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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there has been interest in using topical apple cider vinegar for acne, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Athletic performance. It is unclear if oral apple cider vinegar is beneficial for improving endurance during exercise. Details: Preliminary clinical research in a small number of healthy male athletes shows that drinking apple cider vinegar 500 mL one-hour prior to an endurance cycling test does not improve endurance capacity, as measured by respiratory exchange rate, heart rate, or blood levels of ammonia, glucose, or lactate, when compared with a commercial sports drink (103225). It is unknown if apple cider vinegar would improve endurance when compared with a placebo control.
• Atopic dermatitis (eczema). Although there has been interest in using topical apple cider vinegar for eczema, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Cognitive function. Although there has been interest in using oral apple cider vinegar to improve cognitive function, there is insufficient reliable information about the clinical effects of apple cider vinegar for this use.
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral apple cider vinegar for COVID-19, there is insufficient reliable information about the clinical effects of apple cider vinegar for this use.
• Dandruff. Although there has been interest in using topical apple cider vinegar for dandruff, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Dental plaque. It is unclear if topical apple cider vinegar prevents the accumulation of dental plaque. Details: A small clinical study in children aged 3-6 years with cerebral palsy shows that applying apple cider vinegar 5% to their teeth daily for 6 months reduces the accumulation of dental plaque when compared with manual tooth brushing without dental paste (111228). However, the validity of these findings is limited by a lack of blinding and poor study methodology.
• Depression. Although there has been interest in using oral apple cider vinegar for depression, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Diabetes. It is unclear if oral apple cider vinegar is beneficial for improving glucose control in patients with type 2 diabetes; evidence is conflicting. Details: Two meta-analyses of mainly lower-quality clinical trials in a variety of populations (i.e., healthy, overweight, or obese individuals or those with type 2 diabetes) show that taking apple cider vinegar daily for up to 12 weeks reduces fasting blood glucose (FBG) levels by about 8-21 mg/dL, glycated hemoglobin (HbA1c) by 0.5%-0.9%, and total cholesterol by 6-7 mg/dL when compared with control (e.g., water, another beverage, no beverage, or restricted calorie diet). There was no effect on levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, insulin, or on measures of insulin resistance. However, in sub-group analyses limited to patients with type 2 diabetes, the effect of apple cider vinegar on FBG or HbA1c levels is conflicting (106284,112355). Of note, both meta-analyses include studies with heterogeneous populations, varied dosages, and different durations that limit the interpretation of these pooled results. Small clinical studies show varying results. One small open-label clinical study conducted in Iran in adults with type 2 diabetes shows that taking apple cider vinegar 30 mL daily for 8 weeks reduces HbA1c by about 1.4% but does not impact fasting blood glucose when compared with control (113626). Notably, baseline HbA1c was about 9% in the apple cider vinegar group versus about 8% in the control group. It is unclear if modifications to antidiabetes medications were allowed during study enrollment. Additionally, a very small clinical study shows that taking apple cider vinegar 20 grams with a meal increases postprandial insulin sensitivity and reduces postprandial flux in insulin levels in patients with insulin resistance, but not those with type 2 diabetes, when compared with placebo (17614). Additionally, a very small clinical study shows that taking apple cider vinegar 20 grams with a meal increases postprandial insulin sensitivity and reduces postprandial flux in insulin levels in patients with insulin resistance, but not those with type 2 diabetes, when compared with placebo (17614). It is unclear if the formulation of apple cider vinegar alters its effects. One small crossover study in healthy adults found a modestly greater reduction in postprandial glucose with the use of liquid apple cider vinegar (providing 1.25 grams acetic acid) when compared with apple cider vinegar whole tablets or crushed tablets (providing 1.5 grams acetic acid) or water alone (106285). Larger studies are needed to confirm this finding.
