Cappuccino Comfort Fructose by Physicians Laboratories

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Each packet contains: Certified Isoflavone 160 mg • Soy Protein Isolate • Real Coffee Powder. Other Ingredients: Fructose, Sucrose, Natural and Artificial Flavor, Dutch Processed Cocoa, Soy Lecithin, Calcium Phosphate, Potassium chloride, Sodium Chloride, Xanthan Gum, Carboxymethylcellulose, Undegraded Carrageenan.

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Below is general information about the effectiveness of the known ingredients contained in the product Cappuccino Comfort Fructose. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

COFFEE

LIKELY EFFECTIVE

Mental alertness. Consumption of caffeinated coffee attenuates changes in alertness and cognitive capacity that occur throughout the day. It also improves mental performance and alertness following sleep deprivation. Details: Consumption of coffee and other caffeinated beverages seems to prevent a decline in alertness and cognitive capacity when consumed throughout the day (4221,4224). Caffeine can improve mental performance and alertness following prolonged sleep deprivation (10205). With respect to mental alertness while driving, some research shows that drinking a single cup of coffee containing 80 mg caffeine in 180 mL during a 15-minute rest after simulated driving for 2 hours reduces the amount of weaving and increases speed consistency in the 3rd and 4th hours of driving when compared with drinking decaffeinated coffee. Overall, the mental effort needed to drive, driving quality, and feelings of sleepiness appear to improve with caffeine consumption (93875).

POSSIBLY EFFECTIVE

Diabetes. Population research has found that consumption of caffeinated coffee is associated with a reduced risk of developing type 2 diabetes. Consumption of coffee also seems to be associated with a reduced risk of mortality in patients with type 2 diabetes. Details: Population research suggests that consumption of caffeinated coffee is associated with a dose-dependent reduced risk of developing type 2 diabetes (11353,11731,14313,38174,91040,91055,111040). Some research suggests that increasing coffee consumption by 1 cup daily is associated with a 6% to 9% reduction in the incidence of type 2 diabetes (91040,91055). In North American adults, consuming 6 or more cups of coffee daily is associated with a 29% lower risk of developing diabetes in females and a 54% lower risk in males (11353). Research in European adults suggests that drinking 5-6 cups of coffee daily appears to reduce diabetes risk by 61% in females and 30% in males. Drinking 10 or more cups daily reduces diabetes risk by 79% in females and 55% in males (11731). Additional research suggests that drinking 3-4 cups of coffee daily reduces the risk of diabetes by 23% to 42% when compared with drinking just 1 cup daily (14343,38174). An analysis of these and other cohort studies involving over 457,000 patients suggests that drinking 3-4 cups of coffee or decaffeinated coffee daily is associated with a 25% to 35% reduced risk of type 2 diabetes when compared with drinking 2 cups or less daily. Each additional cup of coffee consumed each day is associated with a 5% to 10% reduction in the incidence of type 2 diabetes (97368). Some population research in patients with previous gestational diabetes has also investigated the association between consumption of coffee and risk of developing type 2 diabetes. Research suggests that consumption of at least 4 cups of caffeinated coffee daily is associated with a 54% reduced risk of type 2 diabetes when compared with drinking no coffee. There is no association between consumption of decaffeinated coffee and type 2 diabetes risk (111040). Coffee consumption has also been evaluated in patients with type 2 diabetes, with mixed findings. Most population research suggests that coffee consumption is associated with a reduced risk of mortality in patients with type 2 diabetes. In one meta-analysis of observational studies, drinking high amounts of coffee was associated with a 24% reduction in mortality risk, with a 9% reduction for each additional cup of coffee (104595). In another meta-analysis, drinking up to 4 cups of coffee daily was associated with a 19% reduction in all-cause mortality and a 34% reduction in coronary heart disease (CHD) mortality when compared with not drinking coffee. Reductions in cardiovascular disease (CVD) mortality were only significant when one large study was excluded during sensitivity analyses (107836). Results of individual studies are conflicting (37805,97374,104589,104594). Additionally, a cross-sectional study in older adults with type 2 diabetes has examined the relationship between coffee consumption and CVD risk factors. This study suggests that higher coffee consumption is associated with lower fasting plasma glucose and diastolic blood pressure and higher high-density lipoprotein (HDL) cholesterol and triglyceride levels (107825). Population research has examined the relationship between coffee consumption and change in kidney function in patients with type 2 diabetes. One study in patients with normal kidney function suggests that drinking any coffee is associated with up to a 25% prevention in kidney function decline when compared with no coffee consumption. Kidney function decline was based on estimated glomerular function rate (eGFR) measurements (111043).
Heart failure. Consumption of caffeinated coffee seems to reduce the long-term risk of heart failure in those without cardiovascular disease (CVD) at baseline. Details: A meta-analysis of three large population studies, the Framingham Heart Study (FHS), Cardiovascular Heart Study (CHS), and Atherosclerosis Risk in Communities (ARIC) study, has found that increased daily coffee consumption is associated with a reduced long-term risk of heart failure in individuals without CVD at baseline. Drinking at least 2 cups of coffee daily is associated with a 29% to 31% reduced risk of heart failure. In the analysis, total caffeine intake, but not decaffeinated coffee intake, was associated with a reduced risk of heart failure (104597).
Overall mortality. Consumption of coffee seems to reduce all-cause mortality. The effects of coffee on specific causes of mortality are variable. Details: Population research conducted in almost 4 million international individuals suggests that long-term, daily consumption of coffee is associated with an 8% to 28% reduction in all-cause mortality when compared to low or no coffee consumption (97373,97374,103997,103998,104594,104595,105308,105311,105314,107826)(107833,107839,111033), though not all research agrees (107822). The strongest association is seen for individuals consuming 2-4 cups of coffee daily and in never smokers. Most research suggests that consuming ground, instant, or decaffeinated coffee is associated with similar reductions in mortality (97373,97374,103997,103998,104594,104595,105308,105311,105314,107833)(111033). The use of sweeteners might affect the association of coffee consumption with all-cause mortality. Population research suggests that consumption of unsweetened coffee, in amounts ranging from any to up to 4.5 cups daily depending on type of coffee, is associated with a reduction in mortality of 14% to 39% when compared with no coffee consumption. Consumption of 1.5 to 3.5 cups of sugar-sweetened coffee is associated with a reduction in mortality of approximately 30%; however, this association does not occur with higher coffee intakes or the consumption of decaffeinated coffee. Any association between the consumption of artificially sweetened coffee and mortality is unclear. When subgroup analyses were conducted to determine the association of coffee consumption with cause-specific mortality, coffee consumption was associated with a reduction in cardiovascular mortality. In some analyses, this association is for ground or decaffeinated, but not sweetened, instant, or unfiltered, coffee (97373,97374,103997,103998,104594,104595,105308,105311,105314,107833)(111032). In another analysis, consumption of coffee was inversely associated with deaths from chronic respiratory diseases, diabetes, pneumonia and influenza, and intentional self-harm. There were no associations between coffee consumption and deaths from accidents, Alzheimer disease, or kidney disease (105311). The association between coffee consumption and cancer-related mortality is less clear. Although one large meta-analysis of population research suggests that consumption of approximately 2 cups of coffee daily is associated with a 4% decrease in cancer-related mortality, the results of individual studies are mixed. One large population cohort suggests that ground or instant caffeinated coffee consumption is associated with up to a 27% reduction in cancer mortality (97374), while other analyses show no association (97373,103994,105308,105311,107822). The reasons for this discrepancy are not clear but may be related to smoking status or use of sweeteners. In one meta-analysis, consumption of each additional cup of coffee daily is associated with a 2% decrease in cancer-related mortality in non-smokers, as opposed to an increased risk in smokers (105308). Other population research suggests that only intake of unsweetened coffee, and not sugar-or artificially-sweetened coffee, is associated with a reduced risk of cancer-related mortality (111032).
Parkinson disease. Consumption of coffee seems to reduce the risk of developing Parkinson disease. This effect seems to be dose related in males, but not in females. Details: There is evidence that the risk of Parkinson disease is lower in people who consume caffeinated beverages such as coffee, tea, and cola. For males, the effect seems to be dose related. Males consuming the greatest amount of caffeinated coffee, 28 ounces (three to four cups) or a total of 421-2716 mg of caffeine from any source daily, seem to have the greatest reduction in risk. However, a significant reduction in risk exists even with consumption of as little as approximately 1-2 cups of coffee, or 124-208 mg of caffeine, daily (6022). In females, the effect does not seem to be dose related. Moderate consumption of caffeinated coffee, 1-3 cups daily, provides the greatest reduction in risk (1238). Coffee does not appear to provide additional protection from Parkinson disease in cigarette smokers (9236).
Postoperative bowel function. Consumption of coffee seems to decrease the time to first stool and first flatus, and possibly time to discharge, after gynecological or colorectal surgeries. Details: Meta-analyses of mainly small clinical trials in patients who have undergone gynecological or colorectal surgeries show that drinking coffee decreases the time to the first stool and time to tolerating solid food by about 10 hours when compared with no treatment or drinking water or tea (103991,111035). Although one meta-analysis found that drinking coffee does not reduce the length of hospital stay (103991), other research shows that hospital stay is reduced by up to 1.5 days; however, sub-analyses suggest that benefit is limited to gynecological surgery and not colorectal surgery or caesarian section (97386,111035). Sub-analyses show that drinking coffee does not improve bowel function after caesarian section (103991,111035). Caffeinated coffee has been most commonly consumed as 100 mL three times daily starting after surgery and until the first stool. Some studies have used decaffeinated coffee (93876,97386,103991,111035,111039).
Postoperative ileus. Consumption of coffee seems to reduce the risk of postoperative ileus. Details: A meta-analysis of mainly small clinical trials in patients who have undergone gynecological or colorectal surgeries shows that drinking coffee reduces the risk of postoperative ileus by 58% when compared with no treatment or drinking water or tea. Hospital length of stay was reduced by approximately 1.5 days. However, sub-analyses suggest that this benefit is limited to patients following cesarean section or gynecological surgery, and not colorectal surgery (111035).

POSSIBLY INEFFECTIVE

Esophageal cancer. Consumption of coffee does not seem to be associated with a reduced risk of esophageal cancer. Details: Population research has found that coffee intake is not associated with the incidence of esophageal cancer (9222,90186,100874). However, subgroup analyses have found coffee consumption may be associated with a reduced risk of esophageal cancer in patients from East Asia (100874).

