Colostrum with Beta Glucan by DC

LIKELY EFFECTIVE

• Coronary heart disease (CHD). Consuming products containing at least 3.6 grams of soluble fiber, including beta-glucans, per day may reduce the risk of CHD when consumed as part of a diet low in saturated fat and cholesterol. Details: Clinical research shows that a diet containing foods high in beta-glucans, such as oats and barley, reduces the risk of heart disease (2737,4960,4962,4963,4964,4965,4966,4967,4968). In 1993, the FDA approved a health claim stating that consuming products containing at least 3 grams of beta-glucans per day, as part of a diet low in saturated fat and cholesterol, may reduce the risk of CHD (102336). However, clinical studies show that at least 3.6 grams of soluble fiber daily is needed to reduce the risk of CHD (5786,5787,5788,5794,5795,5796).
• Dyslipidemia. Oral beta-glucans modestly reduces low-density lipoprotein (LDL) cholesterol levels. Details: Although some research disagrees, most clinical research shows that taking barley- or oat-derived beta-glucans 3-10 grams daily for up to 12 weeks or yeast-derived beta-glucans 7.5 grams twice daily for 7-8 weeks can reduce LDL and total cholesterol levels when used for up to 12 weeks (5790,5796,7272,17129,34700,34727,34729,34765,34766,34811)(34812,34876). Meta-analyses of available clinical research on oat-derived beta-glucans show that taking at least 3 grams daily reduces LDL cholesterol by around 4-10 mg/dL and total cholesterol by 4-12 mg/dL but does not affect high-density lipoprotein (HDL) cholesterol or triglyceride levels when compared with control diets (92660,97987,112225). Consuming oat-derived beta-glucans also reduces apolipoprotein B (apoB) levels by 0.54 mg/dL when compared with control diets (97987). The effects of oat-derived beta-glucans on cholesterol levels appear to be greater in patients with diabetes and those with higher LDL cholesterol levels (92660,97987). A meta-analysis of available clinical research on barley-derived beta-glucans shows that consuming an average of 6.5-7 grams of beta-glucans daily as part of the diet reduces LDL cholesterol levels by 4.5 mg/dL, total cholesterol levels by 5.6 mg/dL, and apoB levels by 0.54 mg/dL when compared with control diets (98204). The form of beta-glucans used may alter the effect of beta-glucans on cholesterol levels. Some research shows that barley that is highly enriched (75% by weight) with beta-glucans does not significantly affect cholesterol levels. This lack of effect seems to be the result of processing the barley into a highly enriched beta-glucans product (10166). Other clinical research also shows that the processing of beta-glucans products or the food matrix used to make these products might reduce beta-glucans molecular weight and/or solubility and therefore decrease its ability to lower cholesterol levels (10145,34800,34819).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there is interest in using oral or topical beta-glucans for aging, there is insufficient reliable information about the clinical effects of beta-glucans for this purpose.
• Allergic rhinitis (hay fever). It is unclear if oral beta-glucans are beneficial for reducing symptoms of allergic rhinitis. Details: A small clinical trial in patients allergic to ragweed shows that taking specific yeast-derived beta-glucans (Wellmune WGP) 250 mg daily for 4 weeks decreases the number of allergy symptoms by 28% and the severity of allergy symptoms by 52% when compared with placebo (34859).
• Atopic dermatitis (eczema). It is unclear if topical beta-glucans are beneficial for atopic dermatitis. Details: Preliminary clinical research in children and adults with atopic dermatitis shows that applying a specific cream (Imunoglukan P4H, PLEURAN s.r.o.) containing beta-glucans 0.25% 2-3 times daily for 6 months modestly reduces pruritus, intensity of flares, and overall disease severity when compared with the application of a standard emollient (98201).
• Benign prostatic hyperplasia (BPH). Although there is interest in using oral beta-glucans for BPH, there is insufficient reliable information about the clinical effects of beta-glucans for this purpose.
• Cancer. Although there is interest in using oral beta-glucans for cancer, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Canker sores. It is unclear if oral beta-glucans are beneficial for canker sores. Details: Preliminary clinical research shows that taking beta-glucans 10 mg twice daily for 20 days reduces ulcer severity in patients with recurrent aphthous stomatitis when compared with placebo (34763).
• Chronic fatigue syndrome (CFS). Although there is interest in using oral beta-glucans for CFS, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Critical illness (trauma). It is unclear if oral beta-glucans are beneficial for patients with critical illness. Details: Preliminary clinical research shows that taking oat-derived beta-glucans 3 grams daily as part of enteral feeds does not reduce the length of hospital stay, mortality rate, or infection rate when compared with placebo in patients with trauma. However, the length of time on mechanical ventilation was approximately 47% shorter when compared with placebo (100186).