• Dyspepsia. Although there has been interest in using oral apple cider vinegar for dyspepsia, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Gastroparesis. It is unclear if oral apple cider vinegar is beneficial for gastroparesis. Details: A very small clinical study shows that taking apple cider vinegar 30 mL daily worsens the gastric emptying rate in patients with type 1 diabetes and gastroparesis when compared with drinking water (17609).
• Gingivitis. It is unclear if topical apple cider vinegar prevents the development of gingivitis. Details: A small clinical study in children aged 3-6 years with cerebral palsy shows that applying apple cider vinegar 5% to the teeth daily for 6 months reduces gingivitis scores when compared to baseline, with results comparable to manual tooth brushing without dental paste at the end of the study period (111228). However, the validity of these findings is limited by a lack of blinding and poor methodology.
• Herpes zoster (shingles). Although there has been interest in using topical apple cider vinegar for shingles, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Hyperlipidemia. It is unclear whether oral apple cider vinegar is beneficial for hyperlipidemia. Details: A small open-label clinical study conducted in Iran in adults with type 2 diabetes shows that taking apple cider vinegar 30 mL daily for 8 weeks reduces low-density lipoprotein (LDL) cholesterol and total cholesterol but does not impact high-density lipoprotein (HDL) cholesterol or triglycerides when compared with control (113626).
• Impaired glucose tolerance (prediabetes). Although there has been interest in using oral apple cider vinegar for prediabetes, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Insect bite. Although there has been interest in using topical apple cider vinegar for insect bites, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Intestinal parasite infection. Although there has been interest in using oral apple cider vinegar for intestinal parasite infections, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Kidney stones (nephrolithiasis). It is unclear if oral apple cider vinegar reduces the risk for kidney stones. Details: Some population research suggests that the consumption of fermented vinegar can reduce the risk for kidney stones (97311). However, there is currently no clinical evidence confirming this association, or any studies specifically evaluating the use of apple cider vinegar for this purpose.
• Leg cramps. Although there has been interest in using oral apple cider vinegar for leg cramps, there is insufficient reliable information about the clinical effects of apple cider vinegar for this condition.
• Obesity. It is unclear if oral apple cider vinegar is beneficial for obesity. Details: A small clinical study in adults with overweight and obesity 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). Additionally, a small clinical study conducted in Lebanon in adolescents and young adults with overweight and obesity shows that taking 5, 10, or 15 mL of apple cider vinegar diluted in water every morning for 12 weeks modestly reduces weight and BMI when compared with placebo, with the greatest reduction observed with the 15 mL dose. Taking apple cider vinegar also modestly reduced fasting blood glucose, triglycerides, and serum cholesterol levels when compared with placebo(115305). Another small open-label clinical study conducted in Iran in adults with type 2 diabetes shows that taking apple cider vinegar 30 mL daily for 8 weeks reduces BMI and waist circumference but does not change waist-to-hip ratio when compared with control (113626). Overall, the validity of these results is limited by study size and generalizability.
• 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)