INSUFFICIENT RELIABLE EVIDENCE to RATE

Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in consuming coffee for ADHD, there is insufficient reliable information about the clinical effects of coffee for this purpose.
Atherosclerosis. It is unclear if consuming coffee is beneficial for atherosclerosis. Details: Population research has found that drinking coffee is not associated with prevalent coronary-artery calcium, a subclinical marker of atherosclerosis, in patients without known coronary heart disease (97371).
Atrial fibrillation. It is unclear if consuming coffee affects the risk of atrial fibrillation. The available research is conflicting. Details: A meta-analysis of observational research suggests that coffee intake is not associated with the incidence of atrial fibrillation (100860). However, a more recent observational study suggests that drinking at least 1 cup of coffee per week is associated with a 40% increased risk of atrial fibrillation, with the highest incidence of atrial fibrillation occurring in adults consuming at least 6 cups daily. A sub-analysis found that this association remained only for White participants and not other ethnicities (111042). This study was limited by its relatively small sample size and a higher than general proportion of smokers. Some observational research in elderly persons following the Mediterranean diet suggests that consuming 4-28 cups of coffee monthly (up to 1 cup daily) is associated with a lower risk of atrial fibrillation when compared with 3 cups or less monthly. Consuming more than 1 cup of coffee daily was not associated with reduced risk (103988). However, it is unclear if this association was due to moderate coffee consumption, the Mediterranean diet, or other, unidentified factors.
Bladder cancer. Population research suggests that coffee consumption does not reduce the risk of bladder cancer. Details: Although earlier evidence has been conflicting (97375,97376), the most comprehensive analysis of cohort and case control studies has found that coffee consumption is not associated with bladder cancer risk. In subgroup analyses of females, males, or non-smokers, coffee did not affect risk (103992).
Brain tumor. It is unclear if consuming coffee reduces the risk of brain cancer. Details: Observational research has found that consumption of coffee is associated with a lower risk of brain cancer in Asian populations, but not in American populations (100870).
Breast cancer. Population research suggests that coffee consumption does not reduce the risk of breast cancer. Details: Population research has found that consumption of coffee is not associated with a reduced incidence of breast cancer (9235,97377,107823).
Cancer. Although there has been interest in using rectal coffee enemas for the treatment of cancer, there is insufficient reliable information about the clinical effects of coffee for this purpose.
Cardiovascular disease (CVD). Some population research has found that drinking coffee is associated with a reduced risk of heart failure, but not with a reduced risk of major adverse cardiac events, coronary heart disease, or CVD in general. In patients with a history of CVD, coffee consumption may reduce CVD-related mortality. However, at least some evidence suggests that there is a J-shaped association between coffee consumption and the risk of acute coronary syndromes. Details: A meta-analysis of three large population studies, the Framingham Heart Study (FHS), Cardiovascular Heart Study (CHS), and Atherosclerosis Risk in Communities (ARIC) study, suggests that increased daily coffee consumption is associated with a reduced long-term risk of heart failure in individuals without CVD at baseline. Drinking at least 2 cups of coffee daily is associated with a 29% to 31% reduced risk of heart failure. However, there was no association between coffee consumption and risk of stroke, coronary heart disease, or CVD in general. In the analysis, total caffeine intake, but not decaffeinated coffee intake, was associated with a reduced risk of heart failure (104597). In one cohort study, there was no association between past coffee-drinking and the prevalence of having coronary heart disease as determined by a coronary angiography (104588). However, a large population study suggests that drinking up to 5 cups daily of instant, ground, or decaffeinated coffee is associated with a reduced risk of incident CVD, including coronary heart disease, cardiac failure, and/or ischemic stroke, of approximately 11% (111033). The association between coffee consumption and arrhythmia has also been investigated. In one population study, there was a 3% reduced risk of arrhythmia for each additional cup of habitual coffee consumed. Similar effects were seen when atrial fibrillation and supraventricular tachycardia, but not ventricular tachycardia, were independently analyzed (105310). More recent population research suggests that consuming 1-5 cups daily of ground or instant coffee, but not decaffeinated coffee, is associated with up to a 17% reduced risk of arrhythmia when compared with not consuming coffee. Intake of more than 5 cups was no longer associated with a reduced risk of arrhythmia (111033). Some population research suggests a J-shaped association between regular coffee consumption and the risk of developing acute coronary syndromes. Moderate consumption of less than 300 mL daily (about 1.3 cups) was associated with a lower risk of developing acute coronary syndromes, whereas regular consumption of 300 mL daily or more was associated with an increased risk (11318). However, other population research in people without a history of CVD suggests that drinking more than 6 cups of coffee daily does not appear to be associated with an increased risk of developing coronary heart disease (14343). The association between coffee consumption and CVD-related mortality has also been evaluated in people with CVD. Population research suggests that coffee consumption is associated with a reduction in CVD-related mortality. In some analyses, this association is for ground or decaffeinated coffee only (97373,97374,103997,103998,104594,104595,105308,105311,105314). A meta-analysis of a small number of population studies suggests that consuming coffee for at least 1 year after a myocardial infarction (MI) is associated with a small reduction in risk of CVD-related mortality and no increased risk of all-cause mortality or major cardiac events, such as a recurrent MI or stroke (104882). In patients with a history of acute coronary syndrome, including acute MI or unstable angina, consumption of 1-3 cups of coffee daily is associated with a reduced risk of overall mortality over a 4-year period, especially in never or former smokers. However, in those who are current smokers, consuming more than 3 cups daily is associated with a more than 2-fold increased risk of overall mortality (8533,105313).
Chronic kidney disease (CKD). It is unclear if consuming coffee is beneficial for the prevention or management of CKD. Details: A small meta-analysis of population research has found that coffee consumption is associated with a 14% reduced incidence of CKD; drinking at least 2 cups daily seems to have the most benefit. Coffee consumption is also associated with an 18% reduced incidence of progression to kidney failure, as well as lower odds of having albuminuria. In addition, coffee consumption is associated with a reduced risk of CKD-related death, with at least 4 cups daily providing the most benefit when compared with drinking no coffee (104586). The validity of these findings is limited by the heterogeneous definitions of CKD, kidney failure, and albuminuria in the individual studies, as well as the comparisons of coffee consumption.
Cognitive function. It is unclear if consuming coffee is beneficial for cognitive function. Details: Some population research has found that higher lifetime coffee consumption might positively affect cognitive function among females aged 80 years or older (10620). Additionally, a small clinical study in healthy adults shows that consuming a single dose of regular coffee 220 mL containing 100 mg of caffeine improves reaction time and working memory, but not episodic memory, when compared with placebo (100864).
Colorectal cancer. It is unclear if consuming coffee is beneficial for the prevention or treatment of colorectal cancer. Details: A meta-analysis of cohort studies conducted in North America and Europe suggests that there is no association between coffee intake and the incidence of colorectal cancer (97385). However, population research conducted in Japan and Korea suggests that drinking coffee is associated with a lower risk of colorectal cancer, with the greatest reduction seen in patients consuming 3 or more cups of coffee daily (9222,97384,107832,111041). In one study, risk reduction increased from 32% to 78% when adjusted for the use of coffee additives, including cream and sugar (107832). In addition, drinking coffee is associated with a reduced risk of disease progression and death in patients with advanced or metastatic colorectal cancer. Each additional cup daily is associated with a 5% reduced risk of cancer progression and a 7% reduced risk of death. The greatest benefits were associated with drinking at least 4 cups daily when compared with no coffee consumption (104591).
Constipation. Although there has been interest in consuming coffee for constipation, there is insufficient reliable information about the clinical effects of coffee for this purpose.
Dementia. It is unclear if consuming coffee is beneficial for preventing dementia. Details: One meta-analysis of observational studies including nearly 329,000 adults has found that drinking coffee is not associated with a lower risk of dementia or Alzheimer disease (100866). Conversely, other observational research has found evidence of benefit, but results are conflicting. A meta-analysis of observational studies in nearly 334,000 adults has found a reduced risk of any cognitive deficit (including mild cognitive impairment and dementia) or dementia alone in those drinking less than 2.8 or 2.3 cups of coffee daily, respectively, when compared with not drinking coffee (107829). The validity of these findings is limited by a lack of discussion of heterogeneity and variability in sensitivity analyses. An individual observational study in nearly 14,000 adults has found that coffee and caffeine consumption is associated with dose-dependent reductions in dementia risk, especially in males, and that drinking at least 3 cups of coffee daily is associated with a 50% lower risk of dementia when compared with not drinking coffee (107841). Coffee consumption has also been studied in combination with tea. An observational study has found that drinking 0.5-1 cup of coffee with at least 4 cups of tea or 2-3 cups of coffee and tea each daily is associated with a 28% to 30% reduced risk of dementia when compared with not drinking coffee and tea (107204).
Depression. It is unclear if consuming coffee is beneficial for reducing the risk of depression. Details: Observational research has found that higher coffee consumption is associated with a 24% lower risk of depression when compared with lower coffee consumption. Drinking 400-600 mL of coffee daily is associated with 16% lower risk of depression when compared with not consuming coffee (100863).
Endometrial cancer. It is unclear if consuming coffee is beneficial for the prevention of endometrial cancer; the available research is conflicting. Details: One meta-analysis of prospective cohort studies suggests that drinking coffee is associated with a dose-dependent reduction in the risk of endometrial cancer. Increasing coffee consumption by 4 cups daily is associated with a 20% reduction in endometrial cancer risk (97381). Another meta-analysis of population research suggests that the highest intake of caffeinated coffee, but not decaffeinated coffee, is associated with a 34% reduced risk of endometrial cancer when compared with the lowest. A sub-analysis suggests that this association is limited to individuals with a high body mass index (111036). In contrast, earlier meta-analyses and one large prospective cohort study conducted in the United Kingdom suggests that drinking coffee is not associated with a reduced risk of endometrial cancer in general; however, there may be some protection in obese females drinking at least 2 cups of caffeinated coffee daily (93873,97381,97382).
Fractures. It is unclear if consuming coffee is beneficial for fracture prevention. Details: A meta-analysis of observational research suggests that the highest intake of coffee is not associated with a reduced odds of fracture when compared with the lowest. However, any association may be dependent on the dose of coffee and/or the location of research. A dose-response meta-analysis suggests that consuming 0.5 to 4 cups daily, but not higher amounts, is associated with a small reduction in the incidence of hip fracture when compared with no coffee consumption. Additional sub-analyses suggest that while the highest coffee consumption was associated with a 25% reduced risk of fracture in studies conducted in Europe and North America, the opposite is true in studies conducted in Asia where the risk is increased by 37% (111034).
Gallbladder disease. Population research suggests that consuming coffee may reduce the risk of developing symptomatic gallstone disease. Details: Population research has found that the consumption of caffeinated beverages, including coffee, that provide at least 400 mg of caffeine (two or more cups of coffee) daily is associated with a significantly reduced risk of developing symptomatic gallstone disease (3345,8032). The effect seems to be dose-dependent; consumption of 800 mg caffeine (four or more cups of coffee) daily is associated with the greatest reduction in risk (3345).
Gastric cancer. It is unclear if consuming coffee reduces the risk of gastric cancer. Details: Overall, meta-analyses of observational research suggest that coffee consumption does not affect gastric cancer risk. However, subgroup analyses of patients living in the United States suggest that consuming coffee is associated with an increased risk of gastric cancer (100873,111038). One sub-analysis suggests that consuming 6.5 or more cups of coffee daily was associated with a 36% greater risk of gastric cancer (100873).
Gout. It is unclear if consuming coffee is beneficial for preventing gout. Details: Epidemiological research has found that the risk of developing gout over a 12-year period is 40% lower in males aged 40-75 years who drink 4-5 cups of caffeinated coffee daily, compared with those who don't drink coffee. In people who drink 6 cups or more daily, the risk of developing gout is 59% lower. Drinking decaffeinated coffee is also associated with a reduced risk of developing gout, but the risk reduction is more modest than with caffeinated coffee (15540).
