Each bar contains: Probolic Plus sustained release protein matrix: Supro brand Soy Protein isolate , Milk Protein isolate , Calcium Caseinate , Whey Protein concentrate; Maltitol syrup; Chocolate flavored coating: Polydextrose , Palm Kernel Oil, Non-Fat Dry Milk solids, Cocoa powder, Soy Lecithin , Salt , Sucralose , Natural flavor; Chocolate Fudge: Maltitol syrup, Fructose , Vegetable coating: Hydrogenated Palm Kernel Oil, Lecithin , Sorbitan Monostearate , Polysorbate 60 ; Corn Syrup , Milk Protein isolate , Non-fat Dry Milk , Cocoa powder, Polydextrose , monoglycerides , Salt , Gellan Gum , Dicalcium Phosphate , Soy Lecithin , Sucralose , Natural and Artificial flavors; Cocoa powder, Glycerin ; Slow Carb Carbohydrate Blend: Tapioca starch, Rice Flour , Oat Flour (beta glucan); Gellan Gum , Sunflower Oil, malt extract, Fructo-Oligasaccharides , Maltodextrin , Salt , Soy Lecithin , Natural and Artificial flavors.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product Macrobolic Performance Bar (Crispy Peanut Caramel flavor, Crispy S'mores flavor). Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Macrobolic Performance Bar (Crispy Peanut Caramel flavor, Crispy S'mores flavor). Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally or intravenously and appropriately. Calcium is safe when used in appropriate doses (7555,12928,12946,95817). However, excessive doses should be avoided. The Institute of Medicine sets the daily tolerable upper intake level (UL) for calcium according to age as follows: Age 0-6 months, 1000 mg; 6-12 months, 1500 mg; 1-8 years, 2500 mg; 9-18 years, 3000 mg; 19-50 years, 2500 mg; 51+ years, 2000 mg (17506). Doses over these levels can increase the risk of side effects such as kidney stone, hypercalciuria, hypercalcemia, and milk-alkali syndrome. There has also been concern that calcium intake may be associated with an increased risk of cardiovascular disease (CVD) and coronary heart disease (CHD), including myocardial infarction (MI). Some clinical research suggests that calcium intake, often in amounts over the recommended daily intake level of 1000-1300 mg daily for adults, is associated with an increased risk of CVD, CHD, and MI (16118,17482,91350,107233). However, these studies, particularly meta-analyses, have been criticized for excluding trials in which calcium was administered with vitamin D (94137). Many of these trials also only included postmenopausal females. Other analyses report conflicting results, and have not shown that calcium intake affects the risk of CVD, CHD, or MI (92994,93533,97308,107231). Advise patients not to consume more than the recommended daily intake of 1000-1200 mg per day and to consider total calcium intake from both dietary and supplemental sources (17484). Also, advise patients taking calcium supplements to take calcium along with vitamin D (93533).
POSSIBLY UNSAFE ...when used orally in excessive doses. The National Academy of Medicine sets the daily tolerable upper intake level (UL) for calcium according to age as follows: 19-50 years, 2500 mg; 51 years and older, 2000 mg (17506). Doses over these levels can increase the risk of side effects such as kidney stones, hypercalciuria, hypercalcemia, and milk-alkali syndrome. There has also been concern that calcium intake may be associated with an increased risk of cardiovascular disease (CVD) and coronary heart disease (CHD), including myocardial infarction (MI). Some clinical research suggests that calcium intake, often in amounts over the recommended daily intake level of 1000-1300 mg daily for adults, is associated with an increased risk of CVD, CHD, and MI (16118,17482,91350,107233). However, these studies, particularly meta-analyses, have been criticized for excluding trials in which calcium was administered with vitamin D (94137). Many of these trials also only included postmenopausal females. Other analyses report conflicting results, and have not shown that calcium intake affects the risk of CVD, CHD, or MI (92994,93533,97308,107231). Advise patients to not consume more than the recommended daily intake of 1000-1200 mg per day and to consider total calcium intake from both dietary and supplemental sources (17484). Also, advise patients taking calcium supplements to take calcium along with vitamin D (93533).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Calcium is safe when used in appropriate doses (17506).
CHILDREN: POSSIBLY UNSAFE
when used orally in excessive doses.
The Institute of Medicine sets the daily tolerable upper intake level (UL) for calcium according to age as follows: 0-6 months, 1000 mg; 6-12 months, 1500 mg; 1-8 years, 2500 mg; 9-18 years, 3000 mg (17506). Doses over these levels can increase the risk of side effects such as kidney stones, hypercalciuria, hypercalcemia, and milk-alkali syndrome.
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately (945,1586,3263,3264,17506).
The World Health Organization (WHO) recommends prescribing oral calcium supplementation 1.5-2 grams daily during pregnancy to those with low dietary calcium intake to prevent pre-eclampsia (97347).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses.
The Institute of Medicine sets the same daily tolerable upper intake level (UL) for calcium according to age independent of pregnancy status: 9-18 years, 3000 mg; 19-50 years, 2500 mg (17506). Doses over these amounts might increase the risk of neonatal hypocalcemia-induced seizures possibly caused by transient neonatal hypoparathyroidism in the setting of excessive calcium supplementation during pregnancy, especially during the third trimester. Neonatal hypocalcemia is a risk factor for neonatal seizures (97345).
LIKELY SAFE ...when used orally and appropriately. Casein peptides have been safely used in clinical trials lasting up to 5 months (85648,103763,103764,103765,103770,103772).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Casein peptide formulas have been safely used in healthy, premature, and very low birth weight infants (91262,91264,91643,91673,91675).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately (13161,14306,14307,14308,15655,15752,17187,92271,92274,103247)(103250,108898). However, cocoa naturally contains caffeine, and caffeine may be unsafe when used orally in doses of more than 400 mg daily (11733,98806). While most cocoa products contain only small amounts of caffeine (about 2-35 mg per serving) (2708,3900), one cup of unsweetened, dry cocoa powder can contain up to 198 mg of caffeine (100515). To be on the safe side, cocoa should be used in amounts that provide less than 400 mg of caffeine daily. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine naturally found in ingredients such as cocoa does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. Cocoa and dark chocolate products worldwide also contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Advise patients to consume cocoa in moderation. ...when used topically. Cocoa butter is used extensively as a base for ointments and suppositories and is generally considered safe (11).