POSSIBLY EFFECTIVE

• Atopic dermatitis (eczema). In infants at risk for atopy, providing syrup or formula containing GOS along with probiotics or fructo-oligosaccharides may reduce the risk of developing atopic dermatitis. Details: One large clinical trial in infants at high risk for allergies shows that feeding 20 drops of syrup containing GOS 0.8 grams, in combination with one opened capsule of probiotic bacteria, daily for 6 months reduces the incidence of dermatitis and atopic dermatitis by the age of 2 years when compared with placebo (26707). It is unclear if these findings are due to GOS, probiotics, or the combination, especially since mothers in the treatment group also took probiotics for 2-4 weeks before delivery. Also, a small clinical trial in newborns at risk for atopic disease shows that feeding a formula containing a combination of GOS and fructo-oligosaccharides 8 grams/L as often as necessary for 6 months reduces the risk, but not severity, of developing atopic dermatitis when compared with placebo formula (26708). At 2 years of age, the infants given this formula were half as likely to have developed atopic dermatitis (99223). However, in one study in healthy formula-fed infants, formula containing 4 grams/L of GOS and polydextrose (1:1 ratio) given as often as necessary for approximately 4 months increased the potential of developing atopic dermatitis as an adverse effect by up to 11% when compared with control formula (26709).
• Colic. Providing formula containing GOS and other ingredients may reduce the duration or frequency of crying episodes in infants with colic. Details: One clinical trial in infants with colic shows that feeding a formula containing 8 grams/L of a prebiotic mixture of GOS 90% and fructo-oligosaccharides 10% as often as necessary for 14 days reduces the number of colic episodes when compared with a control formula plus simethicone 6 mg/kg twice daily (26710). Another clinical trial in healthy infants 14-35 days of age shows that feeding a cow's milk-based formula containing 4 grams/L of a prebiotic blend of GOS and polydextrose (1:1 ratio) until around 4 months of age leads to faster normalization of daytime sleep patterns when compared with cow's milk-based formula alone. Episodes of crying were also shorter after 2 months, but not 4 months, of supplementation (106527). It is unclear if the findings from this study in healthy infants can be generalized to those with colic.
• Lactose intolerance. Oral GOS may improve some symptoms of lactose intolerance and allow for increased consumption of lactose-containing products, even after discontinuing GOS. Details: Although a small clinical study found no effect with the use of GOS (99224), one large clinical study in patients with lactose intolerance shows that taking GOS titrated up to 7.5-10 grams twice daily for 30 days improves overall symptoms of lactose intolerance, and in particular cramping and bloating, when compared with placebo (106526). Patients in these studies were asked to avoid lactose-containing products during the treatment period, so the effect of GOS on symptoms in patients actively consuming lactose products is unclear. After the study period, patients were asked to reintroduce lactose products into their diets. Those that had been taking GOS in both studies reported increased milk intake and fewer symptoms when compared with those previously treated with placebo, suggesting that the effects of GOS continue after discontinuation (99224,106526).