Headache. Although caffeine is an established treatment for certain types of headache, there is insufficient reliable information about the clinical effects of coffee, specifically, for this purpose.
Hearing loss. It is unclear if consuming coffee is beneficial for hearing loss. Details: Population research has found that consuming at least one cup of coffee daily is associated with a reduced risk of hearing impairment in males, but not females, when compared with less than one cup of coffee daily. In males, each additional cup consumed daily was associated with a 15% lower risk of hearing impairment (104592).
Hepatitis B. It is unclear if consuming coffee is beneficial for hepatitis B. Details: Population research in patients being treated for chronic hepatitis B suggests that drinking at least 3 cups of coffee a day is associated with a reduced risk of having liver fibrosis when compared to not consuming coffee. However, this association was not present in untreated patients (111044). This study is limited by its cross-sectional design and use of blood markers, rather than the gold standard liver biopsy, for diagnosing fibrosis.
Hyperlipidemia. It is unclear if consuming caffeinated coffee is beneficial for hyperlipidemia. Details: A meta-analysis of small, randomized, controlled trials shows that consuming caffeinated coffee for up to about 11 weeks reduces total cholesterol by 8 mg/dL, low-density lipoprotein (LDL) cholesterol by 5 mg/dL, and triglycerides by 13 mg/dL when compared with a control group. These effects appear to be dose-dependent, with the greatest reduction observed in individuals consuming 6-8 cups of coffee daily. Every additional cup of caffeinated coffee consumed daily is associated with a 3-4 mg/dL additional reduction in total and LDL cholesterol and a 6-7 mg/dL additional reduction in triglyceride levels. Decaffeinated coffee had no effect on any markers of cholesterol (97370). However, population research has found that coffee consumption is associated with slightly higher total cholesterol, LDL cholesterol, and triglyceride levels when compared with no coffee consumption (104590).
Hypertension. Epidemiologic research suggests that consuming coffee reduces the risk of developing hypertension. Details: Some epidemiological research suggests that coffee consumption might reduce the risk of developing hypertension. A meta-analysis of epidemiologic research suggests that long-term coffee intake is associated with a modest 9% reduction in the risk of developing hypertension. However, smoking may diminish any potential benefit (97372). This analysis did not investigate the likelihood of a dose-response relationship and did not adjust for smoking status. Another epidemiologic study in a Brazilian population that did adjust for sociodemographic factors such as smoking suggests that drinking 1-3 cups of coffee daily is associated with a reduced risk of hypertension by about 18% when compared with never or almost never drinking coffee. Drinking more than 3 cups of coffee did not impact risk (103993). However, this study defined 1 cup of coffee as 50 mL; it is unclear how this intake compares with typical use in other countries. The best evidence comes from a meta-analysis of observational research which suggests that coffee intake was not associated with hypertension risk. However, coffee intake was associated with a modest reduction in hypertension risk in studies conducted in the United States (111037). In patients with hypertension, a meta-analysis of epidemiologic research suggests that habitual coffee intake is not associated with the risk of developing CVD (105312). However, other prospective population research in patients with severe hypertension, but not mild hypertension, suggests that drinking at least two cups of coffee daily is associated with a 2-fold increase in CVD mortality compared with non-coffee drinkers (111027).
Hypotension. It is unclear if consuming caffeinated coffee is beneficial in older adults with postprandial hypotension. Details: Preliminary clinical research in older adults with postprandial hypotension shows that consuming caffeinated beverages like coffee seems to increase blood pressure (11835).
Kidney failure. It is unclear if consuming coffee is beneficial for preventing progression to kidney failure or reducing the risk of chronic kidney disease (CKD)-related death. Details: A small meta-analysis of population research has found that coffee consumption is associated with an 18% reduced incidence of progression from CKD to kidney failure. Coffee consumption is also associated with a reduced risk of CKD-related death, with at least 4 cups daily providing the most benefit when compared with not drinking coffee (104586). This analysis is limited by the heterogeneous definitions of CKD and kidney failure in the individual studies, as well as the comparisons of coffee consumption.
Liver cancer. It is unclear if consuming coffee reduces the risk of liver cancer. Details: A meta-analysis of observational research in approximately 2.5 million adults in Asia, North America, and Europe suggests that consuming at least 1 cup of coffee daily is associated with a 27% to 48% reduced risk of liver cancer (111016). An earlier meta-analysis of observational research suggests that regular coffee consumption is associated with a 31% lower risk of hepatocellular carcinoma when compared with no consumption. Higher coffee consumption seems to have a greater preventative effect when compared with lower coffee consumption (103989).
Liver disease. It is unclear if consuming coffee reduces the risk of chronic liver disease. Details: Observational research has found that regular coffee consumption is associated with a 38% lower risk of chronic liver disease when compared with no consumption. Higher coffee consumption seems to have a greater preventative effect when compared with lower coffee consumption (100862).
Lung cancer. It is unclear if consuming caffeinated coffee reduces the risk of lung cancer; the available research is conflicting. Details: Epidemiological research has found that males who consume a higher amount of dietary phytoestrogens, such as the lignan precursors found in coffee and tea, have up to a 27% lower risk of developing lung cancer when compared with those who consume smaller amounts (13190). However, conflicting evidence suggests that people who consume 2-4 or more cups of caffeinated coffee daily have a significantly increased risk of developing lung cancer (13191,90177). But drinking decaffeinated coffee seems to be associated with a decreased risk of lung cancer (13191).
Melanoma. It is unclear if consuming coffee reduces the risk of malignant melanoma. Details: Population research has found that high coffee intake is associated with a 19% to 25% reduction in the risk of malignant melanoma when compared with low consumption. However, after adjusting for confounders, most data show no significant reduction. Drinking decaffeinated coffee is not associated with a reduced incidence of malignant melanoma (97378,97379).
Metabolic syndrome. It unclear if consuming decaffeinated coffee is beneficial in patients with metabolic syndrome. Details: A meta-analysis of mostly small randomized controlled studies in patients with metabolic syndrome shows that consumption of decaffeinated coffee modestly reduces systolic and diastolic blood pressure when compared with control. The validity of these findings is limited by the high heterogeneity and small size of the included studies (107830).
Nonalcoholic fatty liver disease (NAFLD). Observational research suggests that consuming coffee may reduce the risk of NAFLD. Observational and clinical research on liver fibrosis is conflicting. Details: A meta-analysis of observational research in over 50,000 patients has found that drinking 1-2 cups of coffee daily does not affect NAFLD incidence when compared with drinking less than 1 cup of coffee. However, drinking more than 3 cups of coffee daily was associated with a reduced risk of NAFLD when compared with less than 2 cups daily (103990). Other observational research has found a reduced risk of NAFLD and/or fibrosis in those who drink coffee when compared with those who do not drink coffee (100872,107831). However, the validity of these findings is limited by a relatively small population size and the lack of dose-response analyses. Two of the primary bioactive constituents of coffee, caffeine and chlorogenic acid, also have been evaluated. A small study in patients with NAFLD and type 2 diabetes shows that taking caffeine 200 mg and/or chlorogenic acid 200 mg for 6 months has no effect on the reduction of hepatic fat and fibrosis when compared with placebo (107835).
Nonmelanoma skin cancer. It is unclear if consuming caffeinated coffee reduces the risk of nonmelanoma skin cancer. Details: Population research has found that the highest intake of coffee or caffeine is associated with an 18% reduction in nonmelanoma skin cancer risk when compared with the lowest intake. However, the benefit appears to be limited to the incidence of basal cell carcinoma. Drinking decaffeinated coffee is not associated with a reduced incidence of nonmelanoma skin cancer. The effect, if any, appears to be due to caffeine rather than coffee (97380).
Obesity. It is unclear if consuming coffee is beneficial for weight loss in patients who are overweight or obese; the available research is conflicting. Details: Some clinical research in males who are overweight or obese and are receiving dietary counseling shows that taking coffee mannooligosaccharides 2 grams twice daily for 12 weeks reduces body weight by 6%, compared with 2.3% with placebo. The product also reduces body fat in males, but not females (93877). Additional clinical research in patients with pre-obesity shows that drinking a dark roast coffee 500 mL daily, enriched with N-methylpyridinium ions, for 4 weeks results in weight loss of 3.5%, compared with 0% with a light roast coffee enriched in chlorogenic acids. The dark roast coffee appears to reduce caloric intake (93874). However, other clinical research in adults who are overweight or obese shows that drinking caffeinated or decaffeinated coffee 885 mL daily for 8 weeks does not appear to improve glycemic control or reduce weight (93879).
Osteoporosis. It is unclear if consuming coffee is beneficial for osteoporosis prevention. Details: A meta-analysis of observational research suggests that the highest coffee consumption is associated with a 21% reduced odds of osteoporosis when compared with the lowest (111034).
Pancreatitis. It is unclear if consuming coffee reduces the risk of pancreatitis. Details: Observational research has found that drinking three or more cups of coffee daily is associated with a 22% lower risk of pancreatitis when compared with drinking less coffee (100871).
Pharyngeal cancer. It is unclear if consuming coffee reduces the risk of pharyngeal cancer. Details: Observational research has found that high coffee consumption is associated with a 28% reduced odds of pharyngeal cancer when compared with low coffee consumption (100869).
Pregnancy-induced hypertension. It is unclear if consuming coffee reduces the risk of pregnancy-induced hypertension. Details: A large prospective cohort study in pregnant patients in Japan has found that the highest total caffeine intake is associated with a 26% increased risk of pregnancy-induced hypertension when compared with no intake, but that a higher coffee intake (at least 2 cups daily) is associated with a 21% reduced risk of pregnancy-induced hypertension when compared with no intake, even when adjusted for total caffeine intake (107827). The validity of these findings may be limited by the fact that detailed information on proteinuria and hypertension were unavailable.
Pneumonia. It is unclear if consuming coffee is beneficial for reducing the risk of pneumonia. Details: A case-control study in elderly patients has found a 50% reduced risk of pneumonia in those consuming 2 or more cups of coffee daily over the past month (107840). The validity of this finding may be limited by differences in the baseline characteristics between the matched control subjects and the cases, specifically the higher prevalence of hypertension and diabetes in the control group.
Prostate cancer. Population research has found that coffee consumption is associated with a modestly reduced risk of prostate cancer. Details: Although some individual studies disagree (107834), population research has found that the highest coffee consumption is associated with a small reduction in the risk of prostate cancer when compared with the lowest consumption (97383,97384,104587). Sub-analyses show that coffee consumption is associated with a 7% reduced risk of localized, but not advanced or fatal, prostate cancer (97383,97384,104587).
Stroke. It is unclear if coffee consumption, alone or in combination with tea, is beneficial for stroke, post-stroke dementia, all-cause mortality, or stroke-related mortality. The available research is conflicting. Details: Several meta-analyses of population research in patients with and without cardiovascular disease (CVD) have found no association between coffee consumption and risk of stroke (104597,104882). However, another meta-analysis of population research and an individual observational study have found that coffee consumption (e.g., 2-3 cups of coffee daily) is associated with an 8% to 12% reduced risk of stroke, especially ischemic stroke, when compared with no consumption (107204,107828). The validity of the findings from the meta-analysis is limited by the lack of a dose-response analysis. Additionally, this analysis found that consumption of 2-3 cups of coffee daily is associated with a 20% reduced risk of post-stroke dementia when compared with not drinking coffee (107204). The consumption of coffee in combination with tea has also been evaluated. An observational study has found that consumption of 2-3 cups daily each of coffee and tea, including black tea, is associated with a 32% reduced risk of stroke when compared with not drinking coffee and tea. Additionally, consumption of 0.5-1 cup of coffee and 2-3 cups of tea, including black tea, daily is associated with a 50% reduced risk of post-stroke dementia when compared with not drinking coffee and tea (107204). Coffee consumption has also been evaluated for its effects on stroke-related and all-cause mortality. One observational study has found that consumption of 1-2 cups of coffee daily is associated with a 50% reduced risk of stroke-related mortality (107822). However, another observational study in patients with a history of stroke has found no association between coffee consumption and all-cause mortality (107839).
Thyroid cancer. It is unclear if consuming coffee reduces the risk of thyroid cancer. Details: Population research has found that high coffee consumption is associated with a 25% lower risk of thyroid cancer when compared with low consumption. Every additional cup of coffee was associated with a 5% reduction in risk (103996). More evidence is needed to rate coffee for these uses.