CHILDREN: POSSIBLY UNSAFE
when dark chocolate is used orally.
Cocoa and dark chocolate products worldwide contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Children are at increased risk of adverse effects from intake of lead and/or cadmium. There is insufficient reliable information available about the safety of other chocolate-based products that typically contain smaller quantities of cocoa.
PREGNANCY: POSSIBLY SAFE
when used orally in moderate amounts.
However, due to the caffeine content of cocoa preparations, intake should be closely monitored during pregnancy to ensure moderate consumption. Fetal blood concentrations of caffeine approximate maternal concentrations (4260). Some research has found that intrauterine exposure to even modest amounts of caffeine, based on maternal blood levels during the first trimester, is associated with a shorter stature in children ages 4-8 years (109846). While many cocoa products contain only small amounts of caffeine (about 2-35 mg per serving) (2708,3900), unsweetened, dry cocoa powder can contain up to 198 mg of caffeine per cup (100515). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, doses of up to 300 mg daily can be consumed during pregnancy without an increased risk of spontaneous abortion, still birth, preterm birth, fetal growth retardation, or congenital malformations (11733,98806). To be on the safe side, cocoa should be used in amounts that provide less than 300 mg of caffeine daily. Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as cocoa, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.
PREGNANCY: POSSIBLY UNSAFE
when used orally in large amounts.
Caffeine found in cocoa crosses the placenta producing fetal blood concentrations similar to maternal levels (4260). Consumption of caffeine in amounts over 300 mg daily is associated with a significantly increased risk of miscarriage in some studies (16014,98806). Additionally, high intake of caffeine during pregnancy have been associated with premature delivery, low birth weight, and loss of the fetus (6). While many cocoa products contain only small amounts of caffeine (about 2-35 mg per serving) (2708,3900), unsweetened, dry cocoa powder can contain up to 198 mg of caffeine per cup (100515). To be on the safe side, cocoa should be used in amounts that provide less than 300 mg of caffeine daily (2708). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as cocoa, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product. Cocoa and dark chocolate products worldwide also contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Large doses or excessive intake of cocoa should be avoided during pregnancy.
LACTATION: POSSIBLY SAFE
when used in moderate amounts or in amounts commonly found in foods.
Due to the caffeine content of cocoa preparations, intake should be closely monitored while breastfeeding. During lactation, breast milk concentrations of caffeine are thought to be approximately 50% of serum concentrations. Moderate consumption of cocoa would likely result in very small amounts of caffeine exposure to a nursing infant (6). Keep in mind that only the amount of ADDED caffeine must be stated on product labels. The amount of caffeine found in ingredients such as cocoa, which naturally contains caffeine, does not need to be provided. This can make it difficult to determine the total amount of caffeine in a given product.
LACTATION: POSSIBLY UNSAFE
when used orally in large amounts.
Consumption of excess chocolate (16 oz per day) may cause irritability and increased bowel activity in the infant (6026). Cocoa and dark chocolate products worldwide also contain heavy metals such as lead and cadmium. In the US, one ounce (approximately 28 grams) of most commercially available dark chocolate products tested contained levels of lead and/or cadmium above the maximum allowable dose level for California, with cadmium levels generally increasing with the percentage of cocoa (109847,109848,109849). Large doses or excessive intake of cocoa should be avoided during lactation.
LIKELY SAFE ...when used rectally and appropriately. Glycerol rectal suppositories and enemas are approved by the US Food and Drug Administration (FDA) for over-the-counter use to treat occasional constipation (15,272). ...when used topically and appropriately as a lotion, emulsion, or humectant (15,272,93754,93758,93759,99164).
POSSIBLY SAFE ...when used orally, short-term. Glycerol has been used with apparent safety in clinical trials at doses of up to 1.5 grams/kg (2474,2475,99162).
POSSIBLY UNSAFE ...when used intravenously. While some research suggests that intravenous glycerol can be safely administered for two consecutive days twice monthly for up to 6 months (106649), in another study, hemolysis was reported in 98% of patients treated with intravenous glycerol for acute ischemic stroke (2482).
CHILDREN: LIKELY SAFE
when used rectally and appropriately.
Glycerol rectal suppositories and enemas are approved by the US FDA for over-the-counter use to treat occasional constipation in children 2 years of age and older (15,272). ...when used topically and appropriately as an emulsion or humectant in children 1 month of age and older (15,272,93756).
CHILDREN: POSSIBLY SAFE
when used orally, short-term.
Glycerol has been used with apparent safety in clinical trials in children 2 months to 16 years of age at doses of 1.5 gram/kg, up to a maximum dose of 25 grams, taken every 6 hours (93762,93763).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Lecithin has Generally Recognized As Safe (GRAS) status in the US (2619,105544). ...when used orally and appropriately in medicinal amounts. Lecithin has been used safely in doses of up to 30 grams daily for up to 6 weeks (5140,5149,5152,5156,14817,14822,14838,19212). ...when used topically (4914).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in food amounts.
Lecithin has Generally Recognized As Safe (GRAS) status in the US (105544). There is insufficient reliable information available about the safety of medicinal amounts of lecithin during pregnancy or lactation; avoid using.
LIKELY SAFE ...when used orally and appropriately in food amounts (4960,4969,5792,5797). Oat bran has Generally Recognized as Safe (GRAS) status in the US (4912). Whole grain oats 50-100 grams daily have been used for up to 1 year without serious adverse effects (97520).
POSSIBLY SAFE ...when used topically and appropriately (12). Lotion containing colloidal oat 1% has been used topically without adverse effects for up to 6 weeks (97518,103340). There is insufficient reliable information available about the safety of oats when used orally in medicinal amounts.
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in food amounts (5792,5797).
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.
LIKELY SAFE ...when soy protein is used orally and appropriately. Soy protein products in doses up to 60 grams, providing up to 185 mg isoflavones, daily have been safely used in studies lasting up to 16 weeks (842,2293,2294,2296,3025,3402,3977,4755,6412,8530)(10372,11805).