• Diabetes. Small clinical studies in children and adults with type 1 diabetes suggest that beta-glucans do not improve blood glucose levels. It is unclear if oral beta-glucans are beneficial for patients with type 2 diabetes. Details: Some preliminary clinical research in adults with type 2 diabetes shows that consuming oat-derived beta-glucans 3 grams daily in bread for 3 weeks improves insulin resistance and cholesterol levels when compared with control bread (34765). Other preliminary clinical research in patients with type 2 diabetes shows that consuming bread containing oat-derived beta-glucans in a ratio of 7.6 grams per 100 grams of starch daily for 6 months reduces postprandial glucose levels and glycated hemoglobin (HbA1c) when compared with control bread (97986). Additionally, some clinical research shows that replacing a half serving of white rice with beta-glucans-containing barley attenuates increases in postprandial glucose and insulin levels when compared with a full serving of white rice in patients with type 2 diabetes (103887). However, oat-derived beta-glucans 3-3.5 grams daily in bread or soup for 3-8 weeks does not seem to significantly affect fasting plasma glucose levels or HbA1c when compared with control bread or soup (34765,34788). Also, some evidence shows that consuming soup enriched with beta-glucans does not improve cholesterol levels in patients with type 2 diabetes when compared with control soup (34788). The inconsistency in clinical outcomes may be due to differences in the length of treatment, quantity or ratio of beta-glucans consumed, and/or the preparation of the beta-glucans product. In children with type 1 diabetes, consuming a bedtime snack enriched in beta-glucans appears to prevent hypoglycemia prior to midnight, but does not prevent hypoglycemia at later time points when compared with a control snack (34685). In adolescents with type 1 diabetes, a very small clinical study shows that taking a specific oat product (Betaglucare), providing 6 grams beta-glucans, in three divided doses daily for one week is beneficial for glycemic control and variability when compared with a standard diet without beta-glucans or with 3 grams beta-glucans daily. Maximal, mean, and pre- and post-meal blood glucose levels were modestly lower, and minimal blood glucose levels were modestly higher. Most measures of glycemic variability were statistically different, although there were no differences in the durations of hypoglycemia or hyperglycemia between groups (105261). However, a small crossover study in adults with type 1 diabetes shows that taking a specific product (Stomacol, Brainbridge Commerce AB) containing beta-glucans 1.53 grams 3 times daily prior to meals for 2 weeks does not alter blood glucose levels when compared with placebo (97983).
• Exercise-induced respiratory infections. There is conflicting evidence about the effects of beta-glucans on respiratory infections in athletes following competitive events. Details: Taking a specific product containing oat beta-glucans (OatVantage) 5.6 grams daily for 14 days does not reduce the number of sick days or the number of upper respiratory tract infections in trained male cyclists when compared with placebo (34746). However, other clinical research shows that taking yeast-derived beta-glucans 250-500 mg daily for 4 weeks beginning on the day after a marathon reduces the occurrence of symptomatic upper respiratory infections by 33% to 50% within 2-4 weeks of treatment when compared with placebo. Health scores, fatigue, and mood also improved (34860,92659). Additional clinical research in marathon runners shows that drinking a beverage containing yeast-derived beta-glucans 250 mg daily for 45 days prior to, the day of, and 45 days after a marathon does not reduce the duration or number of upper respiratory infections, but does seem to reduce the number of symptomatic days and overall severity of upper respiratory symptoms, when compared with placebo (103886). Finally, clinical research in top athletes also shows that taking a specific product containing mushroom-derived beta-glucans (Imunoglukan P4H, PLEURAN s.r.o.) 200 mg with vitamin C 200 mg daily for 3 months reduces the number of subjects with at least four symptoms of upper respiratory tract infection by approximately 85% when compared with vitamin C alone (34809).
• Fibromyalgia. Although there is interest in using oral beta-glucans for fibromyalgia, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Hepatitis. Although there is interest in using oral beta-glucans for hepatitis, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Hypertension. It is unclear if oral beta-glucans are beneficial for hypertension; the available evidence is conflicting. Details: Preliminary clinical research shows that consuming an oat cereal containing beta-glucans 5.52 grams daily for 6 weeks reduces diastolic and systolic blood pressure when compared with a low-fiber cereal in hypertensive adults (34691). However, other clinical research shows that consuming oat-based cereals enriched in beta-glucans for 12 weeks does not reduce blood pressure in individuals with hypertension. A reduction in blood pressure occurred in a sub-group of these individuals with a body mass index greater than 31.5 kg/m2 (34684,34722).