(Read more about COFFEE)

SOY (Isoflavone, Soy Protein)

POSSIBLY EFFECTIVE

Breast cancer. High dietary intake of soy might be beneficial for the prevention of breast cancer and breast cancer recurrence in some patients. However, soy supplements do not seem to be beneficial. Details: For prevention, most population research has found that higher dietary intake of soy is associated with up to a 26% reduced odds of developing breast cancer when compared with a lower intake (7335,7336,11038,11807,75377,75587,90955,108251). One meta-analysis of population research found that patients who consumed more than 15 mg soy isoflavones daily made up about 25% of all cases of breast cancer, compared with 75% of cases in the group of patients consuming less than 15 mg daily (108251). The effects appear to vary depending on the ethnicity of the patient. Population research has consistently found that a high-soy diet in Asian and Asian-American females is associated with a significantly reduced risk of breast cancer (7335,7336,11038,11807,75377,75587,90955). However, the amount of soy consumed in a Western diet, even among those who consume the highest amounts of soy, was not found to have a preventative effect (11391,17109,90955,90967). The reason for the disparate findings are unknown but may be related to genetic differences or differences in quantification of soy intake (7663,94153). Also, the prophylactic benefit seems to apply regardless of whether high amounts of soy are consumed during adolescence or later in life (7335,7336,9674). Limited population research has also found that consuming a diet high in soy is associated with up to a 25% reduced risk of breast cancer recurrence; however, it is unclear whether there is an association with reduced mortality in breast cancer patients (90956,90969,94154). The effect appears to be greater for certain subgroups of breast cancer patients. Increased dietary soy intake is associated with a 28% to 36% risk reduction in patients with estrogen receptor (ER)-negative tumors, a 30% risk reduction in patients with ER-positive/progesterone receptor (PR)-positive tumors, and a 25% to 36% risk reduction in postmenopausal patients (90956). Some small clinical studies have also evaluated the use of soy isoflavone extract . One small clinical study in patients with breast cancer shows that taking a soy isoflavone extract 200 mg daily for 2 weeks prior to surgery does not seem to affect cancer cell growth when compared with a historical control (11042). Another small clinical study in patients at high risk for breast cancer or with a history of breast cancer shows that taking a soy tablet containing 50 mg soy isoflavones (Novasoy, Archer Daniels Midland Co.) daily for 12 months does not alter mammographic or breast tissue density when compared with placebo (95999).
Chronic kidney disease (CKD). Oral soy protein seems to improve some measures of disease severity in patients with CKD. Details: Clinical research shows that consuming soy protein seems to reduce proteinuria in people with kidney disease (2286,2287,2288,75249,75634). Also, a meta-analysis of clinical research in patients with CKD who are not on dialysis shows that soy protein intake reduces serum levels of creatinine by 0.07 mg/dL, phosphorus by 2.5 mg/dL, and triglyceride by 18 mg/dL when compared with placebo or control (90989).
Diabetes. Diets high in soy seem to reduce the risk of type 2 diabetes. Also, oral soy protein, but not soy isoflavones, seems to modestly improve glycemic indices. It is unclear if soy is beneficial for lowering blood lipid levels or reducing cardiovascular (CVD) mortality risk in adults with type 2 diabetes. Details: A meta-analysis of observational studies has found that higher dietary intake of tofu, soy protein, or soy isoflavones is associated with an 8% to 16% lower risk of developing diabetes when compared with a lower dietary intake (105608). In menopausal patients without diabetes, a meta-analysis of clinical research shows that intake of soy isoflavones 40-161 mg daily seems to improve glycemic indices when compared with control (96423). Some research shows that soy can modestly improve glycemic indices in patients with diabetes. A meta-analysis of small low-quality clinical studies in patients with diabetes or metabolic syndrome shows that taking various formulations of soy protein modestly reduces fasting plasma glucose and insulin levels, as well as insulin resistance, when compared with control (96001). An older meta-analysis assessing both healthy patients and patients with diabetes shows that a whole soy diet reduces fasting blood glucose by about 4 mg/dL when compared with control (75493). Small clinical studies also suggest that an extract of the fermented soybean product, Touchi, acts as an alpha-glucosidase inhibitor. It seems to modestly lower blood glucose, glycated hemoglobin (HbA1c), and triglycerides in patients with type 2 diabetes (11762,75205). However, some conflicting evidence exists. A meta-analysis of small, low-quality clinical studies in patients with type 2 diabetes shows that taking soy isoflavones does not improve glycemic indices when compared with control (105610). Also, another meta-analysis of clinical research in patients with type 2 diabetes shows that taking soy protein and/or soy isoflavones for 6-12 weeks does not improve glycemic indices when compared with either soy protein without isoflavones, other protein, or placebo (105610). Reasons for these conflicting results are unclear but may relate to differences in baseline blood glucose levels, the formulation of soy, or the duration of treatment. Some research shows that soy may modestly improve the lipid profile in patients with diabetes. A meta-analysis of clinical research in patients with diabetes shows that taking soy protein and/or soy isoflavones for 6-12 weeks modestly reduces levels of total and low-density lipoprotein (LDL) cholesterol, but not high-density lipoprotein (HDL) cholesterol or triglycerides, when compared with control (105610). Consuming soy foods might reduce the risk of mortality related to CVD in patients with diabetes. Population research suggests that consuming soy foods at least four days each week is associated with a 23% reduced risk of CVD mortality when compared with never consuming soy foods. Consuming soy foods less than four times weekly is not associated with CVD mortality risk (108242). Soy is also of interest in the prevention or treatment of gestational diabetes. Population research has found that consumption of less than 40 grams of soy daily in the second trimester is associated with a 2.1-fold increased risk of gestational diabetes when compared with daily soy intake of 40 grams or more (108241). Also, a small clinical trial in patients with gestational diabetes shows that consuming a diet containing about 0.3 grams/kg soy protein for 6 weeks, beginning at 24-28 weeks' gestation, reduces blood glucose levels, insulin resistance, and triglyceride levels when compared with consuming a non-soy control diet (95993).
Diarrhea. Oral soy fiber seems to reduce acute diarrhea in infants, although it may not be beneficial in adults. Details: Giving soy fiber-supplemented formula orally, either alone or in combination with oral rehydration solution, seems to reduce the duration of acute diarrhea in infants when compared with cow's milk formula or oral rehydration solution alone (2291,2292,75474,75517,75523,75531,75572). However, in some studies, a reduction in the duration of acute diarrhea was not observed when compared with cow's milk formula (75522,75542). In adult patients receiving nutrition via intubation, preliminary clinical research suggests that treatment with soy-polysaccharide fiber does not improve the incidence of diarrhea when compared to control (75508).
Galactosemia. Oral soy protein can be used in infant formula to prevent symptoms of galactosemia. Details: Soy does not contain the sugar galactose. Some research suggests that giving oral isolated soy protein-based formula in place of milk-based formula to infants seems to be helpful for preventing symptoms of galactosemia (3400).
Hyperlipidemia. Oral soy protein seems to modestly reduce lipid levels. However, purified soy isoflavone may not have the same benefit. Details: Consuming soy protein orally, in place of other dietary protein, seems to modestly reduce total cholesterol and low-density lipoprotein (LDL) cholesterol by about 3% to 4% when compared with control (842,2293,2294,2296,2585,3402,4755,6412,7346,7803)(8530,10459,42059,75356,105598,105604). Additionally, some research shows that soy protein might be more effective in patients with more severe hyperlipidemia (75497). The FDA has approved labeling for specific soy products that states that they may be used for cholesterol reduction in combination with a diet low in saturated fat and cholesterol. To be eligible for this labeling, soy products must provide at least 6.25 grams of soy protein per serving, which is 25% of the effective daily intake (3977). However, not all evidence is positive. Some studies have shown no benefit of soy protein or isoflavones on LDL cholesterol levels when compared to control (8521,9679,12034,17105,53771,75236)(75242,75274,75276). Furthermore, although a few clinical trials have shown significant decreases in triglycerides following supplementation with soy or soy protein isolate (75258,75365), most studies suggest that soy protein does not decrease triglycerides when compared to control (2293,6412,8530,12034,17105). The effect of soy protein on high-density lipoprotein (HDL) cholesterol is inconsistent. Most studies suggest that it does not increase HDL levels (2293,6412,8530,12034,75286)(75524), although some analyses of clinical research suggest that soy might increase HDL cholesterol levels by up to 4% when compared to control (75480,75497). Doses of soy protein have ranged from 25-135 grams daily, providing 40-318 mg daily of isoflavones; however, higher doses do not seem to be more effective (17106,105598). Some evidence suggests that soy protein providing more isoflavones, or supplemented with isoflavones, might be more effective (3402,6413,10459), but this has not been consistently found in studies (3402). Most studies evaluating soy protein products containing little to no isoflavones suggest that these products are not effective (3402,7346,9679); however, purified soy isoflavone supplements alone do not seem to decrease LDL cholesterol (851,4738,7345,8502,10459,14066). In addition to soy protein, limited evidence suggests that soy fiber alone might reduce total cholesterol, LDL cholesterol, and triglyceride levels when compared with placebo (75686,75689). There is also some evidence that ultra-high temperature (UHT) treatment of soy milk destroys any cholesterol-lowering activity (17106).
Hypertension. Oral soy seems to modestly reduce blood pressure in some patients. Details: A meta-analysis of the available clinical research shows that consuming soy products modestly lowers systolic and diastolic blood pressure by an average of 1.6 mmHg and 1.2 mmHg, respectively, when compared with control (105605). This analysis is limited by high risk of bias and the lack of a dose-response relationship. An older meta-analysis, as well as individual clinical studies, in patients with prehypertension or mild hypertension show that consuming soy protein 18-40 grams, providing 118-143 mg of isoflavones, daily or black soy peptide 4.5 grams daily for 8 weeks reduces systolic blood pressure by about 4-8 mmHg and diastolic blood pressure by about 3-5 mmHg when compared with control (1313990962,90965). In normotensive patients, soy protein does not seem to reduce systolic or diastolic blood pressure (90965).
Lactose intolerance. Oral soy protein can be used in infant formula to prevent symptoms of lactose intolerance. Details: Providing isolated soy protein-based formula orally to infants is an acceptable alternative to milk-based formulas, especially for infants with symptoms of lactose intolerance (3400).
Menopausal symptoms. Oral soy seems to reduce hot flashes in patients with menopausal symptoms. Details: Consuming soy protein 15-60 grams, providing 34-100 mg of isoflavones, daily seems to modestly decrease the frequency and severity of hot flashes in some menopausal adults. Improvement seems to be greater in those with a higher frequency of hot flashes at baseline (2296,2297,3978,3986,3987,7653,9917,11805,15220,17110,75478)(75486,75649,92661,95997). Taking concentrated soy isoflavone extracts, providing 35-200 mg of isoflavones, daily seems to have similar effects (4751,6455,7802,9916,10460,11805,11993,11994,13209,15220)(15850,75478,90950,90979,92661). Higher doses of 100-200 mg of isoflavones daily and higher frequency of dosing intervals seem to have greater benefit (90950). Furthermore, the amount of the specific isoflavone genistein contained in a soy product may influence outcomes. According to one analysis, studies using products that provide at least 15 mg of genistein daily consistently show positive outcomes. Studies using products containing a lower concentration of genistein have produced inconsistent findings (15133). Not all research has found that soy extracts reduce hot flashes (7801,11806,14062,15038,15851,16762); some experts speculate that this is due to a high placebo response (9916). Some clinical research has compared soy isoflavone extracts to conventional estrogen replacement. In one study, a concentrated soy isoflavone extract of genistein 54 mg daily reduced hot flashes by 22% to 29%, compared to 54% in those taking 17beta-estradiol as 1 mg daily plus norethisterone acetate 0.5 mg daily (11994). Additional preliminary research suggests that taking a soy isoflavone extract providing 60 mg isoflavones twice daily is comparable in efficacy to conjugated estrogens 0.625 daily for reducing menopausal symptoms. Conjugated estrogens seem to work more quickly; it seems to take up to 2 months to achieve the full effect of soy isoflavones (13209). One clinical trial compared soy isoflavones 10-40 mg daily to S-equol, a soy isoflavone metabolite. Soy isoflavones were less effective for reducing hot flash frequency when compared with S-equol (90960). This has led to some speculation that the effectiveness of soy in relieving hot flashes is influenced by a patient's ability to convert daidzen, a soy isoflavone, to S-equol (90950). It is theorized that patients who are S-equol producers are more likely to achieve symptom relief from soy. However, observational and clinical research does not support this theory (90990,94162). Soy has also been evaluated for the management of other symptoms of menopause. Some clinical research in menopausal patients with depression suggests that taking soy 100 mg, providing 50 mg of soy isoflavones, in combination with sertraline 50 mg daily for three months improves depression severity when compared with sertraline or soy alone (90958). An analysis of two small clinical trials shows that supplemental soy providing 50-118 mg of isoflavones can reduce vaginal dryness scores by 0.26 when compared with control (92661). Also, an open-label study suggests that drinking a specific beverage (ViveSoy) containing soy protein 15 grams and soy isoflavones 50 mg orally daily for 12 weeks reduces overall urogenital symptoms when compared with a control group (95997). However, one small clinical study in perimenopausal patients shows that a soy-rich diet does not relieve urogenital symptoms, including vaginal dryness, itching, and urinary incontinence, when compared with a soy-free diet (75285).
Metabolic syndrome. Oral soy protein seems to improve glycemic control and other markers of metabolic syndrome. Details: A meta-analysis of clinical research in patients with diabetes or metabolic syndrome shows that following a diet high in soy protein can decrease fasting plasma glucose and insulin levels, as well as insulin resistance, when compared with a control diet. Furthermore, dietary intake of soy protein modestly decreases diastolic blood pressure and low-density lipoprotein (LDL) cholesterol by a small amount in this population, although there is no effect on systolic blood pressure, high-density lipoprotein (HDL) cholesterol, or triglycerides (96001). Other clinical research shows that consuming a soy nut diet or a soy protein diet reduces fasting plasma glucose and LDL cholesterol levels when compared to baseline in postmenopausal adults with metabolic syndrome; however, the soy nut diet seems to more beneficial than either the soy protein diet or a Dietary Approaches to Stop Hypertension (DASH) diet (75378).
Muscle strength. Oral soy protein seems to increase muscle strength. Details: Overall, soy protein combined with resistance training seems to increase muscle strength when compared with placebo (16748,75246,96942,98871). A meta-analysis of three clinical studies shows that consuming soy protein in addition to resistance training improves strength and lean body mass in untrained athletes (98871). Other clinical research shows that soy also improves muscle strength in trained athletes and postmenopausal adults (75246,96942). One study in Olympic endurance athletes shows that consuming isolated soy protein (Supro) 1.5 grams/kg daily for 8 weeks increases body mass and strength indices and reduces fatigue when compared with no protein supplementation (75246). Clinical research in postmenopausal adults undergoing resistance training 3 days weekly shows that taking soy protein 25 grams daily in skim milk for 16 weeks increases the maximum amount of weight lifted in one repetition by over 80% for both bench press and knee extension when compared to a maltodextrin placebo (96942). Soy protein has also been compared with other protein supplements. A meta-analysis of preliminary clinical studies and other clinical research show that soy protein seems to work as well as whey, beef, and dairy (casein and whey) protein for improving muscle strength (75404,85941,98871,105591). However, the validity of these findings is limited by the small size and high heterogeneity of the studies.
Osteoporosis. Oral soy isoflavones seem to improve bone density and reduce the risk of osteoporosis in post-menopausal adults. Details: Most clinical research suggests that soy protein or soy extract containing 75-90 mg of isoflavones can increase bone mineral density (BMD), or slow BMD loss, and improve biochemical markers of bone turnover in peri- and postmenopausal adults when compared with control (842,4951,6449,9775,11082,90972,90980). Lower doses of isoflavones do not seem to be as beneficial. However, some observational research in postmenopausal Japanese adults and Chinese females aged 30-40 years has found that consuming about 50 mg dietary soy isoflavones daily is associated with a higher BMD when compared with lower soy isoflavone intake (7342,11081). An observational study in postmenopausal Asian patients has found that consuming higher dietary soy protein is associated with a lower risk of developing fractures when compared with lower amounts (13181). However, not all research has been positive. Some conflicting evidence suggests that soy protein does not improve BMD in some postmenopausal adults. The discrepancy in findings may be due to differences in soy formulations, concomitant treatments, or variable patient populations (4952,12034,14064,90978). For example, most evidence shows that soy does not affect BMD in premenopausal patients or bone turnover in adolescents (7660,8532,9684,11086). It is theorized that only people who can convert daidzein, a soy isoflavone, to S-equol might obtain benefits from soy (4952). However, clinical research suggests that there is no difference in bone calcium retention between equol producers and nonproducers (95995).