POSSIBLY SAFE ...when soy extracts are used orally and appropriately, short-term. Soy extracts containing concentrated isoflavones in doses of 35-120 mg daily have been used with apparent safety for up to 6 months (4751,6455,7802,12040,12048,13209,95994,95999).
CHILDREN: LIKELY SAFE
when consumed in amounts commonly found in foods or as a component of infant formula (3400,4912,7331).
Soy milk that's not designed for infants should not be used as a substitute for infant formula. Regular soy milk can lead to nutrient deficiencies (12045). Most evidence shows that exposure to soy formula or other soy products in infancy does not cause early onset of puberty or health or reproductive problems later in life (7331,11080,108245). However, some small cohort studies have suggested that higher soy intake during childhood may be associated with an increased risk of precocious puberty (108240) and may be weakly correlated with the development of breasts in children less than 2 years of age (75520). This is in contrast to an observational study in Chinese children ages 7-9 years which suggests that higher soy intake is associated with delayed puberty (108252). One small cohort study has also found that use of soy infant formula may be associated with an increased risk of endometriosis in adulthood, although endometriosis was also correlated with prematurity, which may have confounded the findings (101803).
CHILDREN: POSSIBLY UNSAFE
when used orally as an alternative to cow's milk in children with severe milk allergy (75359).
Although soy protein-based infant formulas are often promoted for children with milk allergy, children with a severe allergy to cow's milk are also frequently sensitive to soy protein (9883). There is insufficient reliable information available about the safety of soy products when used in amounts higher than typical food quantities for children.
PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods (4912).
PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts.
Soy contains mildly estrogenic constituents (3373,3988,3989,3990,3994,6029,75303). Theoretically, therapeutic use of soy might adversely affect fetal development; avoid using.
LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (4912).
A single 20-gram dose of roasted soybeans, containing 37 mg isoflavones, produces four to six times less isoflavones in breast milk than provided in a soy-based infant formula (2290). There is insufficient reliable information available about the safety of long-term use of therapeutic amounts of soy during lactation.
LIKELY SAFE ...when used orally and appropriately in amounts commonly found in foods. When used as a substitute for other dietary oils, the recommended intake of high-oleic acid sunflower oil is 20 grams (1.5 tablespoons) daily (9780,98563). ...when used topically and appropriately, short-term. Sunflower oil has been applied to the skin twice daily for up to 6 weeks (76687). There is insufficient reliable information available about the safety of sunflower oil when used as an oral rinse.
CHILDREN: LIKELY SAFE
when used orally and appropriately in amounts commonly found in foods.
CHILDREN: POSSIBLY SAFE
when applied topically and appropriately, short-term.
Sunflower oil has been applied to the skin of infants daily for up to 2 months (96144,96145,105524,108143). There is insufficient reliable information available about the safety of sunflower oil when used orally in larger amounts as medicine.
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately in amounts commonly found in foods.
There is insufficient reliable information available about the safety of sunflower oil when used in amounts greater than those found in food.
LIKELY SAFE ...when used orally in the amounts commonly found in food (92944,92946). Tapioca has generally recognized as safe (GRAS) status in the US (92949).
POSSIBLY SAFE ...when used orally in medicinal amounts, short-term. Specific forms of tapioca, including tapioca maltodextrin and tapioca resistant maltodextrin, have been used with apparent safety at doses up to 25 grams daily and 7.7 grams daily, respectively, for up to 12 weeks (108895). Single doses of up to 50 grams have also been used with apparent safety (108894).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in the amounts commonly found in food (92944,92946).
There is insufficient reliable information available about the safety of tapioca when used in larger amounts as medicine during pregnancy or lactation; avoid use.
LIKELY SAFE ...when used orally and appropriately. Whey protein up to 30 grams has been safely used in clinical trials for up to 6 months (4930,16728,16729,105587).
CHILDREN: LIKELY SAFE
when used orally and appropriately as a dietary protein in food or infant formula.
Hydrolyzed whey protein-based formula has been safely used in infants for up to 6 months in clinical trials (4927,105585,105594).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Macrobolic Performance Bar (Crispy Peanut Caramel flavor, Crispy S'mores flavor). Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Calcium citrate might increase aluminum absorption and toxicity. Other types of calcium do not increase aluminum absorption.
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Calcium citrate can increase the absorption of aluminum when taken with aluminum hydroxide. The increase in aluminum levels may become toxic, particularly in individuals with kidney disease (21631). However, the effect of calcium citrate on aluminum absorption is due to the citrate anion rather than calcium cation. Calcium acetate does not appear to increase aluminum absorption (93006).
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Calcium reduces the absorption of bisphosphonates.
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Advise patients to take bisphosphonates at least 30 minutes before calcium, but preferably at a different time of day. Calcium supplements decrease absorption of bisphosphonates (12937).
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Taking calcipotriene with calcium might increase the risk for hypercalcemia.
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Calcipotriene is a vitamin D analog used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia (12938). Theoretically, combining calcipotriene with calcium supplements might increase the risk of hypercalcemia.
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Intravenous calcium may decrease the effects of calcium channel blockers; oral calcium is unlikely to have this effect.
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Intravenous calcium is used to decrease the effects of calcium channel blockers in the management of overdose. Intravenous calcium gluconate has been used before intravenous verapamil (Isoptin) to prevent or reduce the hypotensive effects without affecting the antiarrhythmic effects (6124). But there is no evidence that dietary or supplemental calcium when taken orally interacts with calcium channel blockers (12939,12947).
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Co-administration of intravenous calcium and ceftriaxone can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys.
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Avoid administering intravenous calcium in any form, such as parenteral nutrition or Lactated Ringers, within 48 hours of intravenous ceftriaxone. Case reports in neonates show that administering intravenous ceftriaxone and calcium can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys. In several cases, neonates have died as a result of this interaction (15794,21632). So far there are no reports in adults; however, there is still concern that this interaction might occur in adults.
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Using intravenous calcium with digoxin might increase the risk of fatal cardiac arrhythmias.
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Theoretically, calcium may reduce the therapeutic effects of diltiazem.