POSSIBLY INEFFECTIVE

• Allergic rhinitis (hay fever). Supplementation with oral GOS during the first 6 months of life may not prevent the development of allergic rhinitis in infants at risk for allergies. Details: One large clinical trial in infants at risk for allergies shows that feeding 20 drops of syrup containing GOS 0.8 grams, in combination with one opened capsule of probiotic bacteria, daily for 6 months does not reduce the risk of developing allergic rhinitis by the age of 2 years when compared with placebo (26707).
• Food allergies. Supplementation with oral GOS during the first 6-12 months of life may not prevent the development of food allergies at 1 or 2 years of age. Details: One large clinical trial in infants at risk for allergies shows that feeding 20 drops of syrup containing GOS 0.8 grams, in combination with one opened capsule of probiotic bacteria, daily for 6 months does not reduce the risk of developing food allergies by the age of 2 years when compared with placebo (26707). Another large clinical study in healthy, full-term infants shows that feeding a formula containing GOS 4.4-5 grams/L from 8 weeks of age until 12 months of age does not reduce the incidence of allergic sensitization to foods, based on skin prick testing, when compared with placebo (99218).
• Upper respiratory tract infection (URTI). Large studies suggest that oral GOS do not prevent the development of URTIs in healthy infants or young adults. It is unclear if GOS are beneficial for the prevention of URTIs in premature infants. Details: A large clinical study in healthy, term infants shows that feeding a formula containing GOS 4.4-5 grams/L from before 8 weeks of age until 12 months of age does not reduce the incidence of URTIs (99218). Also, a large clinical trial in healthy university students going through exam-related stress shows that taking GOS (Purimmune, GTC Nutrition) 2.5 or 5 grams daily for 8 weeks does not reduce the total number of cold or flu symptoms when compared with placebo (99221). GOS, in combination with polydextrose, has been evaluated in premature infants. A small clinical trial shows that feeding a 1:1 combination of these at a dose of 600-1200 mg daily during the first 60 days of life reduces the incidence of URTIs, including the common cold, when compared with placebo. However, this prebiotic combination does not seem to reduce the duration or severity of respiratory tract infections that do occur (99211). It is unclear if any effects are due to GOS, polydextrose, or the combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. It is unclear if oral GOS are beneficial in patients with anxiety. Details: One small clinical study in healthy females 18-25 years of age shows that taking GOS 5.5 grams daily for 4 weeks does not improve anxiety scores overall or in subgroups of individuals reporting high or low baseline levels of anxiety when compared with placebo (106640).
• Asthma. It is unclear if GOS, alone or in combination with fructo-oligosaccharides, are beneficial for preventing the development of asthma or recurrent wheeze in infants at risk for allergies. Details: One large clinical study in infants at risk for allergies shows that feeding 20 drops of syrup containing GOS 0.8 grams, in combination with one opened capsule of probiotic bacteria, daily for 6 months does not reduce the risk of developing atopic disease, including asthma, by the age of 2 years when compared with placebo (26707). However, another large clinical study in newborns at risk for atopic disease shows that feeding a formula containing a combination of GOS and fructo-oligosaccharides 8 grams/L as often as necessary for 6 months reduces the risk of developing recurrent wheezing, a risk factor for asthma, by 2 years of age when compared with placebo. Approximately 8% of infants given GOS formula developed recurrent wheeze, compared to about 21% of those given placebo formula (99223). These discrepant findings may be due to differences in measured outcomes, as well as the doses and products studied.
• Colorectal cancer. Although there has been interest in using oral GOS for the prevention of colorectal cancer, there is insufficient reliable information about the clinical effects of GOS for this purpose.
• Constipation. It is unclear if oral GOS, when taken with water or added to yogurt, are beneficial in patients with constipation. Details: Preliminary clinical research in adults with constipation shows that taking a specific GOS product (Biotis GOS, Friesland Campina) orally as 5.5-11 grams daily for three weeks does not increase stool frequency when compared with placebo (107730). Similarly, one very small clinical study in elderly females with constipation shows that consuming yogurt containing a specific syrup (Elix'or, Borculo Domo Ingredients) providing GOS 4.5 grams twice daily for 2 weeks does not improve defecation frequency, laxative use, or ease of defecation when compared with placebo (26706). Another small clinical study in elderly patients with mild constipation shows that consuming yogurt containing GOS 12 grams, prunes 12 grams, and linseed 6 grams daily for 3 weeks increases the frequency and ease of defecation and improves relief when compared with a traditional yogurt in elderly patients with mild constipation (21191). However, it is unclear if these findings are due to GOS, other ingredients, _or the combination.
• Depression. It is unclear if oral GOS are beneficial in patients with depression. Details: One small clinical trial in patients with major depressive disorder shows that taking GOS 5 grams daily for 8 weeks does not improve symptoms of depression when compared with placebo, and appears to be less effective when compared with a probiotic supplement containing Lactobacillus helveticus and Bifidobacterium longum (102506).