POSSIBLY INEFFECTIVE

Benign prostatic hyperplasia (BPH). Oral soy does not seem to reduce BPH symptoms. Details: Clinical research in patients with BPH shows that taking soy isoflavones 40 mg (Soylife 40, Acatris) daily for 12 months does not improve peak urine flow rate, residual urine volume, symptoms of BPH, or general quality of life when compared with placebo (90983).
Breast cancer-related hot flashes. Oral soy does not seem to reduce the risk for breast cancer-related hot flashes. Details: Clinical research shows that consuming a soy beverage providing soy isoflavones 90 mg daily or taking a soy extract providing soy isoflavones 50 mg three times daily does not reduce hot flashes in breast cancer survivors (3991,7658,8499). Observational research in breast cancer survivors has also found no association between hot flash incidence and soy isoflavone consumption (105602).
Colorectal cancer. Oral soy does not seem to reduce the risk for colorectal cancer. Details: Some observational research from China and Japan has found that intake of soy protein or soy isoflavone is not associated with the risk of developing colorectal cancer (105601). Furthermore, some clinical research shows that soy protein powder 58 grams containing isoflavones 83 mg, taken daily for 12 months, does not reduce the proliferation of colorectal epithelial cells in patients with adenomatous polyps when compared to control (75282).
Exercise-induced muscle soreness. Oral soy does not seem to reduce muscle soreness after exercise. Details: Some clinical research shows that taking soy isoflavone extract 120 mg orally for 30 days prior to exercise doesn't ameliorate muscle soreness caused by exercise when compared with placebo (8524).

INSUFFICIENT RELIABLE EVIDENCE to RATE

Alzheimer disease. It is unclear if oral soy improves cognition in patients with Alzheimer disease. Details: Preliminary clinical research in patients with Alzheimer disease shows that taking soy isoflavones (Novasoy, Archer Daniels Midland Co.) 100 mg daily for 6 months does not improve cognition when compared with placebo (96424).
Androgen deprivation therapy (ADT)-associated hot flashes. One small clinical study in patients with prostate cancer receiving ADT shows that taking soy protein powder 20 grams, providing 160 mg of isoflavones, alone or along with venlafaxine 75 mg, once daily for 12 weeks does not improve the severity of hot flash symptoms when compared with milk protein, with or without venlafaxine (90981).
Asthma. It is unclear if oral soy reduces asthma symptoms. Details: One population study has found that people with asthma who consume soy foods providing more than 250 mcg of genistein for every 1000 kcal consumed (e.g., 500 mcg/day for 2000 kcal diet) daily have increased lung function, as measured by FEV1 scores, when compared to those who consume less (11084). However, clinical research in adult and pediatric patients with poorly controlled asthma shows that taking soy isoflavones 50 mg twice daily for 24 weeks does not improve FEV1 scores, reduce the number of asthma episodes, or improve asthma symptoms when compared with placebo (90977).
Cardiovascular disease (CVD). It is unclear if soy consumption reduces the risk for CVD or CVD-related mortality. More research is needed to determine whether certain populations may benefit from increased soy intake. Details: Due to mixed findings, it is unclear if consuming soy is associated with a reduced risk of CVD events. One population study has found that consuming at least 60 grams of soy daily over a 12-month period is associated with a 14% reduced risk of having a CVD event over the next 5 years, as well as a reduced risk of stroke, when compared with consuming less than 15 grams daily (108253). A study in Japan has found that consuming soy five or more times per week over a 10-year period is associated with fewer adverse cardiovascular outcomes in only a certain subset of patients when compared with consuming soy twice a week or less. Postmenopausal adults with the highest consumption had a 36% lower risk of stroke, a 45% lower risk of myocardial infarction, and a 65% lower risk of CVD mortality. However, risk was not significantly reduced in males or premenopausal adults (17108). In contrast, a study in Korea has found that consuming a median of 16.5 servings of soy per week is associated with a 64% reduced risk of CVD incidence in premenopausal, but not postmenopausal, adults when compared with a median of 4.7 servings per week. A subgroup analysis has found that the highest intake of tofu, but not soybeans, fermented soy paste, or soy milk, is associated with a reduced incidence of CVD (108243). Additionally, higher dietary intake of soy does not seem to be associated with a reduced risk of cardiovascular events in Western females (13040). The amount of phytoestrogens typically consumed in Western diets is significantly lower than the amount typically consumed in Asian diets. The form of soy food and isoflavone content might play a role in these discrepancies. Any association between consumption of soy-containing foods and CVD mortality is also unclear. A meta-analysis of observational studies conducted in China or Japan has found that the highest intake of soy-containing foods is not associated with a lower risk of CVD-related mortality when compared with the lowest intake (96941). A population study in patients with or without a prior history of CVD has also found that soy-containing food consumption is not associated with a lower risk of CVD-related mortality when compared with the lowest intake (108244). However, some research has found a positive effect of soy consumption on CVD mortality risk. A subgroup analysis of a meta-analysis has found that the highest intake of fermented soy products is associated with a 16% reduced risk of CVD mortality; higher intake of non-fermented soy is not associated with CVD mortality (96941). Population research in patients without a prior history of CVD has found that soy-containing food consumption is associated with a lower risk of myocardial infarction-related mortality when compared with the lowest intake (108244). Also, one population study in adults with type 2 diabetes has found that consuming soy-containing foods at least four days each week is associated with a 23% reduced risk of CVD mortality when compared with never consuming soy foods. Consuming soy foods less than four times weekly is not associated with CVD-related mortality (108242).
Cervical cancer. It is unclear if oral soy reduces the risk for cervical cancer. Details: Population research has found that the highest dietary intake of soy over approximately 17 years is associated with a 57% decreased risk of cervical cancer when compared to the lowest intake of soy in females who also drank green tea. However, neither soy intake nor green tea intake alone was associated with a decreased risk of cervical cancer. Additionally, other population research has not confirmed an association between soy intake and cervical cancer (101800).
Child growth. It is unclear if oral soy protein enhances child growth. Details: Preliminary clinical research in Colombian children 2-7 years of age shows that consuming a soy protein supplement dissolved in fruit juice on 6 days of every week for 1 year does not improve body mass index, body composition, weight, or height when compared with consuming fruit juice and whole milk. A sub-analysis shows that children consuming the soy protein supplement had an increase in weight-for-age when compared with the control group, indicating that the supplement may be beneficial for ensuring adequate weight and nutritional status during prepubertal growth (100320). However, the children in this study had normal or below average weight-for-age at baseline, limiting the applicability of these findings to other patient populations.
Cognitive function. It is unclear if oral soy improves cognitive function; research is conflicting. Details: Some research shows that college students who increase consumption of soy foods providing isoflavones 100 mg daily have improved short- and long-term memory (9671). Postmenopausal patients aged 50-65 years who take a soy extract supplement providing isoflavones 60 mg daily also seem to have some improvement in some measures of cognitive function (12048). There is also evidence in postmenopausal patients aged 55-75 years that taking a soy extract supplement providing isoflavones 110 mg daily might improve verbal memory scores (12040). However, another study in this population shows that consuming 25.6 grams daily of soy protein providing 99 mg of isoflavones does not improve cognitive function (12034). Similarly, population research in females aged 42-52 years has found that increasing dietary intake of the isoflavones genistein and daidzein is not associated with improved measures of cognitive function (15042). These differing findings might be explained by variations in study design and soy formulations.
Cognitive impairment. Oral soy has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults 55 years of age and older with mild cognitive impairment shows that taking a specific combination product (DW2009) containing fermented soybean powder and Lactobacillus plantarum daily for 12 weeks modestly improves composite cognitive function when compared with placebo (100319). It is not clear if this effect is due to soy, lactobacillus, or the combination.
Colic. It is unclear if oral soy is beneficial in infants with colic. Details: Preliminary clinical research shows that consuming soy-based formula might reduce the duration of colic symptoms in infants with cows' milk intolerance (75509,75543). However, other clinical research shows that consuming soy-based formula does not improve crying in infants with colic when compared with dicyclomine hydrochloride 3 mg/kg daily (75573). Also, a meta-analysis of only high quality clinical research shows that soy milk formula does not improve the persistence of colic or the duration of crying in infants with colic when compared with control (75611).
Crohn disease. It is unclear if oral soy improves symptoms of Crohn disease. Details: A small observational study in patients with inactive Crohn disease has found that taking oral soy-derived protein in combination with enteral treatment for 4 weeks is associated with increased bowel movements, improved symptoms such as fatigue and mental strain, and increased body weight when compared with standard enteral treatment alone (75175).
Diabetic nephropathy. It is unclear if oral soy improves kidney function in patients with diabetic nephropathy. Details: A meta-analysis of small clinical trials in patients with diabetic nephropathy shows that consuming soy products, such as soy protein and soy milk, modestly reduces proteinuria and blood urea nitrogen (BUN), as well as levels of total and low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose, when compared with animal protein or cow's milk. However, there was no effect on any measures of kidney function (108247). Some individual small clinical trials show that replacing dietary animal protein with soy protein reduces urinary albumin excretion in patients with diabetic nephropathy (7348,12555,12556). However, one small clinical study shows that consuming soy milk 240 mL daily for 4 weeks does not affect urinary creatinine, blood urea nitrogen, proteinuria, or glomerular filtration rate in patients with diabetic nephropathy (90966).
Dyspepsia. Oral soy protein has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with mild or moderate dyspepsia shows that consuming 1 gram of toasted soy flour fermented with Lactobacillus delbrueckii up to three times daily for 3 weeks does not improve heartburn severity or frequency when compared with placebo (105599).
Endometrial cancer. It is unclear if oral soy protein reduces the risk for endometrial cancer. Details: Most epidemiological research has found that increased soy intake is associated with a lower risk of endometrial cancer. Endometrial cancer incidence is lower in Japan, China, and other Asian countries where the typical diet is low in calories and high in soy, whole grain foods, vegetables, and fruits (7338,11036,90954). Also, a large meta-analysis of population research has found that the highest total and fermented soy intake is associated with a 17% to 19% reduced risk of developing endometrial cancer when compared to the lowest intakes in postmenopausal adults (96002). However, one clinical study shows that taking soy protein 25 grams daily providing 91 mg of aglycon equivalents of isoflavones and glycosides for three years does not reduce the risk of endometrial hyperplasia or cancer when compared with placebo in postmenopausal adults. However, this study may not have been adequately powered to detect small differences in the low rates of endometrial hyperplasia (90971).
Fibromyalgia. It is unclear if oral soy reduces fibromyalgia symptoms. Details: Clinical research shows that consuming a shake containing soy protein 20 grams and soy isoflavone 160 mg once daily for 6 weeks does not improve physical functioning or symptoms of depression in patients with fibromyalgia when compared with placebo (75451).
Gastric cancer. It is unclear if oral soy reduces the risk for gastric cancer. Details: Meta-analyses of population research have found that the highest intake of soy-containing foods and nonfermented soy products is associated with a 21% to 37% decreased risk of gastric cancer when compared with the lowest intake (95998,108246). Intake of at least 100 grams daily of nonfermented soy foods was found to be the most protective (95998). However, a high intake of fermented soy products is associated with an increased risk of gastric cancer, and intake of 1-5 cups daily of the fermented soy product miso soup is associated with an increased risk of gastric cancer in males (95998,108246).
Hepatitis C. It is unclear if oral soy is beneficial for hepatitis C. Details: Preliminary clinical research in patients with hepatitis C shows that taking soy protein 32 grams daily for 12 weeks reduces the number of cases of steatosis by 47% and reduces alanine aminotransferase (ALT) levels by 13% when compared to baseline. However, it is no different than taking casein protein (90970).
Irritable bowel syndrome (IBS). A small study suggests that oral soy isoflavones might reduce IBS symptoms. Details: A small clinical study in females with IBS shows that taking soy isoflavones 40 mg daily for 6 weeks improves symptoms of IBS, such as abdominal distention and abdominal pain severity and duration, by approximately 27% when compared with placebo. Quality of life is also improved. Some symptoms are also improved when soy isoflavones are taken in combination with vitamin D; however, the combination of soy isoflavones and vitamin D does not seem to improve symptoms better than soy isoflavones alone (96425).
Lung cancer. It is unclear if dietary soy reduces the risk for lung cancer. Details: A meta-analysis of epidemiological research has found that although increased soy intake is not associated with a reduced risk of lung cancer overall, it is associated with a slightly reduced risk in nonsmoking adults (90985).
Mastalgia. It is unclear if oral soy is beneficial for mastalgia. Details: A small clinical study suggests that soy milk providing 34 grams soy protein daily might reduce cyclical breast pain when compared with no intervention (2428).
Migraine headache. Oral soy has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking a combination of soy isoflavones 60 mg, dong quai 100 mg, and black cohosh 50 mg daily for 24 weeks reduces the frequency of menstrual-associated migraine attacks when compared with placebo (35797). It is not clear if this effect is due to soy, the other ingredients, or the combination.
Neonatal jaundice. It is unclear if oral soy reduces the risk of neonatal jaundice. Details: Clinical research shows that patients with gestational diabetes who consume a diet containing soy protein along with other plant and animal proteins for 6 weeks beginning at 24-28 weeks' gestation have a 73% reduced risk for newborn hyperbilirubinemia when compared with those consuming a control diet containing only non-soy plant and animal proteins (95993).
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral soy is beneficial for the treatment or prevention of NAFLD. Details: Observational research in a Chinese population has found that increased frequency of dietary soy consumption is associated with a lower incidence of NAFLD when compared with lower consumption (105612). A meta-analysis of three small clinical trials in patients living in Iran with NAFLD shows that consuming soy milk, soy foods, or a genistein supplement for 8 weeks might reduce some liver transaminase levels when compared with control (105611). Another meta-analysis of small clinical trials in patients with NAFLD shows that consuming soy milk, soy foods, or a genistein supplement for 8 or 24 weeks modestly improves insulin resistance but does not improve body mass index, cholesterol levels, or liver transaminase levels (108239). These analyses are limited by their generally small population size and the heterogeneity of interventions.
Obesity. It is unclear if consuming oral soy protein as part of a calorie-restricted diet improves weight loss; research is conflicting. Details: Some clinical research shows that consuming soy protein in conjunction with calorie restriction for 2-6 months helps reduce weight in those who are obese and overweight when compared with calorie restriction alone (11085,75397). Other clinical research shows that consuming soy protein for 16 weeks improves weight loss in overweight females when compared with consuming protein from meat (75620). Also, consuming black soy peptide 4.5 grams daily for 12 weeks reduces body weight and body fat mass more than placebo in overweight and obese adults (90961). In addition, some clinical evidence shows that eating biscuits supplemented with soy fiber 100 grams daily for 12 weeks reduces body weight, body mass index (BMI), and low-density lipoprotein (LDL) cholesterol when compared to control in overweight and obese patients (90960). However, contradictory evidence exists. Some clinical research shows that following a calorie-restricted diet and consuming soy-based meal replacements 3-5 times daily for 12-16 weeks, or eating soy protein-rich foods in place of animal protein for 2-12 weeks, does not improve weight loss in overweight or obese individuals when compared to a calorie-restricted diet alone (75277,75372,75376,90968). Also, in overweight and obese females following a free-choice diet, soy protein 56 grams daily for 23 weeks does not appear to improve weight loss when compared to eating an isoenergetic amount of carbohydrates (86077). Finally, a subgroup analysis of six preliminary clinical trials shows that soy products do not improve weight loss in postmenopausal adults (98870). The reason for these disparate findings is unclear but may be due to differences in the soy products used or differences in patient population. For example, a meta-analysis of clinical research shows that phytoestrogen consumption reduces weight in healthy postmenopausal adults but not in those with comorbid conditions (98870). However, the clinical validity of this analysis is limited because it did not evaluate the effect of soy-only phytoestrogens. Soy protein has also been compared with whey protein. One small clinical study in overweight and obese adults shows that patients taking soy protein isolate 52 grams for 23 weeks had similar overall weight and fat loss as those taking whey protein concentrate 52 grams daily (86077). In contrast, another small clinical study in overweight males shows that taking soy isolate 60 grams before lunch daily for 12 weeks is less effective for weight loss when compared with taking whey protein concentrate 65 grams (91801).
Osteoarthritis. It is unclear if oral soy protein reduces osteoarthritis pain. Details: Preliminary clinical research shows that taking soy protein 40 grams daily for three months improves range of motion, pain, and quality of life in osteoarthritis patients, particularly males, when compared to baseline. However, these beneficial effects seem to also be observed following supplementation with milk-based protein, indicating that the benefits may have resulted from a placebo effect (75266).
Overall mortality. It is unclear if dietary soy reduces overall mortality; the available research is conflicting. Details: A meta-analysis of observational studies has found that the highest intake of soy products is not associated with a lower risk of overall mortality, mortality from cardiovascular disease, or mortality from cancer when compared with the lowest intake (96941). However, a more recent population study has found that consuming at least 60 grams of soy daily over a 12-month period is associated with a 17% reduced risk of overall mortality over the next 5 years when compared with consuming less than 15 grams daily (108253). Also, an observational study in Japanese patients followed over 14.8 years has found that although overall soy intake is not associated with any benefit, increased intake of fermented soy products, such as natto and miso, was found to be associated with a slightly reduced risk of mortality (105600).
Polycystic ovary syndrome (PCOS). It is unclear if oral soy reduces PCOS symptoms. Details: Clinical research shows that taking soy isoflavones 50 mg daily for 12 weeks improves insulin levels and insulin resistance by a small amount when compared with placebo in patients with PCOS. Furthermore, taking soy isoflavones improves the free androgen index by approximately 25% and triglyceride levels by 14% when compared to baseline. However, taking soy isoflavones does not improve low- or high-density lipoprotein (LDL or HDL) cholesterol levels or markers of inflammation (95994).
Postmenopausal conditions. It is unclear if oral soy is beneficial for postmenopausal conditions. Details: A meta-analysis of generally small clinical trials in postmenopausal adults shows that taking soy protein with isoflavones or soy isoflavones, usually for 3-24 months, has modest beneficial effects on total cholesterol, and possibly high-density lipoprotein (HDL) cholesterol, when compared with milk protein, soy protein without isoflavones, or placebo. However, there was no effect on low-density lipoprotein (LDL) cholesterol or triglyceride levels. Subgroup analyses show that reductions in LDL cholesterol levels occur when soy is used for less than 6 months, in individuals older than 55 years, and when the soy protein contains isoflavones (108249).
Preterm labor. It is unclear if oral soy reduces the risk for preterm labor. Details: Clinical research in patients with gestational diabetes shows that consuming a diet containing soy protein along with other plant and animal proteins for 6 weeks, beginning at 24-28 weeks' gestation, does not reduce the likelihood for caesarean section, preterm delivery, or maternal hospitalization when compared with a control diet containing only non-soy plant and animal proteins (95993).
Premenstrual syndrome (PMS). It is unclear if oral soy reduces PMS symptoms. Details: Preliminary clinical research in patients with PMS shows that taking isolated soy protein containing soy isoflavones 68 mg daily for two menstrual cycles reduces cramps and swelling when compared with placebo (75279).
Prostate cancer. It is unclear if oral soy is beneficial for the treatment or prevention of prostate cancer; research is conflicting. Details: Observational and clinical research has evaluated the effects of soy intake on prostate cancer risk. Observational research has found that consuming an Asian diet, which contains 10 times more soy than the average American diet, is associated with a lower risk of prostate cancer; however, it is unclear whether it is the soy content of the diet or if genetic differences or environmental factors such as fat ingestion are responsible for this correlation (2298,12884,12886,12887). A meta-analysis of observational trials from North America, Europe, and Asia has found that highest intake of total soy foods, unfermented soy foods, or soy isoflavones is associated with a reduced risk of prostate cancer when compared with the lowest intakes. However, higher intake of fermented soy foods is not associated with a reduced risk (96939). Furthermore, some observational research in Japanese males has found a weak association between increased prostate cancer mortality and a higher dietary intake of soy isoflavones when compared with a lower intake (105607). Research evaluating the use of soy supplements is also conflicting. One clinical study shows that taking soy protein 40 grams daily for 6 months reduces the development of prostate cancer six-fold in those at risk of prostate cancer when compared with milk protein (75432). However, another clinical study in healthy adults aged 50-80 years shows that taking soy protein, providing 83 mg isoflavones, daily for a year does not affect PSA levels when compared with a soy protein drink without isoflavones (12888). Soy products have also been evaluated in patients with prostate cancer. One clinical study shows that consuming a specific bread containing 50 grams of soy, providing 117 mg isoflavones, reduces PSA levels after about 3 weeks of treatment when compared with control (13140). Other preliminary clinical research in patients with rising PSA levels following prior therapy for prostate cancer shows that consuming 8 ounces of soy milk, standardized to contain 47 mg isoflavones, three times daily for 12 months slows the increase in PSA levels from 56% to 20% when compared with baseline (75435). However, one clinical study shows that taking soy protein 40 grams daily for 6 months does not reduce prostate size or improve PSA levels in those diagnosed with prostate cancer when compared with milk protein (75432). Also, in those with early stage prostate cancer, consuming a soy beverage daily providing genistein 60 mg does not seem to affect risk factors for progression of prostate cancer, including testosterone, estradiol, PSA, and sex hormone binding globulin (SHBG) levels (11033). Furthermore, consuming soy protein isolate 20 grams standardized to contain approximately 70 mg isoflavones daily for two years does not prevent prostate cancer recurrence following radical prostatectomy when compared with placebo (90953). Reasons for the discrepancies are not entirely clear, but may include the relatively short trial durations (up to 12 months) and heterogeneity of soy preparations and dosing regimens.
Rheumatoid arthritis (RA). It is unclear if oral soy reduces RA symptoms. Details: Preliminary clinical research in patients with RA shows that consuming a liquid diet containing hydrolyzed soy protein (Top Up) daily for 4 weeks does not improve pain intensity, morning stiffness, or joint swelling and tenderness when compared to consuming a normal daily diet (75619).
Sarcopenia. It is unclear if oral soy reduces age-related muscle loss; evidence is conflicting. Details: Some clinical research in postmenopausal adults shows that consuming soy protein containing isoflavones 99 mg daily for 12 months does not improve hand grip strength or physical performance when compared with a milk protein placebo (75283). However, another small clinical study in older adults with low muscle mass living in China shows that taking soy, or a whey-soy blended protein, 16 grams daily for 6 months, slightly attenuates muscle loss when compared with no intervention (105603).
Stroke. It is unclear if oral soy improves outcomes and overall function in people who have had a stroke. Details: One small clinical study shows that older adults with a history of stroke who consumed soy milk 500 mL daily while participating in a rehabilitation program had greater improvements in hand grip strength, 8-feet walking speed, walking performance, and 6-minute walk test after 8 weeks when compared with placebo. However, consuming soy milk did not lead to greater improvements in lean mass or overall short physical performance battery (SPPB) scores when compared with placebo (100321).
Thyroid cancer. It is unclear if dietary soy reduces the risk for thyroid cancer. Details: Epidemiological research has found that high dietary intake of soy is associated with a reduced risk of thyroid cancer when compared with lower intake (7662,12041).
Vaginal atrophy. It is unclear if topical soy improves vaginal atrophy. Details: A small clinical study in postmenopausal adults with vaginal atrophy shows that applying one gram of soy extract 4% vaginal gel daily for 12 weeks reduces vaginal dryness and pain during sexual intercourse and improves vaginal endometrial thickness when compared with placebo (90964).
Wrinkled skin. Small studies suggest that oral and topical soy might reduce wrinkles. Details: A small clinical study in middle-aged females shows that consuming soy isoflavone 40 mg daily for 12 weeks improves skin elasticity and the appearance of fine wrinkles when compared with placebo (75388). Another small clinical study in females with photodamaged skin shows that applying a soy moisturizer containing soybean trypsin inhibitor and Bowman-Birk protease inhibitor (Aveeno Positively Radiant Daily Moisturizer, Johnson & Johnson CCI) twice daily for 12 weeks improves skin pigmentation, fine lines, texture, tone, and appearance when compared with a placebo moisturizer (75410). More evidence is needed to rate soy for these uses.

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Safety view details

Below is general information about the safety of the known ingredients contained in the product Cappuccino Comfort Fructose. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

COFFEE

LIKELY SAFE ...when used orally and appropriately. Drinking decaffeinated coffee or coffee containing caffeine in low to moderate amounts is safe (15,98806). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, drinking up to 4 cups of coffee daily providing caffeine 400 mg daily is not associated with significant adverse cardiovascular, bone, behavioral, or reproductive effects in healthy adults (11733,98806). The US Dietary Guidelines Advisory Committee states that there is strong and consistent evidence that consumption of beverages such as coffee that contain caffeine 400 mg daily is not associated with increased risk of major chronic diseases, such as cardiovascular disease or cancer, in healthy adults (98806).

POSSIBLY UNSAFE ...when used orally in excessive amounts. Acute use of high doses of caffeine (more than 400 mg per day), which is found in more than 4 cups of caffeinated coffee, has been associated with significant adverse effects such as tachyarrhythmia and sleep disturbances (11832). Drinking caffeinated coffee in amounts greater than 6 cups per day (about 600 mg caffeine) short-term or long-term can also cause caffeinism, with symptoms of anxiety possibly progressing to delirium and agitation. Chronic use of caffeine, especially in large amounts, can sometimes produce tolerance, habituation, and psychological dependence (3719). Abrupt discontinuance of caffeine can cause physical withdrawal symptoms (11733). 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 coffee, 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. ...when used rectally as an enema. Coffee enemas have been linked to cases of severe electrolyte abnormalities and septicemia leading to severe side effects including death (3026,3347,3349,6652).