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Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation (10574). Theoretically, calcium might increase this risk of hypercalcemia and reduce the effectiveness of diltiazem.
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Calcium seems to reduce levels of dolutegravir.
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Advise patients to take dolutegravir either 2 hours before or 6 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium carbonate 1200 mg concomitantly with dolutegravir 50 mg reduces plasma levels of dolutegravir by almost 40%. Calcium appears to decrease levels of dolutegravir through chelation (93578).
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Calcium seems to reduce levels of elvitegravir.
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Advise patients to take elvitegravir either 2 hours before or 2 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium along with elvitegravir can reduce blood levels of elvitegravir through chelation (94166).
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Calcium seems to reduce the absorption and effectiveness of levothyroxine.
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Theoretically, concomitant use of calcium and lithium may increase this risk of hypercalcemia.
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Clinical research suggests that long-term use of lithium may cause hypercalcemia in 10% to 60% of patients (38953). Theoretically, concomitant use of lithium and calcium supplements may further increase this risk.
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Calcium seems to reduce the absorption of quinolone antibiotics.
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Calcium may reduce levels of raltegravir.
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Pharmacokinetic research shows that taking a single dose of calcium carbonate 3000 mg along with raltegravir 400 mg twice daily modestly decreases the mean area under the curve of raltegravir, but the decrease does not necessitate a dose adjustment of raltegravir (94164). However, a case of elevated HIV-1 RNA levels and documented resistance to raltegravir has been reported for a patient taking calcium carbonate 1 gram three times daily plus vitamin D3 (cholecalciferol) 400 IU three times daily in combination with raltegravir 400 mg twice daily for 11 months. It is thought that calcium reduced raltegravir levels by chelation, leading to treatment failure (94165).
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Calcium seems to reduce the absorption of sotalol.
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Advise patients to separate doses by at least 2 hours before or 4-6 hours after calcium. Calcium appears to reduce the absorption of sotalol, probably by forming insoluble complexes (10018).
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Calcium seems to reduce the absorption of tetracycline antibiotics.
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Advise patients to take oral tetracyclines at least 2 hours before, or 4-6 hours after calcium supplements. Taking calcium at the same time as oral tetracyclines can reduce tetracycline absorption. Calcium binds to tetracyclines in the gut (1843).
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Taking calcium along with thiazides might increase the risk of hypercalcemia and renal failure.
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Thiazides reduce calcium excretion by the kidneys (1902). Using thiazides along with moderately large amounts of calcium carbonate increases the risk of milk-alkali syndrome (hypercalcemia, metabolic alkalosis, renal failure). Patients may need to have their serum calcium levels and/or parathyroid function monitored regularly.
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Theoretically, calcium may reduce the therapeutic effects of verapamil.
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Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation (10574). Theoretically, use of calcium supplements may increase this risk of hypercalcemia and reduce the effectiveness of verapamil.
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Theoretically, combining these casein peptides with antihypertensive drugs might increase the risk of hypotension.
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Theoretically, taking cocoa with ACEIs might increase the risk of adverse effects.
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Theoretically, cocoa might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
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Cocoa contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine. It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests. However, methylxanthines appear more likely to interfere with dipyridamole than adenosine-induced stress testing (11771).
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Theoretically, concomitant use might increase levels and adverse effects of caffeine.
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Cocoa contains caffeine. Alcohol reduces caffeine metabolism. Concomitant use of alcohol can increase caffeine serum concentrations and the risk of caffeine adverse effects (6370).
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Theoretically, cocoa may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Clinical research shows that intake of cocoa can inhibit platelet adhesion, aggregation, and activity (6085,17076,41928,41948,41957,41958,41995,42014,42070,42145)(111526) and increase aspirin-induced bleeding time (23800). For patients on dual antiplatelet therapy, cocoa may enhance the inhibitory effect of clopidogrel, but not aspirin, on platelet aggregation (111526).
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Theoretically, taking cocoa with antihypertensive drugs might increase the risk of hypotension.
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Theoretically, large amounts of cocoa might increase the cardiac inotropic effects of beta-agonists.
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Cocoa contains caffeine. Theoretically, large amounts of caffeine might increase cardiac inotropic effects of beta-agonists (15). A case of atrial fibrillation associated with consumption of large quantities of chocolate in a patient with chronic albuterol inhalation abuse has also been reported (42075).
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Theoretically, concomitant use might increase the effects and adverse effects of caffeine in cocoa.
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Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in cocoa.
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Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Caffeine is metabolized by cytochrome P450 1A2 (CYP1A2) (3941,5051,11741,23557,23573,23580,24958,24959,24960,24962), (24964,24965,24967,24968,24969,24971,38081,48603). Theoretically, drugs that inhibit CYP1A2 may decrease the clearance rate of caffeine from cocoa and increase caffeine levels.
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Theoretically, cocoa might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
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Cocoa contains caffeine. Caffeine may inhibit dipyridamole-induced vasodilation (11770,11772). It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests (11770). Methylxanthines appear more likely to interfere with dipyridamole than adenosine-induced stress testing (11771).
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Theoretically, disulfiram might increase the risk of adverse effects from caffeine.
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Cocoa contains caffeine. In human research, disulfiram decreases the rate of caffeine clearance (11840).
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Theoretically, using cocoa with diuretic drugs might increase the risk of hypokalemia.
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Theoretically, concomitant use might increase the risk for stimulant adverse effects.
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Theoretically, estrogens might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Estrogen inhibits caffeine metabolism (2714).
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Theoretically, fluconazole might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022).
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Theoretically, cocoa might increase the levels and adverse effects of flutamide.
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Cocoa contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide (23553).
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Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Fluvoxamine reduces caffeine metabolism (6370).
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Theoretically, abrupt cocoa withdrawal might increase the levels and adverse effects of lithium.
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Theoretically, methoxsalen might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Methoxsalen can reduce caffeine metabolism (23572).
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Theoretically, metformin might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Animal research suggests that metformin can reduce caffeine metabolism (23571).
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Theoretically, mexiletine might increase the levels and adverse effects of caffeine.
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Theoretically, concomitant use might increase the risk of a hypertensive crisis.