• Inflammatory bowel disease (IBD). Oral beta-glucans have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research in adults with IBD and symptoms of irritable bowel syndrome shows that taking a combination of beta-glucans, inositol, and digestive enzymes daily for 4 weeks, in conjunction with mesalamine, reduces evacuative urgency when compared with mesalamine alone. Taking this combination product also reduces abdominal pain, bloating, and gas when compared with baseline, but not when compared with taking mesalamine alone (97984).
• Irritable bowel syndrome (IBS). Oral beta-glucans have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research shows that taking one pill twice daily of a specific combination product (Biointol, BioActivaL) containing beta-glucans, inositol, and digestive enzymes for 4 weeks reduces pain, bloating, and gas, but not other symptoms of IBS, when compared with no treatment (34818). It is not clear if these effects are due to beta-glucans, the other ingredients, or the combination.
• Laser skin resurfacing. It is unclear if topical beta-glucans are beneficial for improving recovery from laser skin resurfacing. Details: In patients that had received fractional laser therapy for atrophic acne scars, preliminary clinical research shows that topical application of skin care products containing beta-glucans, including dressings, solutions, and creams, (Dermdoc, Songyang Biotechnology Co. Ltd) once daily to one side of the face for 14 days modestly increases hydration and reduces redness when compared with the other side of the face treated with the vehicle alone (105263).
• Lower respiratory tract infections. Oral beta-glucans have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research in children aged 2-6 years with recurrent respiratory tract infections shows that taking a specific combination product (Stimunex gocce) containing beta-glucans, elderberry extract, zinc, and vitamin D3 does not reduce the number or duration of lower respiratory tract infections when compared with no treatment. In the four months after treatment completion, the number of infections was reduced by about 50%; however, the total number of infections in each group was small. The dose was 1 drop/kg daily for one month, followed by 1 drop/kg daily for 15 consecutive days each month for the next three months (109212).
• Lyme disease. Although there is interest in using oral beta-glucans for Lyme disease, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Metabolic syndrome. It is unclear if oral beta-glucans are beneficial for metabolic syndrome. Details: Preliminary clinical research in adults with metabolic syndrome or at high risk for metabolic syndrome shows that eating 200 grams of bread enriched with 6% barley-derived beta-glucans daily for 4 weeks as part of the diet does not alter most metabolic parameters when compared with baseline. However, there was a small reduction in total cholesterol (100185). The validity of this finding is limited by the lack of a comparator group.
• Multiple sclerosis (MS). Although there is interest in using oral beta-glucans for MS, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Neuroblastoma. It is unclear if oral beta-glucans is beneficial in children or young adults with neuroblastoma. Details: Clinical research in children and young adults with relapsed or refractory high-risk neuroblastoma shows that taking yeast-derived beta-glucans for 17 days, starting four days before treatment with intravenous anti-GD2 murine monoclonal antibody for a total of 10 days, results in progression-free and overall survival rates of 28% and 61%, respectively, after 2 years, and 19% and 36%, respectively, after 5 years. Doses of beta-glucans ranged from 10-200 mg/kg daily and each patient completed 1-4 treatment cycles (109203). The validity of these findings is limited by the lack of statistical comparison to a control group. A large clinical study in children and young adults with high-risk neuroblastoma receiving subcutaneous GD2/GD3 vaccine shows that taking beta-glucans 40 mg/kg/day for 14 days as a primer to the vaccine improves the IgG antibody response at 32 weeks when compared with controls who started taking beta-glucans 6 weeks after vaccination. However, taking beta-glucans prior to vaccination does not improve overall or progression-free survival at approximately 20 months (112227). This study may have been inadequately powered to detect a difference in survival between groups.
• Obesity. It is unclear if oral beta-glucans are beneficial for obesity. Details: A meta-analysis of 20 randomized controlled trials shows that taking beta-glucans reduces body weight by about 0.8 kg and body mass index (BMI) by about 0.6 kg/m2 when compared with not taking beta-glucans. However, there was no effect on waist circumference. Also, populations included in this meta-analysis included those with obesity, as well as healthy individuals and patients with diabetes or hypercholesterolemia (100183). Results from individual clinical trials are mixed, with some showing modest reductions in body weight, BMI, and/or waist circumference, and others showing no effect (34790,98202,98203,100183,109208). This research has evaluated barley-, oat-, or yeast-derived beta-glucans at doses between 0.88-9 grams daily for 0.4-12 weeks (34790,98202,98203,100183,109208). Also, a capsule containing yeast-derived beta-glucans 477 mg has been taken daily for 2 weeks, then twice daily for 4 weeks (98203). Beta-glucans have also been taken in combination with other ingredients. For example, barley-derived beta-glucans 2.2 grams has been mixed with rice and consumed twice daily with meals for 12 weeks (98202) and oat-derived beta-glucans (B-Can, Garuda International, Inc.) 2.5 grams has been taken with green coffee polyphenols 300 mg twice daily for 8 weeks (109208). The inconsistency in clinical outcomes may be due to the heterogenous patient populations, as well as the differing sources, doses, and dosage forms of beta-glucans used.