CHILDREN: POSSIBLY SAFE
when coffee containing caffeine is consumed orally in moderate amounts. Oral intake of caffeine in doses of less than 2.5 mg/kg daily is not associated with significant adverse effects in children and adolescents (11733,98806). However, higher doses should be avoided. The adverse effects typically associated with caffeine-containing coffee are usually more severe in children than adults (11733).

PREGNANCY: POSSIBLY SAFE
when used orally in moderate amounts. Intake of caffeine from coffee and other sources should be monitored during pregnancy. Caffeine crosses the human placenta, but is not considered a teratogen. Fetal blood and tissue levels are similar to maternal concentrations (4260). The use of caffeine during pregnancy is controversial; however, moderate consumption has not been associated with clinically important adverse fetal effects (2708,2709,2710,2711,9606,11733,16014,16015). However, some research has also 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). In some studies, consuming amounts over 200 mg daily has been associated with a significantly increased risk of miscarriage (16014). This increased risk may be most likely to occur in people with genotypes that confer a slow rate of caffeine metabolism (98806). According to a review by Health Canada, and a subsequent large meta-analysis conducted in the US, most healthy pregnant patients can safely consume caffeine in doses up to 300 mg daily without an increased risk of spontaneous abortion, stillbirth, preterm birth, fetal growth retardation, or congenital malformations (11733,98806). Advise patients to keep caffeine consumption below 300 mg daily during pregnancy. This is similar to the amount of caffeine in about 3 cups of coffee. 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 coffee, 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 caffeinated coffee providing more than 300 mg of caffeine daily is consumed orally. Caffeine from coffee 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). Advise patients to keep caffeine consumption from all sources below 300 mg daily during pregnancy. This is similar to the amount of caffeine in about 3 cups of coffee. High doses of caffeine throughout pregnancy have resulted in symptoms of caffeine withdrawal in newborn infants (9891). High doses of caffeine have also been associated with spontaneous abortion, premature delivery, and low birth weight (2709,2711). Drinking more than 6 cups of coffee daily increases the risk of spontaneous abortion (2709). Drinking 8 or more cups of coffee daily doubles the risk of stillbirth when compared with those who do not drink coffee during pregnancy (10621).

LACTATION: POSSIBLY SAFE
when used orally. Drinking one or two caffeine-containing beverages daily during lactation is not associated with unacceptable levels of caffeine in human milk (11734).

LACTATION: POSSIBLY UNSAFE
when used orally in large amounts. Caffeine from coffee can cause wakefulness or irritability in breast-fed infants. Caffeine can also cause feeding intolerance and gastrointestinal irritation in infants (6026).

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SOY (Isoflavone, Soy Protein)

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.

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Interactions with Drugs view details

Below is general information about the interactions of the known ingredients contained in the product Cappuccino Comfort Fructose. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

COFFEE

ADENOSINE (Adenocard)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, coffee might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.

Details

Coffee contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level (38172). However, caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine (11771). It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products, be stopped 24 hours prior to pharmacological stress tests (11770). However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).

ALCOHOL (Ethanol)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, alcohol might increase the levels and adverse effects of caffeine.

Details

Coffee contains caffeine. Concomitant use of alcohol and caffeine can increase caffeine serum concentrations and the risk of caffeine adverse effects. Alcohol reduces caffeine metabolism (6370,24693).

ALENDRONATE (Fosamax)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Coffee reduces alendronate bioavailability.

Details

Separate coffee ingestion and alendronate administration by two hours. Coffee reduces alendronate bioavailability by 60% (11735).

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Unlikely • Level of Evidence = D

Theoretically, coffee may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Details

Coffee contains caffeine. Caffeine is reported to have antiplatelet activity (8028,8029). Theoretically, the caffeine in coffee might increase the risk of bleeding when used concomitantly with these agents. However, this interaction has not been reported in humans. There is some evidence that caffeinated coffee might increase the fibrinolytic activity in blood (8030).

ANTIDIABETES DRUGS

Interaction Rating = Minor Be watchful with this combination.

Severity = Moderate • Occurrence = Unlikely • Level of Evidence = B

Theoretically, concomitant use of coffee and antidiabetes drugs might interfere with blood glucose control.

Details

Coffee contains caffeine. Reports claim that caffeine might increase or decrease blood sugar levels (6024,8646).

BETA-ADRENERGIC AGONISTS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Mild • Occurrence = Probable • Level of Evidence = D

Theoretically, concomitant use of large amounts of coffee might increase cardiac inotropic effects of beta-agonists.

Details

Coffee contains caffeine. Caffeine can increase cardiac inotropic effects of beta-agonists (15).

CIMETIDINE (Tagamet)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Mild • Occurrence = Likely • Level of Evidence = B

Theoretically, cimetidine might increase the effects and adverse effects of caffeine in coffee.

Details

Coffee contains caffeine. Cimetidine can reduce caffeine clearance by 31% to 42% (11736,24700).

CLOZAPINE (Clozaril)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Theoretically, coffee might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.

Details

Coffee contains caffeine. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism (5051). Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients be more sensitive to the interaction between clozapine and caffeine (13741).

CONTRACEPTIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Mild • Occurrence = Probable • Level of Evidence = B

Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in coffee.

Details

Coffee contains caffeine. Oral contraceptive drugs can decrease caffeine clearance by 40% to 65% (2714,11737).

DIPYRIDAMOLE (Persantine)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Theoretically, coffee might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.

Details

Coffee contains caffeine. Caffeine is a methylxyanthine that may inhibit dipyridamole-induced vasodilation (11770,11772,24974,37985,53795). It is recommended that methylxanthines such as caffeine, as well as methylxanthine-containing products such as coffee, be stopped 24 hours prior to pharmacological stress tests (11770). Methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing (11771).

DISULFIRAM (Antabuse)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Mild • Occurrence = Probable • Level of Evidence = B

Theoretically, disulfiram might increase the risk of adverse effects from caffeine.

Details

Coffee contains caffeine. In human research, disulfiram decreases the clearance and increases the half-life of caffeine (11840).

DIURETIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, concomitant use might increase the risk of hypokalemia.

Details

Coffee contains caffeine. Caffeine, especially in excessive amounts, can reduce potassium levels due to stimulation of the sodium-potassium pump (23579,37905,37953,38003,38034). Diuretics can also cause lower potassium levels.

EPHEDRINE

Interaction Rating = Major Do not take this combination.

Severity = High • Occurrence = Probable • Level of Evidence = D

Theoretically, concomitant use might increase the risk of stimulant adverse effects.

Details

Coffee contains caffeine. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death (1275,6486,9740,10307). Tell patients to avoid taking caffeine with ephedrine and other stimulants.

ESTROGENS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Mild • Occurrence = Probable • Level of Evidence = B

Theoretically, estrogens might increase the levels and adverse effects of caffeine.

Details

Coffee contains caffeine. Estrogen inhibits caffeine metabolism (2714).

FLUCONAZOLE (Diflucan)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = B

Theoretically, fluconazole might increase the levels and adverse effects of caffeine.

Details

Coffee contains caffeine. Fluconazole decreases caffeine clearance by approximately 25% (11022,24978).

FLUVOXAMINE (Luvox)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Mild • Occurrence = Probable • Level of Evidence = B

Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.

Details

Coffee contains caffeine. Fluvoxamine reduces caffeine metabolism (6370,38287).

LAMOTRIGINE (Lamictal)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Coffee consumption can decrease the levels and clinical effects of lamotrigine.

Details

A pharmacokinetic study in patients taking lamotrigine shows that consumption of coffee, both caffeinated and decaffeinated, can decrease the area under the concentration-time curve (AUC) and the peak plasma level (Cmax) of lamotrigine. Each additional cup of coffee reduced the AUC and Cmax by 4% and 3%, respectively. It is unclear whether this interaction is due to induction of lamotrigine metabolism or inhibition of lamotrigine absorption (107837).

LEVOTHYROXINE (Synthroid, others)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Coffee can reduce the absorption of levothyroxine.

Details

In some patients, coffee can reduce levothyroxine absorption, possibly through the formation of non-absorbable complexes. A pharmacokinetic study in these patients found that 25-30 mL of espresso coffee consumed with levothyroxine tablets delayed the time to peak plasma levels by 38-43 minutes, reduced the peak plasma level (Cmax) by 19% to 36%, and reduced the area under the curve (AUC) by 27% to 36%. Coffee consumed one hour after levothyroxine did not affect absorption (16401). It is not known whether this interaction occurs with other types of coffee. Tell patients to avoid drinking coffee at the same time that they take their levothyroxine, and for up to an hour afterwards.

LITHIUM

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = D

Theoretically, abrupt coffee withdrawal might increase the levels and adverse effects of lithium.

Details

Coffee contains caffeine. Abrupt caffeine withdrawal can increase serum lithium levels (609). Two cases of lithium tremor that worsened with abrupt coffee withdrawal have been reported (609,610). There is also one case of a 2.8-fold increase in blood lithium levels after a patient taking lithium reduced his coffee consumption from 13-20 cups daily to 10 cups daily (97369).

MEXILETINE (Mexitil)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = B

Theoretically, mexiletine might increase the levels and adverse effects of caffeine.

Details

Coffee contains caffeine. Mexiletine can decrease caffeine elimination by 50% (1260,11741,24981).

MONOAMINE OXIDASE INHIBITORS (MAOIs)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, concomitant use might increase the risk of a hypertensive crisis.

Details

Coffee contains caffeine. Caffeine has been shown to inhibit monoamine oxidase (MAO) A and B in laboratory studies (37724,37877,37912,38108). Concomitant intake of large amounts of caffeine with MAOIs might precipitate a hypertensive crisis (15). In a case report, a patient that consumed 10-12 cups of caffeinated coffee and took the MAOI tranylcypromine presented with severe hypertension (91086). Hypertension was resolved after the patient switched to drinking decaffeinated coffee.

NICOTINE

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Theoretically, concomitant use might increase the risk of hypertension.

Details

Coffee 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).

PENTOBARBITAL (Nembutal)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, coffee might reduce the effects of pentobarbital.

Details

Coffee contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital (13742).

PHENOTHIAZINES

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, phenothiazines might increase the levels and adverse effects of caffeine. Also, coffee may bind to phenothiazines and reduce their absorption.

Details

Coffee contains caffeine. Phenothiazines can reduce the metabolism of caffeine by inhibiting cytochrome P450 1A2 (CYP1A2) (23573,23574). Additionally, the tannins in coffee may bind to phenothiazines in the gastrointestinal tract and reduce their absorption (626,627).

PHENYLPROPANOLAMINE

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.

Details

Coffee contains caffeine. Concomitant use of phenylpropanolamine and caffeine might cause an additive increase in blood pressure (11738). Phenylpropanolamine also seems to increase caffeine serum levels (13743).

PIOGLITAZONE (Actos)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, coffee might increase the levels and clinical effects of pioglitazone.

Details

Coffee contains caffeine. Animal research suggests that caffeine can modestly increase the maximum concentration, area under the curve, and half-life of pioglitazone, and also reduce its clearance. This increased the antidiabetic effects of pioglitazone (108812). However, the exact mechanism of this interaction is unclear.

QUINOLONE ANTIBIOTICS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Mild • Occurrence = Probable • Level of Evidence = B

Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.

Details

Coffee contains caffeine. Concomitant use of caffeine and quinolones can decrease caffeine clearance and increase effects and risk of adverse effects (606,607,608,23555,24695,24696,24697).

RILUZOLE (Rilutek)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.

Details

Coffee contains caffeine. Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), and concomitant use might reduce metabolism of one or both agents (11739).

STIMULANT DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = C

Theoretically, concomitant use might increase stimulant adverse effects.

Details

Coffee contains caffeine. Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects (11832).

TERBINAFINE (Lamisil)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = B

Theoretically, terbinafine might increase the levels and adverse effects of caffeine.

Details

Coffee contains caffeine. Terbinafine decreases the clearance of intravenous caffeine by 19% (11740).

THEOPHYLLINE

Interaction Rating = Moderate Be cautious with this combination.

Severity = Mild • Occurrence = Probable • Level of Evidence = B

Theoretically, coffee might increase the levels and adverse effects of theophylline.

Details

Coffee contains caffeine, which can increase theophylline levels (11741,11862,24984).

TRICYCLIC ANTIDEPRESSANTS (TCAs)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, TCAs might bind with coffee constituents when taken at the same time.

Details

In vitro research suggests that the tannins in coffee might cause precipitation of TCAs (626,627). However, this effect has not been reported in humans.

VERAPAMIL (Calan, others)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, concomitant use might increase the levels and adverse effects of caffeine.

Details

Coffee contains caffeine. Verapamil increases plasma caffeine concentrations by 25% (11741).

(Read more about COFFEE)

SOY (Isoflavone, Soy Protein)

ANTIBIOTIC DRUGS

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, antibiotics may decrease the activity of soy isoflavones.

Details

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).