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Cocoa contains caffeine. Large amounts of caffeine with MAOIs might precipitate a hypertensive crisis (15).
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Theoretically, concomitant use might increase the risk of hypertension.
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Cocoa contains caffeine. Concomitant use of caffeine and nicotine has been shown to have additive cardiovascular effects, including increased heart rate and blood pressure. Blood pressure was increased by 10.8/12.4 mmHg when the agents were used concomitantly (36549).
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Theoretically, cocoa might decrease the effects of pentobarbital.
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Cocoa contains caffeine. Caffeine might negate the hypnotic effects of pentobarbital (13742).
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Theoretically, cocoa might reduce the effects of phenobarbital and increase the risk for convulsions.
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Theoretically, phenothiazines might increase the levels and adverse effects of caffeine.
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Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
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Theoretically, cocoa might reduce the effects of phenytoin and increase the risk for convulsions.
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Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
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Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
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Cocoa contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2, and concomitant use might reduce metabolism of one or both agents (11739).
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Theoretically, concomitant use might increase stimulant adverse effects.
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Cocoa contains caffeine. Concomitant use might increase the risk of stimulant adverse effects (11832).
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Theoretically, terbinafine might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Terbinafine decreases the rate of caffeine clearance (11740).
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Theoretically, cocoa might increase the levels and adverse effects of theophylline.
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Theoretically, cocoa tea might increase the levels and adverse effects of tiagabine.
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Cocoa contains caffeine. Animal research suggests that chronic caffeine administration can increase the serum concentrations of tiagabine. However, concomitant use does not seem to reduce the antiepileptic effects of tiagabine (23561).
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Theoretically, ticlopidine might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. In vitro evidence suggests that ticlopidine can inhibit caffeine metabolism (23557). However, this effect has not been reported in humans.
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Theoretically, cocoa might reduce the effects of valproate and increase the risk for convulsions.
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Theoretically, verapamil might increase the levels and adverse effects of caffeine.
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Cocoa contains caffeine. Verapamil increases plasma caffeine concentrations by 25% (11741).
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Theoretically, oats may have additive effects with antidiabetic agents and might increase the risk of hypoglycemia.
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Concomitant use of oats and insulin might increase the risk of hypoglycemia.
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In patients with insulin-dependent type 2 diabetes, taking oats 100 grams daily for 2 days reduces the insulin dose required to achieve metabolic control (103336).
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Theoretically, antibiotics may decrease the activity of soy isoflavones.
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Intestinal bacteria are responsible in part for converting soy isoflavones into their active forms. Antibiotics may decrease the amount of intestinal bacteria and decrease its ability to convert isoflavones (7657).
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Soy can lower blood glucose and have additive effects with antidiabetes drugs.
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Clinical research shows that whole soy diets and soy-based meals reduce fasting glucose levels in diabetic and non-diabetic individuals (75268,75296,75378,75493,96001). Also, individuals following a soy-based meal replacement plan seem to require lower doses of sulfonylureas and metformin to manage blood glucose levels when compared with individuals following a diet plan recommended by the American Diabetes Association (75268).
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Theoretically soy protein may have additive effects with antihypertensive drugs and increase the risk of hypotension.
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Theoretically, soy might reduce the clearance of caffeine.
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Soy contains genistein. Taking genistein 1 gram daily for 14 days seems to inhibit caffeine clearance and metabolism in healthy females (23582). This effect has been attributed to inhibition of the cytochrome P450 1A2 (CYP1A2) enzyme, which is involved in caffeine metabolism. It is unclear if this effect occurs with the lower amounts of genistein found in soy.
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Soy might modestly induce CYP2C9 enzymes. However, this effect does not seem to be clinically significant.
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In vitro research suggests that an unhydrolyzed soy extract might induce CYP2C9. However, the significance of this interaction is likely minimal. In healthy females taking a specific extract of soy (Genistein Soy Complex, Source Naturals), blood levels of losartan, a CYP2C9 substrate, were not significantly affected (16825).
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Theoretically, soy might have additive effects when used with diuretic drugs.
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Animal research suggests that genistein, a soy isoflavone, increases diuresis within 6 hours of subcutaneous administration in rats. The effects seem to be similar to those of furosemide (75604). This effect has not been reported in humans.
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Theoretically, soy might competitively inhibit the effects of estrogen replacement therapy.
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Soy contains phytoestrogens and has been shown to have estrogenic activity in some patients (3860). Although this has not been demonstrated in humans, theoretically, concomitant use of soy with estrogen replacement therapy might reduce the effects of the estrogen replacement therapy.
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Soy products might reduce the absorption of levothyroxine in some patients.
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Preliminary clinical research and a case report suggest that soy-based formulas inhibit the absorption of levothyroxine in infants with congenital hypothyroidism (20636,20637,75548,90959). A levothyroxine dosage increase may be needed for infants with congenital hypothyroidism while using soy-based formulas, and the dose may need to be reduced when soy-based formulas are no longer administered. However, in postmenopausal adults, clinical research shows that taking a single dose of soy extract containing isoflavones 60 mg along with levothyroxine does not affect the oral bioavailability of levothyroxine (95996).
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Taking soy products containing high amounts of tyramine along with MAOIs can increase the risk of hypertensive crisis.
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Fermented soy products such as tofu and soy sauce contain tyramine, a naturally occurring chemical that affects blood pressure regulation. The metabolism of tyramine is decreased by MAOIs. Consuming more than 6 mg of tyramine while taking an MAOI can increase the risk of hypertensive crisis (15649). The amount of tyramine in fermented soy products is usually less than 0.6 mg per serving; however, there can be significant variation depending on the specific product used, storage conditions, and length of storage. Storing one brand of tofu for a week can increase tyramine content from 0.23 mg to 4.8 mg per serving (15649,15701,15702). Advise patients taking MAOIs to avoid fermented soy products that contain high amounts of tyramine.
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Theoretically, combining soy isoflavones with transdermal progesterone may worsen bone density.
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Clinical research suggests that significant bone loss may occur in females with osteoporosis who receive a combination of transdermal progesterone with soy milk containing isoflavones when compared with placebo, soy milk alone, or progesterone alone (69859).