• Otitis media. Although there is interest in using oral beta-glucans for otitis media, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Postoperative pain. It is unclear if oral beta-glucans are beneficial for reducing abdominal pain after surgery for intestinal polyps. Details: Preliminary clinical research in patients who underwent surgical removal of intestinal polyps shows that eating bread containing barley beta-glucans 3 grams daily for 3 months reduces bloating and abdominal pain when compared with eating bread that does not contain beta-glucans (34813).
• Respiratory tract infections. Oral beta-glucans have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research in children aged 2-6 years with recurrent respiratory tract infections shows that taking a specific combination product (Stimunex gocce) containing beta-glucans, elderberry extract, zinc, and vitamin D3 reduces the duration of respiratory tract infections by about 1.7 days and modestly improves parent-perceived symptom severity and effectiveness when compared with no treatment. However, there was no effect on the number of total, upper, or lower respiratory tract infections, the use of antibiotics or antipyretics, or the number of days missed from school. The product was dosed as 1 drop/kg daily for one month, followed by 1 drop/kg daily for 15 consecutive days each month for the next three months (109212).
• Rheumatoid arthritis (RA). Although there is interest in using oral beta-glucans for RA, there is insufficient reliable information about the clinical effects of beta-glucans for this condition.
• Stretch marks (striae gravidarum). It is unclear if topical beta-glucans are beneficial for stretch marks. Details: Preliminary clinical research shows that a specific topical serum and emulsion (Awake; Hangzhou Songyang Biotechnical) containing beta-glucans, applied twice daily for 12 weeks, modestly improves patient-scored, but not physician-scored, stretch mark appearance when compared with a vehicle control. When beta-glucans are used in combination with 1565-nm non-ablative fractional laser once every 4 weeks for 12 weeks, scar atrophy is modestly improved when compared with either treatment alone (109210). However, it is unclear if any changes would be considered clinically significant.
• Upper respiratory tract infection (URTI). It is unclear if oral beta-glucans are beneficial for the prevention of URTIs in adults or children. Details: A meta-analysis of clinical research shows that taking yeast-derived beta-glucans reduces the odds of developing a URTI in generally healthy individuals by approximately 65% when compared with placebo. There was also a small to medium effect on the overall incidence and duration of URTIs. Doses ranged from 35-900 mg daily for 4-26 weeks (105264). However, the results from this analysis were heterogeneous and the number of studies included was small. One study included in the analysis used a specific product containing yeast-derived beta-glucans (Wellmune WGP) 500 mg daily for 12 weeks and found no effect on the number or duration of overall symptomatic infections or the number or duration of specific types of respiratory infections when compared with placebo. However, there was an improvement in quality of life and a reduction in the number of missed work days (34879). Beta-glucans have also been evaluated for the prevention of URTI in children. A small clinical study in children aged 2-6 years with recurrent respiratory tract infections shows that taking a specific combination product (Stimunex gocce) containing beta-glucans, elderberry extract, zinc, and vitamin D3 does not reduce the number or duration of upper respiratory tract infections when compared with no treatment. At four months after treatment completion, the number of infections was reduced by about 44%; however, the total number of infections in both groups was small. The product was dosed as 1 drop/kg daily for one month, followed by 1 drop/kg daily for 15 consecutive days each month for the next three months (109212).
• Wound healing. Although there is interest in using topical beta-glucans for healing of wounds, burns, skin ulcers, and dermatitis, there is insufficient reliable information about the clinical effects of beta-glucans for these purposes. More evidence is needed to rate beta-glucans for these uses.

(Read more about BETA-GLUCANS)

POSSIBLY EFFECTIVE

• Pregnancy-related iron deficiency. Oral lactoferrin seems to improve hemoglobin levels similarly to oral or parenteral iron therapy in patients with pregnancy-related iron deficiency. Details: A meta-analysis of 4 clinical studies in patients with pregnancy-related iron deficiency anemia shows that taking bovine lactoferrin 200-250 mg daily for 4-8 weeks during the second or third trimester is equally effective to ferrous sulfate 150-520 mg for improving hemoglobin levels (97788). Another meta-analysis of 6 mostly small, low-quality clinical studies in pregnant patients with iron deficiency anemia, iron deficiency, or hereditary thrombophilia shows that taking lactoferrin improves hemoglobin and serum iron, but not serum ferritin, when compared with ferrous sulfate (110773). However, the validity of these findings is limited by the heterogeneity of the included studies and lack of information about lactoferrin and iron doses.
• