemia. Details: Research in patients with hypercholesterolemia has shown mixed results, with some studies showing a small decrease and others showing no improvement in serum cholesterol levels (7604,8450,10412,10413,96849). A typical dose of inulin used is 6 grams orally three times daily for up to 6 weeks (10412). A meta-analysis of healthy, dyslipidemic, overweight or diabetic patients shows that inulin reduces levels of low-density lipoprotein (LDL) cholesterol by approximately 5% (96849). Another meta-analysis of randomized clinical trials in the same population shows that taking inulin 1.5-30 grams daily for 2-12 weeks reduces LDL cholesterol levels by 7 mg/dL and increases high-density lipoprotein cholesterol levels by 2 mg/mL when compared with control. However, this meta-analysis also included data from patients treated with fructo-oligosaccharides instead of inulin (107940).
• Hypertension. It is unclear if oral inulin is beneficial in patients with hypertension. Details: Population research in adults has found that high dietary intake of inulin over 8 years of follow up is associated with a 21% lower risk of hypertension when compared with low dietary intake (110515).
• Hypertriglyceridemia. It is unclear if oral inulin is beneficial in patients with hypertriglyceridemia. Details: A meta-analysis of clinical trials in normal and moderately hyperlipidemic patients suggests that taking inulin-type fructans at an approximate average dose of 14 grams daily reduces triglyceride levels by about 15 mg/dL when compared with control (93737). However, other research, including a meta-analysis of healthy, dyslipidemic, overweight or diabetic patients shows that taking inulin 1.5-30 grams daily for 2-12 weeks does not reduce triglyceride levels when compared with control. However, these negative studies are limited by small sample sizes and inclusion of data from patients treated with fructo-oligosaccharides instead of inulin (7604,107940).
• Impaired glucose tolerance (prediabetes). Several small clinical studies suggest that oral inulin is not beneficial in patients with prediabetes. Details: Preliminary clinical research in adults with prediabetes shows that taking inulin 15 grams orally daily for 24 weeks does not improve fasting blood glucose, glycated hemoglobin (HbA1c), or lipid levels when compared with placebo. However, taking inulin modestly improved markers of insulin resistance (107938). Two other, small, clinical trials show that taking specific inulin products (Orafti Synergy 1, BENEO GmbH or Frutafit IQ, Sensus American) 10-30 grams daily for 6 weeks does not improve blood glucose, insulin resistance, glucose homeostasis, or insulin sensitivity when compared with placebo (93721,107936). However, these studies may have been inadequately powered to detect a difference between groups.
• Iron deficiency anemia. Oral inulin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in young adult females with iron deficiency anemia shows that taking inulin 963 mg/kg and iron supplementation orally daily for 3 months modestly improves serum hemoglobin, hematocrit, and iron levels when compared with a control group consuming iron-fortified flour (110599).
• Menopausal symptoms. It is unclear if oral inulin is beneficial in patients with hypertriglyceridemia. Details: Preliminary clinical research in adults experiencing menopause shows that consuming yogurt enriched with a specific inulin (Frutafit TEX, Sensus Company) 1.5% daily for 6 weeks moderately improves menopausal symptom scores, including depression, anxiety, and vasomotor symptoms, when compared with yogurt alone (107659).
• Nonalcoholic fatty liver disease (NAFLD). Taking oral inulin alone does not seem to improve liver transaminase levels in patients with NAFLD. Details: Preliminary clinical research in patients with NAFLD shows that taking metronidazole 400 mg twice daily for one week plus inulin 4 grams twice daily for 12 weeks reduces levels of alanine aminotransferase and aspartate aminotransferase when compared with placebo. However, when inulin is taken without metronidazole, these measures are not improved (103200).
• Polycystic ovary syndrome (PCOS). It is unclear if oral inulin is beneficial in patients with PCOS. Details: Preliminary clinical research in overweight or obese females with PCOS shows that taking specific products containing inulin (FrutaFit TEX, Sensus American) or inulin and fructo-oligosaccharides (FrutaFit IQ, Sensus American) 10 grams orally once daily for 12 weeks does not reduce systolic or diastolic blood pressure when compared with placebo. However, the validity of this study is limited by the inclusion of subjects with and without hypertension at baseline (107941). More evidence is needed to rate inulin for these uses.

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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)

LIKELY SAFE ...when consumed in amounts commonly found in food. Chicory and chicory extract have Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used orally in medicinal amounts, short-term. Chicory root extract has been used with apparent safety at doses of 600 mg three times daily for one month (93647). Chicory seed has been used with apparent safety as a hot water infusion of 4.5 grams twice daily for 12 weeks (102350). There is insufficient reliable information available about the safety of chicory when used orally, long-term, or when used topically.

PREGNANCY: POSSIBLY UNSAFE
when used orally in excessive amounts. Chicory may induce menstruation or miscarriage (19).

LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Chromium has been safely used in doses up to 1000 mcg daily for up to 6 months (1934,5039,5040,6858,6859,6860,6861,6862,6867,6868)(7135,7137,10309,13053,14325,14440,17224,90057,90061)(90063,94234,95095,95096,95097,98687); however, most of these studies have used chromium doses in a range of 150-600 mcg. The Food and Drug Administration (FDA) and Institute of Medicine (IOM) evaluations of the safety of chromium suggest that it is safe when used in doses of 200 mcg daily for up to 6 months (13241,13242).

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, long-term. Chromium has been safely used in a small number of studies at doses of 200-1000 mcg daily for up to 2 years (7060,7135,42618,42628,42666,110605,110607,110609). However, the Food and Drug Administration (FDA) and Institute of Medicine (IOM) evaluations of the safety of chromium suggest that it is safe when used in doses of 200 mcg daily for up to 6 months (13241,13242).

CHILDREN: LIKELY SAFE
when used orally and appropriately in amounts not exceeding the daily adequate intake (AI) levels by age: 0-6 months, 0. 2 mcg; 7-12 months, 5.5 mcg; 1-3 years, 11 mcg; 4-8 years, 15 mcg; males 9-13 years, 25 mcg; males 14-18 years, 35 mcg; females 9-13 years, 21 mcg; females 14-18 years, 24 mcg (7135). POSSIBLY SAFE...when used orally and appropriately in amounts exceeding AI levels. Chromium 400 mcg daily has been used safely for up to 6 weeks (42680).

PREGNANCY: LIKELY SAFE
when used orally and appropriately in amounts not exceeding adequate intake (AI) levels. The AI for pregnancy is 28 mcg daily for those 14-18 years of age and 30 mcg daily for those 19-50 years of age (7135).

PREGNANCY: POSSIBLY SAFE
when used orally in amounts exceeding the adequate intake (AI) levels. There is some evidence that patients with gestational diabetes can safely use chromium in doses of 4-8 mcg/kg (1953); however, patients should not take chromium supplements during pregnancy without medical supervision.

LACTATION: LIKELY SAFE
when used orally and appropriately in amounts not exceeding adequate intake (AI) levels. The AI for lactation is 44 mcg daily for those 14-18 years of age and 45 mcg daily for those 19-50 years of age (7135). Chromium supplements do not seem to increase normal chromium concentration in human breast milk (1937). There is insufficient reliable information available about the safety of chromium when used in higher amounts while breast-feeding.

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LIKELY SAFE ...when used orally in amounts commonly found in foods. Inulin has Generally Recognized As Safe status (GRAS) in the US (93728).

POSSIBLY SAFE ...when used orally and appropriately in supplemental doses, short-term. Doses of 8-18 grams daily have been used safely for up to 24 weeks (7604,7605,7606,7607,8451,93716,93719,93726,103200,107936,107935,107938). Also, 20 grams daily has been used with apparent safety for up to 3 weeks (96836,96850). There is insufficient reliable information available about the safety of inulin when used long-term.

CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods. Inulin has Generally Recognized As Safe status (GRAS) in the US (93728).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately in supplemental doses, short-term. Clinical studies have used doses of 3-6 grams daily for 10 days in children 3-6 years of age and 5-13 grams daily for up to 6 months in children 7-15 years of age with apparent safety (96847,110598,110602). ...when used in infant formula. A formula containing chicory fructans (Orafti Synergy1, BENEO GmbH), approximately 50% of which were inulin, has been used with apparent safety in infants for 8-12 months (93717,107937).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (93728). There is insufficient reliable information available about using inulin in medicinal amounts during pregnancy or lactation; avoid use.

(Read more about INULIN)

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).

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, chicory might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Animal and in vitro research shows that chicory extracts have antidiabetic effects (93650,108543).

(Read more about CHICORY)

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = A Theoretically, chromium may have additive effects with antidiabetic agents and increase the risk of hypoglycemia.  Details Some research shows that taking chromium might lower blood glucose levels, especially in patients with poorly controlled type 2 diabetes (7137,14440,15169,94234,95097,95098,98687).

ASPIRIN Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Possible •  Level of Evidence = D Theoretically, aspirin might increase chromium absorption.  Details Animal research suggests that aspirin may increase chromium absorption and chromium levels in the blood (21055).

INSULIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use of chromium and insulin might increase the risk of hypoglycemia.  Details In clinical research, chromium has been shown to increase insulin sensitivity (1952,14440,95095),

LEVOTHYROXINE (Synthroid, others) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Chromium might bind levothyroxine in the intestinal tract and decrease levothyroxine absorption.  Details Clinical research in healthy volunteers shows that taking chromium picolinate 1000 mcg with levothyroxine 1 mg decreases serum levels of levothyroxine by 17% when compared to taking levothyroxine alone (16012). Advise patients to take levothyroxine at least 30 minutes before or 3-4 hours after taking chromium.

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D NSAIDs might increase chromium levels in the body.  Details Drugs that are prostaglandin inhibitors, such as NSAIDs, seem to increase chromium absorption and retention (7135).

(Read more about CHROMIUM)

ANTIDIABETES DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, inulin might increase the risk of hypoglycemia with antidiabetes drugs.  Details Some clinical research shows that inulin improves glycemic control in patients with diabetes; however, it is unclear if it has hypoglycemic effects (93719,99843,103198).

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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, chicory seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, belching, bloating, and flatulence.

Dermatologic ...Occupational exposure to chicory may cause skin rash, contact dermatitis, or generalized pruritus (41609,93649). The sesquiterpene lactones of the plant may be the allergens (41609). Chicory may cause an allergic reaction in individuals sensitive to the Asterceae/Compositae family (25416). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Gastrointestinal ...Orally, fructo-oligosaccharides, such as those extracted from chicory, can cause flatulence, belching, abdominal pains, intestinal sounds and bloating, which occur commonly, but are mild at doses of 10 grams daily (740,745,750,8509,93716).

Immunologic ...Occupational exposure to chicory may cause allergic reactions. Dyspnea and anaphylaxis have also been reported in a patient with regular occupational exposure to chicory. This patient also experienced contact dermatitis and generalized pruritus (93649).

Pulmonary/Respiratory ...Occupational exposure to chicory may cause asthma and rhinoconjunctivitis (41617,93648). Dyspnea and anaphylaxis have also been reported in a patient with regular occupational exposure to chicory. This patient also experienced contact dermatitis and generalized pruritus (93649).

(Read more about CHICORY)

General ...Orally, chromium is generally well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal irritation, headaches, insomnia, irritability, mood changes.
Serious Adverse Effects (Rare):
Orally: Rare cases of kidney and liver damage, rhabdomyolysis, and thrombocytopenia have been reported.

Dermatologic ...Orally, chromium-containing supplements may cause acute generalized exanthematous pustulosis (42561), skin rashes (42679), and urticaria (17224). Also, chromium picolinate or chromium chloride may cause systemic contact dermatitis when taken orally, especially in patients with contact allergy to chromium (6624,90058). In one clinical study, a patient taking chromium nicotinate 50 mcg daily reported itchy palms that improved after the intervention was discontinued. It is unclear of this effect was due to the chromium or another factor (95096).
Topically, hexavalent chromium, which can be present in some cement, leather products, or contaminated soil, may cause allergic contact dermatitis (42645,42789,90060,90064,110606).
A case of lichen planus has been reported for a patient following long-term occupational exposure to chromium (42688).

Endocrine ...Orally, cases of hypoglycemia have been reported for patients taking chromium picolinate 200-1000 mcg daily alone or 200-300 mcg two or three times weekly in combination with insulin (42672,42783). Chromium picolinate has also been associated with weight gain in young females who do not exercise and in those following a weight-lifting program (1938).

Gastrointestinal ...Orally, chromium in the form of chromium picolinate, chromium polynicotinate, chromium-containing brewer's yeast, or chromium-containing milk powder may cause nausea, vomiting, diarrhea, decreased appetite, constipation, flatulence, or gastrointestinal upset (14325,42594,42607,42622,42643,42679).
Long-term exposure to heavy metals, including chromium, has been associated with increased risk of gallbladder disease and cancer (42682,42704).