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Theoretically, estrogenic soy isoflavones might alter the effects of tamoxifen.
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Laboratory research suggests that genistein and daidzen, isoflavones from soy, can antagonize the antitumor effects of tamoxifen under some circumstances (7072,14362,8966); however, soy isoflavones might have different effects when used at different doses. A relatively low in vitro concentration of soy isoflavones such as 1 microM/L seems to interfere with tamoxifen, whereas high in vitro concentrations such as those >10 microM/L might actually enhance tamoxifen effects. People on a high-soy diet have soy isoflavones levels ranging from 0.1-6 microM/L. Until more is known, advise patients taking tamoxifen to avoid therapeutic use of soy products.
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Theoretically, soy might interfere with the effects of warfarin.
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Soy milk has been reported to decrease the international normalized ratio (INR) in a patient taking warfarin. The mechanism of this interaction is not known (9672). However, animal and in vitro research suggests that soy may also inhibit platelet aggregation (3992). Dosing adjustments for warfarin may be necessary.
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Theoretically, sunflower oil might decrease the effectiveness of antidiabetes medications.
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A diet using sunflower oil as a fat source can cause increased fasting blood glucose levels in patients with type 2 diabetes (8132). Dose adjustments to diabetes medications might be necessary.
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Theoretically, whey protein might reduce the absorption of bisphosphonates.
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Theoretically, whey protein might decrease levodopa absorption.
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Theoretically, whey protein might decrease quinolone absorption.
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Theoretically, whey protein might decrease tetracycline absorption.
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Below is general information about the adverse effects of the known ingredients contained in the product Macrobolic Performance Bar (Crispy Peanut Caramel flavor, Crispy S'mores flavor). Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally and intravenously, calcium is well-tolerated when used appropriately.
Most Common Adverse Effects:
Orally: Belching, constipation, diarrhea, flatulence, and stomach upset.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about calciphylaxis and kidney stones.
Cardiovascular
...There has been concern that calcium intake may be associated with an increased risk of cardiovascular disease (CVD) and coronary heart disease (CHD), including myocardial infarction (MI).
Some clinical research suggests that calcium intake, often in amounts over the recommended daily intake level of 1000-1300 mg daily for adults, is associated with an increased risk of CVD, CHD, and MI (16118,17482,91350,107233). However, these results, particularly meta-analyses, have been criticized for excluding trials in which calcium was administered with vitamin D (94137). Many of these trials also only included postmenopausal females. Other analyses report conflicting results, and have not shown that calcium intake affects the risk of CVD, CHD, or MI (92994,93533,97308,107231). Reasons for these discrepancies are not entirely clear. It may relate to whether calcium is taken as monotherapy or in combination with vitamin D. When taken with vitamin D, which is commonly recommended, calcium supplementation does not appear to be associated with an increased risk of CVD, CHD, or MI (93533,107231). Also, the association between calcium supplementation and CVD, CHD, or MI risk may be influenced by the amount of calcium consumed as part of the diet. Supplementation with calcium may be associated with an increased risk of MI in people with dietary calcium intake above 805 mg daily, but not in those with dietary calcium intake below 805 mg daily (17482). To minimize the possible risk of CVD, CHD, or MI, advise patients not to consume more than the recommended daily intake of 1000-1200 mg and to consider total calcium intake from both dietary and supplemental sources (17484). While dietary intake of calcium is preferred over supplemental intake, advise patients who require calcium supplements to take calcium along with vitamin D, as this combination does not appear to be associated with an increased risk of MI (93533).
Rarely, calcium intake can increase the risk of calciphylaxis, which usually occurs in patients with kidney failure. Calciphylaxis is the deposition of calcium phosphate in arterioles, which causes skin ulcers and skin necrosis. In a case report, a 64-year-old female with a history of neck fracture, sepsis, and ischemic colitis presented with painful leg ulcers due to calciphylaxis. She discontinued calcium and vitamin D supplementation and was treated with sodium thiosulfate and supportive care (95816).
Gastrointestinal ...Orally, calcium can cause belching, flatulence, nausea, gastrointestinal discomfort, and diarrhea (1824,1843,12950,38803). Although constipation is frequently cited as an adverse effect of calcium, there is no scientific substantiation of this side effect (1824,1843,1844,1845,12950,38978). Calcium carbonate has been reported to cause acid rebound, but this is controversial (12935,12936).
Oncologic ...There is some concern that very high doses of calcium might increase the risk of prostate cancer. Some epidemiological evidence suggests that consuming over 2000 mg/day of dietary calcium might increase the risk for prostate cancer (4825,12949). Additional research suggests that calcium intake over 1500 mg/day might increase the risk of advanced prostate cancer and prostate cancer mortality (14132). Consumption of dairy products has also been weakly linked to a small increase in prostate cancer risk (98894). However, contradictory research suggests no association between dietary intake of calcium and overall prostate cancer risk (14131,14132,104630). More evidence is needed to determine the effect of calcium, if any, on prostate cancer risk.
Renal ...Kidney stones have been reported in individuals taking calcium carbonate 1500 mg daily in combination with vitamin D 2000 IU daily for 4 years (93943).
General ...Orally, casein peptides are well tolerated in infants and adults. Adverse effects reported in clinical trials did not occur more frequently than with placebo.
General
...Orally and topically, cocoa is generally well tolerated.
Most Common Adverse Effects:
Orally: Borborygmi, constipation, diuresis, gastrointestinal discomfort, headaches, and nausea.
Serious Adverse Effects (Rare):
Orally: Tachycardia.
Cardiovascular ...Some cases of increased heart rate have been reported with oral cocoa use (13161,42132).
Dermatologic ...In some cases, when taken orally, cocoa can cause allergic skin reactions (13161). Topically, cocoa butter has occasionally caused a rash. In animals, it has been shown to block pores and cause acne; however, this has not been found in humans (11).
Gastrointestinal ...In human trials, chocolate consumption was associated with a higher incidence of flatulence, irritable bowel syndrome, upset stomach, gastric upset, borborygmi (a gurgling noise made by fluid or gas in the intestines), bloating, nausea, vomiting, and constipation or obstipation (41986,42221,41921,1374,42220,1373,42099,42097,42156,42123,18229,42169,42111). Chocolate consumption has been implicated as a provoking factor in gastroesophageal reflux disease (GERD) (41974,42005,41946,1374). Unpalatability has been reported (42079,42169). Consumption of chocolate and other sweet foods may lead to increased dental caries (42129,42030).
Genitourinary ...In some cases, when taken orally, cocoa can cause increased urination (13161).
Neurologic/CNS ...In some cases, when taken orally, cocoa can cause shakiness and might trigger migraine and other headaches (13161,42169,92271).
Other ...Due to the high sugar and caloric content of chocolate, there is concern about weight gain in people who consume large amounts of chocolate (17187).
General
...Orally, rectally, and topically, glycerol seems to be well tolerated.
Intravenously, glycerol may be unsafe.
Most Common Adverse Effects:
Orally: Bloating, diarrhea, nausea, vomiting, dizziness, and headache.
Topically: Burning, irritation, and pruritus.
Intravenously: Hemolysis in patients with acute ischemic stroke.
Dermatologic ...Topically, glycerol has been reported to cause burning, irritation, and pruritus (93754,93756). Rectally, the regular administration of glycerol 50% enemas has been reported to cause generalized urticaria in at least two patients; in both patients, symptoms resolved after discontinuation (110019,110025).
Gastrointestinal ...Orally, glycerol can cause bloating, nausea, vomiting, thirst, and diarrhea (15,2475).
Hematologic ...Intravenously, glycerol has been reported to caused hemolysis in people treated for acute ischemic stroke (2480,2482).
Neurologic/CNS ...Orally, glycerol can cause mild headache and dizziness (15,2475).
General
...Orally, lecithin is well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, fullness, and nausea.
Dermatologic ...Orally, lecithin can cause allergic skin reactions in people with egg or soy allergies (15705).
Gastrointestinal ...Orally, lecithin may cause abdominal pain, diarrhea, fullness, and nausea (5140,6243,14817,14822,14838,19204,59281).
Neurologic/CNS ...Orally, lecithin caused CNS complaints and agitation in one patient in a clinical trial (59261).
General
...Orally, oats are well tolerated.
Most Common Adverse Effects:
Orally: Abdominal distension, bloating, flatulence, and unpleasant taste.
Topically: Burning, contact dermatitis, itching, and redness.
Dermatologic ...Topically, oat-containing preparations can cause contact dermatitis (12515). Redness, burning, and itchiness have also been reported (103340).
Gastrointestinal
...When consumed orally, oats provide fiber.
Increasing fiber in the diet can cause flatulence, bloating, abdominal distention, and unpleasant taste. To minimize side effects, doses should be slowly titrated to the desired level. These adverse effects usually subside with continued use (12514).
In patients who have difficulty chewing food, or those with conditions that decrease small bowel motility, oat bran may cause bezoars (concretions) and intestinal obstruction. Oats and oat bran are unlikely to cause obstruction without other causative factors (4979,4985).
Immunologic ...In a case report, a 45-year-old male developed acute generalized urticaria, facial angioedema, and dyspnea immediately after consuming oat flour. The reaction resolved after emergency care for anaphylaxis. Further investigation revealed an IgE-mediated hypersensitivity reaction to oat proteins (113490).
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).
General
...Orally, soy is well tolerated.
Most Common Adverse Effects:
Orally: Bloating, constipation, diarrhea, and nausea.
All ROAs: Allergic reactions.
Endocrine
...In the 1950s and 1960s, cases of altered thyroid function, particularly goiter, were reported in children taking soy formula.
However, adding iodine to soy formula or replacing soy flour in formula with soy protein isolate has nearly eliminated the risk of altered thyroid function in most infants (75353,75651).
In adults, there is some evidence that soy intake can alter thyroid function. Results from one clinical trial suggests that consuming soybeans 30 grams daily for as little as one month can increase thyroid-stimulating hormone (TSH) and decrease thyroxine, causing diffuse goiters, constipation, fatigue, and lethargy in some Japanese men. Recovery was achieved by discontinuing soybean intake (75206,75353). There is also some evidence that soy inhibits thyroid hormone synthesis resulting in increased secretion of TSH in some postmenopausal patients (7806). However, this seems to only occur in people with iodine deficiency (6466,75311). In postmenopausal patients with normal levels of iodine, taking a soy extract for 6 months does not seem to significantly affect thyroid hormone levels (13010).
Evidence from a single case-control study suggests that consumption of soy-based formulas may be associated with an observed three-fold increase in the risk of breast development in Puerto Rican children less than 2 years-old (75520). The correlation has been attributed to the estrogenic activity of soy. However, other risk factors, including a maternal history of ovarian cysts and consumption of meat products were also associated with the increased risk of breast development prior to 2 years of age. Also, the investigators noted that in over half of the cases, the child had not been exposed to soy or any of the other risk factors. Therefore, factors other than soy consumption may be more strongly associated with the increased risk of breast development prior to 2 years of age.
Gastrointestinal ...Gastrointestinal upset, such as constipation, diarrhea, bloating, and nausea are the most common side effects of soy (2297,11033,11082,15851,75491,95999). Reports of "bad taste" and taste intolerance have also been documented in clinical research (15851,39007,75491). Firmer stools, diarrhea, colitis, and intestinal mucosal damage has been reported in infants fed soy protein formula (75161,75448,75516,75525).
Genitourinary
...Orally, soy might increase discomfort during menstrual periods.
Evidence from a small, retrospective cohort study has found that consuming soy formula as an infant may slightly increase the duration and discomfort of menstrual periods later in life. However, the investigators noted that these differences may not be clinically significant (7331).
Orally, frequent soy consumption might be a risk factor for uterine leiomyoma, an estrogen-dependent benign tumor located on the uterus. Observational research found that consumption of soy milk or soybean at least four times weekly is associated with a 7-fold increased odds of uterine leiomyoma (98869).