• Diarrhea. Although there has been interest in using oral GOS for the prevention and treatment of diarrhea, including travelers' diarrhea, there is insufficient reliable information about the clinical effects of GOS for this purpose.
• Insomnia. Oral GOS have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: One small crossover trial in adults with sleep disturbances shows that taking a combination product containing GOS 5.2 grams, whey protein 9.5 grams, large neutral amino acids 3.4 grams, and other vitamins and minerals one hour before bed nightly for 3 weeks does not improve sleep quality when compared with a control product containing no GOS and smaller amounts of protein, amino acids, vitamins, and minerals (106528).
• Iron deficiency anemia. GOS increases the absorption and tolerability of iron supplements, and may therefore be beneficial in patients with iron deficiency anemia. Details: Preliminary clinical research shows that taking GOS with iron supplements increases the absorption and tolerability of iron (102509,102510,107729). One small clinical trial in adult females shows that taking GOS 15 grams orally as a single dose increases the fractional iron absorption from oral ferrous sulfate, containing 104 mg iron, by 45% when compared with control (107729). Other clinical research in young, iron-deficient females, shows that giving GOS 963 mg/kg in addition to ferrous sulfate 30 ppm, increases mean hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, serum iron, serum transferrin, and total iron binding capacity when compared with ferrous sulfate alone (110599).
• Irritable bowel syndrome (IBS). It is unclear if oral GOS are beneficial in patients with IBS. Details: One small clinical trial in patients with IBS shows that taking GOS 1.4 grams daily while following a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) for 4 weeks increases the odds of adequate IBS symptom relief by 4.6-fold when compared with placebo plus a sham diet. However, no difference in rate of adequate symptom relief was reported when GOS plus the low FODMAP diet were compared with placebo plus the low FODMAP diet, suggesting that any benefits may have been due to the diet (106525).
• Metabolic syndrome. It is unclear if oral GOS are beneficial in patients with metabolic syndrome. Details: A small clinical study in overweight patients with metabolic syndrome shows that taking GOS 5.5 grams daily for 12 weeks does not improve most measures of metabolic syndrome when compared with placebo. Although levels of total cholesterol, triglycerides, and insulin were reduced by a small amount, these changes were not clinically meaningful (99219).
• Neonatal jaundice. It is unclear if oral GOS are beneficial for the treatment of neonatal jaundice. Details: A small clinical study in healthy infants with mild hyperbilirubinemia shows that providing a formula containing a combination of GOS and fructo-oligosaccharides 8 grams/L as often as necessary for 28 days reduces levels of bilirubin within 72 hours when compared with those given placebo formula. Whether GOS can reduce bilirubin levels in infants with very high levels of bilirubin is unknown, as these infants were excluded from this study (99222).
• Obesity. It is unclear if oral GOS improves weight loss in overweight or obese adults. Details: A small clinical study in overweight adults shows that taking GOS 6 grams, 12 grams, or 18 grams daily in oolong tea for 2 weeks has a small effect on appetite and weight loss when compared with oolong tea alone. Weight loss of 0.1-0.2 kg occurred over the study period, compared with no change in those taking oolong tea alone (99217).
• Osteoporosis. Although there has been interest in using oral GOS for osteoporosis, there is insufficient reliable information about the clinical effects of GOS for this purpose.
• Prematurity. It is unclear if oral GOS are beneficial for improving cognitive or motor development in premature infants. Details: A small clinical study in premature infants shows that adding a combination of GOS, fructo-oligosaccharides, and pectin acidic oligosaccharides up to 1.5 grams/kg daily to breast milk or formula for 30 days after birth does not improve cognitive or motor development outcomes at the age of 2 years when compared with placebo (99216).
• Ulcerative colitis. It is unclear if oral GOS are beneficial in patients with ulcerative colitis. Details: Preliminary clinical research in adults with ulcerative colitis shows that taking a specific GOS product (Bimuno GOS, Clasado Biosciences) orally 2.8 grams daily for 6 weeks does not increase clinical remission or improve IBD severity scores when compared with baseline. However, subgroup analyses suggest that taking GOS may reduce the frequency and urgency of loose stools. The validity of this study is limited by the lack of a comparator group (107728).
• Urticaria. It is unclear if oral GOS are beneficial for the prevention of urticaria in infants. Details: A small clinical study in newborns at risk for atopic disease shows that feeding a formula containing a combination of GOS and fructo-oligosaccharides 8 grams/L as often as necessary for 6 months reduces the risk of developing urticaria at 2 years of age when compared with placebo. Approximately 1.5% of infants in the GOS group developed urticaria, compared to 10.3% of those in the placebo group (99223). More evidence is needed to rate GOS for these uses.

(Read more about GALACTO-OLIGOSACCHARIDES (GOS))

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Constipation. It is unclear if oral polydextrose is beneficial in adults or children with constipation. Details: One small, low-quality, study in Japanese patients with dialysis-related constipation despite the use of laxatives shows that taking polydextrose 10 grams daily for 4 weeks increases weekly stool frequency from 3 stools to 8.5 stools, compared with an increase from 3.5 stools to 5 stools in the placebo group. However, taking polydextrose did not improve stool consistency, abdominal distention, or diarrhea when compared with placebo (98658). Other clinical research in adults with functional constipation shows that taking 4-12 grams of polydextrose orally daily for 2 weeks improves weekly stool frequency when compared with placebo. Preliminary subgroup analyses suggest that taking 12 grams of polydextrose may be more effective than lower doses. However, taking polydextrose did not improve colonic transit times or symptom scores when compared with placebo (106481). In contrast, clinical research in adults with chronic constipation shows that taking polydextrose (LitesseUltra, Danisco) 8 or 12 grams orally daily for 4 weeks does not improve stool consistency or frequency when compared with placebo (98659). Reasons for the conflicting results may relate to heterogeneity among the trial participants, including baseline constipation severity, and the studied dose and duration of polydextrose. In children aged 4-8 years with functional constipation, preliminary clinical research shows that taking a mixture of polydextrose 4.17 grams and fructo-oligosaccharides 0.45 grams orally daily for 45 days improves the weekly frequency of bowel movements, clinical manifestations of constipation, and quality of stool type when compared with baseline (106482). It is unclear if these effects are due to polydextrose, fructo-oligosaccharides, or the combination. Also, the validity of these findings is limited by the lack of a comparator group.
• Diabetes. It is unclear if oral polydextrose is beneficial in patients with diabetes. Details: Preliminary clinical research shows that drinking 200 mL of a beverage containing polydextrose (Litesse, Danisco Sweeteners) 40 grams/L twice daily for 12 weeks does not affect fasting plasma glucose or glycated hemoglobin (HbA1c) when compared with placebo in individuals with impaired glucose tolerance, impaired fasting glucose, or diet-treated type 2 diabetes (34118).
• Impaired glucose tolerance (Prediabetes). It is unclear if oral polydextrose is beneficial in patients with prediabetes. Details: Preliminary clinical research shows that drinking 200 mL of a beverage containing polydextrose (Litesse, Danisco Sweeteners) 40 grams/L twice daily for 12 weeks does not affect fasting plasma glucose or glycated hemoglobin (HbA1c) when compared with placebo in individuals with impaired glucose tolerance, impaired fasting glucose, or diet-treated type 2 diabetes (34118).
• Irritable bowel syndrome (IBS). Oral polydextrose has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with constipation-predominant IBS shows that consuming polydextrose 5.85 grams in a 350-mL sterilized probiotic beverage containing Lactobacillus helveticus once daily for 1 week does not improve constipation-related symptoms or intestinal transit time when compared with consuming the sterilized probiotic beverage alone (106480). Additionally, it is unclear how these findings would compare with the use of standard care. More evidence is needed to rate polydextrose 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.

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LIKELY SAFE ...when consumed in amounts commonly found in foods. GOS are found in various foods, including dairy products, legumes, and some root vegetables (26702,26732).

POSSIBLY SAFE ...when used orally and appropriately, short-term. GOS or foods fortified with GOS up to 20 grams daily have been safely used in clinical research for up to 30 days (21191,26706,26712,26727,99224,106526,106529,107715,107729). The European Food Safety Authority has concluded that consuming food products providing GOS up to 16.2 grams daily does not present safety concerns (106530). This agency has not evaluated the safety of higher doses in food products.

CHILDREN: POSSIBLY SAFE
when used orally in breast milk or infant formulas containing up to 7. 2 grams/L of GOS provided as the sole prebiotic or in combination with other prebiotics, including fructo-oligosaccharides or polydextrose, daily for 4-12 months (26708,26709,26710,26720,99211,99212,99215,99218,99222,99223,106527). ...when used in doses of up to 10 grams daily for 3 weeks in females 10-13 years of age (99210).

PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in amounts commonly found in foods.

PREGNANCY AND LACTATION: POSSIBLY SAFE
when used orally. GOS have been safely used in clinical research in doses of about 4.5 grams daily from week 25 of pregnancy until delivery (26721).