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = A

Soy can lower blood glucose and have additive effects with antidiabetes drugs.

Details

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).

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = A

Theoretically soy protein may have additive effects with antihypertensive drugs and increase the risk of hypotension.

Details

Although some contradictory research exists (14254), most clinical evidence suggests that consuming soy protein modestly reduces systolic and diastolic blood pressure in individuals with prehypertension or hypertension (13139,75482).

CAFFEINE

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, soy might reduce the clearance of caffeine.

Details

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.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Moderate • Occurrence = Unlikely • Level of Evidence = D

Soy might modestly induce CYP2C9 enzymes. However, this effect does not seem to be clinically significant.

Details

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).

DIURETIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, soy might have additive effects when used with diuretic drugs.

Details

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.

ESTROGENS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, soy might competitively inhibit the effects of estrogen replacement therapy.

Details

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.

LEVOTHYROXINE (Synthroid, others)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Soy products might reduce the absorption of levothyroxine in some patients.

Details

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).

MONOAMINE OXIDASE INHIBITORS (MAOIs)

Interaction Rating = Major Do not take this combination.

Severity = High • Occurrence = Likely • Level of Evidence = C

Taking soy products containing high amounts of tyramine along with MAOIs can increase the risk of hypertensive crisis.

Details

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.

PROGESTERONE

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = A

Theoretically, combining soy isoflavones with transdermal progesterone may worsen bone density.

Details

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).

TAMOXIFEN (Nolvadex)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Theoretically, estrogenic soy isoflavones might alter the effects of tamoxifen.

Details

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.

WARFARIN (Coumadin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, soy might interfere with the effects of warfarin.

Details

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.

(Read more about SOY)

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Adverse Effects view details

Report an Adverse Reaction to Cappuccino Comfort Fructose

Below is general information about the adverse effects of the known ingredients contained in the product Cappuccino Comfort Fructose. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

COFFEE

General ...Orally, caffeinated or decaffeinated coffee is well tolerated in moderate amounts.
Most Common Adverse Effects:
Orally: Drinking coffee containing caffeine can cause agitation, anxiety, chest pain, diuresis, gastric distress, headache, insomnia, nervousness, premature heart rate, ringing in the ears, and vomiting. These effects are more likely with increasing intake of caffeine and in certain populations (e.g., children, elderly). With chronic caffeine use, especially in large amounts, habituation, tolerance, and psychological dependence can occur.
Abrupt discontinuation of caffeine may result in physical withdrawal symptoms, including anxiety, decreased physical energy, depressed mood, difficulty concentrating, drowsiness, fatigue, headache, irritability, reduced alertness, and rhinorrhea.
Rectally: Coffee enemas have been linked to proctocolitis, severe electrolyte abnormalities, and septicemia leading to death.

Cardiovascular ...Orally, coffee containing caffeine can cause chest pain and premature heartbeat (8042,111045). These effects are more likely with increasing intake of caffeine and in certain populations (e.g., children, elderly) (8042). Excessive doses of caffeine can cause massive catecholamine release and subsequent sinus tachycardia (11832,11838,13734,13735).
Although acute administration of caffeine can cause increased blood pressure, regular consumption does not seem to increase either blood pressure or pulse, even in hypertensive patients (1451,1452,2722,13739,105312). Drinking one or more cups of caffeinated coffee daily also doesn't seem to increase the risk of developing hypertension in habitual coffee drinkers (8033,13739,111037).
Epidemiological research has found that regular caffeine intake of up to 400 mg daily, or approximately 4 cups of caffeinated coffee, is not associated with an increased incidence of atrial fibrillation (38018,38076,91028,91034,97451,97453,105310), atherosclerosis (38033), cardiac ectopy (91127), stroke (37804), ventricular arrhythmia (95948,97453,105310), or cardiovascular disease (CVD) in general (37805,98806,104882). However, some observational research suggests that drinking at least 1 cup of coffee per week is associated with a 40% increased risk of atrial fibrillation, with the highest incidence of atrial fibrillation occurring in adults consuming at least 6 cups daily (111042). Also, one large, observational study found a J-shaped association between regular coffee consumption and the risk of developing acute coronary syndromes. Moderate consumption of less than 300 mL daily (about 1.3 cups) was associated with a lower risk of developing acute coronary syndromes, whereas regular consumption of 300 mL daily or more was associated with an increased risk (11318). In contrast, other observational research in people without a history of CVD has found that drinking more than 6 cups of coffee daily does not appear to be associated with an increased risk of developing coronary heart disease (14343). Also, in people with a history of CVD, population research has found that coffee consumption is associated with a reduction in CVD-related mortality (97373,97374,103997,103998,104594,104595,104882,105308,105311,105313,105314). However, in current smokers with a history of acute coronary syndrome, consuming more than 3 cups of coffee daily is associated with more than a two-fold increased risk of overall mortality (105313). Also, population research in patients with severe hypertension, but not mild hypertension, suggests that drinking at least two cups of coffee daily is associated with a 2-fold increase in CVD mortality compared with non-coffee drinkers (111027).
Caffeine intake may pose a greater cardiovascular risk to subjects who are not regular caffeine users. Population research suggests that drinking caffeinated coffee might trigger a myocardial infarction (MI) in some people. People who drink one or fewer cups of coffee daily and are sedentary and have multiple risk factors for heart disease have a significantly increased risk of MI within an hour after drinking coffee. However, this risk appears diminished in people who routinely consume greater amounts of coffee on a daily basis (14497). In another population study, caffeinated coffee consumption was associated with an increased risk of ischemic stroke in subjects who didn't regularly drink coffee (38102).
Boiled coffee that is prepared without a filter appears to increase serum cholesterol and triglyceride levels (1353,4200,8036,8539). Drinking one liter of strong, unfiltered coffee daily for two weeks can raise serum cholesterol by 10% and serum triglycerides by 36% (1353). Tell patients to use coffee filters since these effects do not seem to occur with filtered coffee (4200,8036,8539).
Coffee can adversely affect homocysteine levels. Higher homocysteine levels have been associated with CVD. One liter of unfiltered strong coffee daily for two weeks can increase plasma homocysteine levels by 10% (1353). The same amount of filtered strong coffee appears to raise plasma homocysteine levels by 20%, although there have been no head-to-head comparisons of filtered versus unfiltered coffee (3344).

Dermatologic ...Some researchers suggest symptoms such as flushed face occur during caffeine withdrawal. However, withdrawal symptoms may be due to nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).

Endocrine ...Orally, excessive doses of caffeine can cause massive catecholamine release and subsequent metabolic acidosis, hyperglycemia, and ketosis (13734). Other symptoms include hypokalemia and respiratory alkalosis (11832,11838,13735).
Some evidence shows that caffeine, a constituent of coffee, is associated with fibrocystic breast disease, breast cancer, and endometriosis in females; however, this is controversial since findings are conflicting (8043). Restricting caffeine intake in patients with fibrocystic breast conditions doesn't seem to affect breast nodularity, swelling, or pain (8996). Population research suggests that exposure to caffeine is not associated with an increased risk of endometriosis (91035).
A population analysis of the Women's Health Initiative observational study has found no association between consumption of caffeine-containing beverages, such as coffee, and the incidence of invasive breast cancer in models adjusted for demographic, lifestyle, and reproductive factors (108806). Also, a dose-response analysis of 2 low-quality observational studies has found that high consumption of caffeine is not associated with an increased risk of breast cancer (108807).

Gastrointestinal ...Orally, coffee containing caffeine can cause gastric distress and vomiting. These effects are more likely with increasing intake of caffeine and in certain populations (e.g., children, elderly) (8042,13734). There is also some evidence that consumption of three or more cups of caffeinated coffee might increase the risk of Helicobacter pylori infection (8034).
Caffeine withdrawal symptoms such as nausea and vomiting have been described. However, these symptoms may be due to nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).
Rectally, at least 5 cases of proctocolitis related to the use of coffee enemas have been reported (96868,103273).

Genitourinary ...The caffeine found in coffee is a known diuretic and may increase voiding, give a sense of urgency, and irritate the bladder (37874,37961,104580). In males with lower urinary tract symptoms, caffeine intake increased the risk of interstitial cystitis/painful bladder syndrome (38115). Excessive caffeine consumption may worsen premenstrual syndrome. Consumption of up to 10 cups of caffeinated drinks daily has been associated with increased severity of premenstrual syndrome (38177).

Hematologic ...There is evidence that coffee containing caffeine shortens whole blood fibrinolysis time (8030).
Rectally, coffee enemas have been linked to severe electrolyte abnormalities leading to death (3026,3347,3349,6652)

Hepatic ...Boiled coffee that is prepared without a filter appears to increase liver aminotransferase enzymes. Tell patients to use coffee filters since these effects do not seem to occur with filtered coffee (8539).

Immunologic ...Caffeine can cause anaphylaxis in sensitive individuals, although true IgE-mediated caffeine allergy seems to be relatively rare (11315).
Rectally, coffee enemas have been linked to septicemia leading to death (3026,3347,3349,6652).

Musculoskeletal ...Orally, there is preliminary evidence that use of greater than four cups of coffee daily can increase the risk of rheumatoid factor positive rheumatoid arthritis, but this association has not been confirmed (6482).
Epidemiological evidence regarding the relationship between caffeine use and the risk for osteoporosis is contradictory. Caffeine can increase urinary excretion of calcium (2669,10202,11317). Females identified with a genetic variant of the vitamin D receptor appear to be at an increased risk for the detrimental effect of caffeine on bone mass (2669). However, moderate caffeine intake of less than 400 mg daily does not seem to significantly increase osteoporosis risk in most postmenopausal adults with normal calcium intake (2669,6025,10202,11317,98806).
Caffeine withdrawal symptoms, such as muscle tension and muscle pains, have been described. However, these symptoms may be due to nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).

Neurologic/CNS ...Orally, coffee containing caffeine can cause agitation, headache, insomnia, and nervousness, . These effects are more likely with increasing intake of caffeine and in certain populations (e.g., children, elderly) (8042,11832,11838,13734,13735).
Combining ephedra with coffee can increase the risk of adverse effects, due to the caffeine contained in coffee. Jitteriness, seizures, and temporary loss of consciousness have been associated with the combined use of ephedra and caffeine (2729).
Some researchers suggest that symptoms such as headache; tiredness and fatigue; decreased energy, alertness, and attentiveness; drowsiness; decreased contentedness; difficulty concentrating; irritability; and lack of clear-headedness are typical of caffeine withdrawal (13738). Withdrawal symptoms such as delirium, nervousness, and restlessness have also been described. However, these symptoms may be due to nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).

Ocular/Otic ...Orally, coffee containing caffeine can cause ringing in the ears. This is more likely with increasing intake of caffeine and in certain populations (e.g., children, elderly) (8042,13734). Coffee containing caffeine also increases intraocular pressure, starting about 30 minutes after consumption and persisting for at least 90 minutes. Decaffeinated coffee does not appear to affect intraocular pressure (8540).

Oncologic ...The association between consumption of coffee and pancreatic cancer is controversial. Coffee may increase the incidence of some types of pancreatic cancers, but it may decrease other types (8535,8536,8537). Some studies do not support this association, especially in patients that have never smoked (8038,8040,93878,103999). Patients who are at risk of pancreatic cancer (pancreatitis) should limit their consumption of coffee.
People who consume 2-4 or more cups of caffeinated coffee dail might have a significantly increased risk of developing lung cancer (13191,90177). But drinking decaffeinated coffee seems to be associated with a decreased risk of lung cancer (13191).
Coffee consumption has also been associated at various times with an increased risk of breast cancer, bladder cancer, colon cancer, and other types of cancers, but there's no good evidence that coffee consumption increases cancer risk (8039,8040,8041). Most human studies that have examined caffeine or coffee intake have found that they do not play a role in the development of various cancers, including breast or most gastric cancers (91054,91076,98806). However, drinking caffeinated coffee might increase the risk of gastric cardia cancer (91076).

Psychiatric ...Orally, coffee containing caffeine can cause anxiety. This is more likely with increasing intake of caffeine and in certain populations (e.g., children, elderly) (8042,13734). With chronic use, especially in large amounts, habituation, tolerance, and psychological dependence can occur (3719). Other researchers suggest symptoms such as depressed mood are typical of caffeine withdrawal (13738). However, withdrawal symptoms may be due to nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).

Pulmonary/Respiratory ...Caffeine withdrawal symptoms such as rhinorrhea have been described. However, these symptoms may be due to nonpharmacological factors related to knowledge and expectation of effects. Clinically significant symptoms caused by caffeine withdrawal may be uncommon (2723,11839).

Renal ...Orally, coffee containing caffeine can cause diuresis. This is more likely with increasing intake of caffeine and in certain populations (e.g., children, elderly) (8042,13734).

(Read more about COFFEE)

SOY (Isoflavone, Soy Protein)

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).

(Read more about SOY)

Report an Adverse Reaction to Cappuccino Comfort Fructose

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