There is some concern that use of soy-based formulas in infants might result in long-term health complications. However, results from a retrospective cohort study has found that intake of soy-based formula as an infant does not affect height, weight, body mass index, pubertal maturation, menstrual history, or pregnancy history, nor does it increase the risk of reproductive organ disorders, hormonal disorders, libido dysfunction, or birth defects in the offspring of adults who received soy formula as infants (7331,11080). Additionally, research in adults shows that urinary phytoestrogens are not associated with endometriosis risk (101804). However, some population research has found that regular exposure to soy-based formulas during infancy is associated with an increased risk for endometriosis (101803).
Immunologic
...Orally, soy can cause allergic reactions such as skin rash and itching in some people (6412).
In an 11-year-old female, allergy to soy protein resulting in a delayed itching papular rash was thought to be responsible for the reaction to injected benzathine benzylpenicillin containing possible soy protein-contaminated soy lecithin (96422).
Topically, soy-based ingredients were responsible for the development of hand atopic dermatitis in a young female using cosmetic lotions in the workplace. Percutaneous sensitization resulted in the development of anaphylaxis to oral soy (96000).
Neurologic/CNS ...Orally, one clinical study showed that insomnia was more common in postmenopausal adults taking soy isoflavone supplements when compared with those receiving placebo (9917). Some research suggests that dietary consumption of tofu during midlife might decrease cognitive function in later years. Evidence from one retrospective cohort study suggests that males who consume at least two servings of tofu weekly during midlife have increased risk of cognitive impairment in late life (19% vs. 4%) compared to those who consume tofu less frequently. Although the effect of tofu was considered to be marginal compared to other factors such as age, education, or history of stroke, results from the study suggest that the effect of significant midlife consumption of tofu is comparable to the effect of an age difference of 4 years or an education difference of 3 years. However, numerous other factors, such as lifestyle and health, could be involved (6415,6416). Therefore, these findings are too preliminary to be used as a basis for clinical recommendations.
Oncologic
...There is controversy about the role of soy in breast cancer.
Population studies suggest that soy is protective against breast cancer. Asian females who eat a traditional diet high in soy seem to have a lower risk of developing breast cancer (4590,5939,9674). Early exploratory studies have suggested that soy stimulates proliferation of normal human breast tissue (3980,3981). However, taking a soy tablet containing 50 mg soy isoflavones daily for 12 months does not alter mammographic or breast MRI tissue density in adults at high risk of breast cancer, with non-endocrine treated breast cancer, or previously treated for breast cancer and without evidence of recurrence (95999).
There is some concern that soy supplements, but not soy foods, might increase the risk of endometrial hyperplasia due to its estrogenic effects. Population and clinical research suggests that soy foods do not have a proliferative effect on endometrial cells (7358,2429,7654,9676,9917), and increased dietary soy and phytoestrogens are associated with reduced endometrial cancer risk (7338,10372). However, the effects seem to be different with concentrated soy isoflavone extract. While taking products providing isoflavones 120 mg daily for 6 months does not increase endometrial thickening (13209), taking higher doses such as isoflavones 150 mg daily for 5 years might increase the risk of simple endometrial hyperplasia (12105). However, there is no evidence that soy isoflavones increase the risk of atypical hyperplasia which has a much higher risk of developing into endometrial cancer than simple endometrial hyperplasia (12105,90973).
There is also concern that increased soy intake increases the risk for other types of cancer. Some observational research has found that higher dietary intake of soy is associated with a higher risk for bladder cancer and pancreatic cancer (9677,105609).
A meta-analysis of results from cohort and case-control studies evaluating the risk of stomach cancer related to consumption of fermented soy products is unclear and inconclusive. The highest quality data from cohort studies suggests that these products have no significant effect on stomach cancer (7340,7341). More research is required to determine if soy products have any correlation with stomach cancer.
Pulmonary/Respiratory ...Inhaled soy dust and soy hull aeroallergen can trigger symptoms of asthma and allergic rhinitis (5084,5085,5086).
General
...Orally and topically, sunflower oil is well tolerated.
Serious Adverse Effects (Rare):
Orally: Allergic reactions in sensitive individuals have been reported.
Immunologic ...Orally, sunflower oil can cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs. However, the protein content of sunflower oil is very low. In one case report, an allergic response to sunflower oil did not occur despite presenting with severe allergy and anaphylaxis to sunflower seed (108140).
General
...Orally, whey protein is generally well tolerated.
Most Common Adverse Effects:
Orally: Acne, bloating, cramps, diarrhea, fatigue, headache, nausea, reflux, reduced appetite, and thirst. Most adverse effects are dose-related.
Cardiovascular ...In one case report, use of an unclear quantity of whey protein over one month was thought to be probably responsible for the development of coronary embolism in three coronary arteries in a 33-year-old male with no history of atherosclerosis risk factors. The patient required treatment with intravenous glycoprotein IIb/IIIa inhibitor and heparin (96023).
Dermatologic ...Orally, whey protein has been reported to trigger the onset or worsening of acne. Multiple case reports in teenagers and young adults have associated intake of whey protein with the development of acne or the worsening of existing acneiform lesions. In these reports, the discontinuation of whey protein was typically associated with the clearance of acne lesions. In some cases, patients who were unresponsive to acne treatments while using whey protein became responsive after whey protein discontinuation (103965,103970,103971). Cow's milk, which is comprised of 20% whey protein, is also thought to exacerbate acne. It is theorized that this effect may be due to the growth factor and alpha-lactalbumin content of whey protein (103971,103982).
Gastrointestinal ...Orally, whey protein, especially in higher doses of 2. 3-6.5 grams/kg daily, may cause increased bowel movements, nausea, thirst, bloating, esophageal reflux, cramps, and reduced appetite (2640,85961,85702,86043,86074,86075,86084,86089,86095).
Hepatic ...In two case reports, acute cholestatic liver injury occurred after consumption of the combination of whey protein and creatine supplements (46701,90319).
Musculoskeletal ...In one case report, a 26-year-old male experienced fasciitis, or swelling of the forearms, hands, and legs, after consuming the supplement Pure Whey (85895).
Neurologic/CNS ...Orally, high doses of whey protein may cause tiredness or fatigue and headache (2640). Mild drowsiness has also been reported (86089,86092,86124).