Genitourinary ...Orally, chromium polynicotinate has been associated with disrupted menstrual cycles in patients taking the supplement to prevent weight gain during smoking cessation (42643).

Hematologic ...Anemia, hemolysis, and thrombocytopenia were reported in a 33 year-old female taking chromium picolinate 1200-2400 mcg daily for 4-5 months (554). The patient received supportive care, blood product transfusions, and hemodialysis and was stabilized and discharged a few days later. Lab values were normal at a one-year follow-up.

Hepatic ...Liver damage has been reported for a 33-year-old female taking chromium picolinate 1200 mcg daily for 4-5 months (554). Also, acute hepatitis has been reported in a patient taking chromium polynicotinate 200 mcg daily for 5 months (9141). Symptoms resolved when the product was discontinued. Two cases of hepatotoxicity have been reported in patients who took a specific combination product (Hydroxycut), which also contained chromium polynicotinate in addition to several herbs (13037).

Musculoskeletal ...Acute rhabdomyolysis has been reported for a previously healthy 24-year-old female who ingested chromium picolinate 1200 mcg over a 48-hour time period (42786). Also, chromium polynicotinate has been associated with leg pain and paresthesia in patients taking the supplement to prevent weight gain during smoking cessation (42643).

Neurologic/CNS ...Orally, chromium picolinate may cause headache, paresthesia, insomnia, dizziness, and vertigo (6860,10309,14325,42594). Vague cognitive symptoms, slowed thought processes, and difficulty driving occurred on three separate occasions in a healthy 35-year-old male after oral intake of chromium picolinate 200-400 mcg (42751). Transient increases in dreaming have been reported in three patients with dysthymia treated with chromium picolinate in combination with sertraline (2659). A specific combination product (Hydroxycut) containing chromium, caffeine, and ephedra has been associated with seizures (10307). But the most likely causative agent in this case is ephedra.

Psychiatric ...Orally, chromium picolinate has been associated with irritability and mood changes in patients taking the supplement to lose weight, while chromium polynicotinate has been associated with agitation and mood changes in patients taking the supplement to prevent weight gain during smoking cessation (6860,42643).

Renal ...Orally, chromium picolinate has been associated with at least one report of chronic interstitial nephritis and two reports of acute tubular necrosis (554,1951,14312). Laboratory evidence suggests that chromium does not cause kidney tissue damage even after long-term, high-dose exposure (7135); however, patient- or product-specific factors could potentially increase the risk of chromium-related kidney damage. More evidence is needed to determine what role, if any, chromium has in potentially causing kidney damage.
Intravenously, chromium is associated with decreased glomerular filtration rate (GFR) in children who receive long-term chromium-containing total parenteral nutrition - TPN (11787). Topically, burns caused by chromic acid, a hexavalent form of chromium, have been associated with acute chromium poisoning with acute renal failure (42699). Early excision of affected skin and dialysis are performed to prevent systemic toxicity.

Other ...Another form of chromium, called hexavalent chromium, is unsafe. This type of chromium is a by-product of some manufacturing processes. Chronic exposure can cause liver, kidney, or cardiac failure, pulmonary complications, anemia, and hemolysis (9141,11786,42572,42573,42699). Occupational inhalation of hexavalent chromium can cause ulceration of the nasal mucosa and perforation of the nasal septum, and has been associated with pneumoconiosis, allergic asthma, cough, shortness of breath, wheezing, and increased susceptibility to respiratory tract cancer and even stomach and germ cell cancers (42572,42573,42601,42610,42636,42667,42648,42601,42788,90056,90066). Although rare, cases of interstitial pneumonia associated with chromium inhalation have been reported. Symptoms resolved with corticosteroid treatment (42614).

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General ...Orally, inulin is well tolerated.
Most Common Adverse Effects:
Orally: Bloating, constipation, diarrhea, flatulence, and gastrointestinal cramps.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis has occurred following consumption of foods high in inulin.

Gastrointestinal ...Orally, inulin may cause flatulence, bloating, diarrhea, constipation, and gastrointestinal cramps, especially at doses over 30 grams (7604,8450,8509,93716,93721,93724,96836,96850,96851,99843)(107936,107940,107941,110602).

Immunologic ...Severe allergic reactions to inulin-containing foods have been reported. There is one report of anaphylaxis following consumption of foods with a high concentration of inulin including salsify, artichoke leaves, and margarine (7608).

(Read more about INULIN)