(Read more about GALACTO-OLIGOSACCHARIDES (GOS))

LIKELY SAFE ...when used orally as a food additive. Polydextrose is considered by the US Food and Drug Administration (FDA) to be safe when used as a food additive, provided a single serving contains less than 15 grams (26210).

POSSIBLY SAFE ...when used orally and appropriately in divided doses up to 50 grams daily for 12 weeks (27193,34118,98658,98659,106478). However, polydextrose can have laxative effects when taken orally in doses greater than 90 grams daily or greater than 50 grams as a single dose (27193,106478).

POSSIBLY UNSAFE ...when used orally in higher doses. The European Food Safety Authority (EFSA) has determined that there is no need for an acceptable daily intake of polydextrose when used as a food additive (106478). However, polydextrose can have laxative effects when taken orally in doses greater than 90 grams daily or greater than 50 grams as a single dose (27193,106478).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. Polydextrose appears to be safe for infants when administered at doses of 2-4 grams per liter of formula and for children aged 4-8 years when administered at doses of about 4 grams daily. While some studies show no adverse effects of polydextrose, others suggest a potential for increased abdominal pain, diarrhea, and eczema (26709,27200,106482).

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

(Read more about POLYDEXTROSE)

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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IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, GOS might reduce the effects of immunosuppressants.  Details Human and animal studies suggest that GOS may stimulate the immune system (26711,26723). This could theoretically alter the effects of immunosuppressant medications.

(Read more about GALACTO-OLIGOSACCHARIDES (GOS))

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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).

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General ...Orally, GOS seem to be well tolerated in infants, children, and adults.
Most Common Adverse Effects:
Orally: Bloating, constipation, diarrhea, flatulence, and increased stool frequency.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis in sensitive individuals.

Dermatologic ...Orally, giving a formula supplemented with 4 grams/L of GOS and polydextrose (1:1 ratio) to infants has been associated with an increased incidence of atopic dermatitis in one clinical study (26709). However, most other clinical research in infants at risk of atopy shows that GOS-containing formula may actually reduce the risk of developing atopic dermatitis (26707,26708,99223).

Gastrointestinal ...Orally, galacto-oligosaccharides may cause bloating, flatulence, and increased stool frequency (26706,26709,26724,99217,99222). Giving a formula supplemented with 4 grams/L of GOS and polydextrose (1:1 ratio) to infants has been associated with an increased incidence of gastrointestinal adverse effects, primarily constipation and diarrhea, in one clinical study (106527). However, it is unclear if this was due to GOS, polydextrose, or the combination.

Immunologic ...Orally, GOS have been rarely associated with allergic reactions, including anaphylaxis. Research in these patients shows that people who are previously sensitized to Blomia tropicalis, a common dust mite in Southeast Asia, may also experience allergic reactions after consumption of GOS. Blomia tropicalis contains glycosylated allergens that have IgE mediated cross-reactivity to GOS (102508).

Psychiatric ...Orally, giving infants a formula supplemented with 8 grams/L of a 50:33:17 mixture of polydextrose, GOS, and lactulose has been associated with increased infant irritability when compared with control formula (26709). However, it is not known if this was related to the GOS, other ingredients, or the combination. An increase in irritability did not occur in infants given a formula supplemented with 4 grams/L of polydextrose and GOS (1:1 ratio) (26709,106527).

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General ...Orally, polydextrose seems to be well tolerated when used in doses of less than 50 grams.
Most Common Adverse Effects:
Orally: Bloating, diarrhea, gas.

Gastrointestinal ...Orally, polydextrose may cause gas, bloating, and loose stools (27194,27208,27212). These adverse effects are more common when single doses of more than 50 grams or daily doses of more than 90 grams are used. Higher doses of polydextrose (90 grams/day or more) may also cause transient diarrhea in some people (27193).

Neurologic/CNS ...Orally, one participant in one clinical study complained of transient dizziness after eating yogurt containing polydextrose 12. 5 grams (98660).

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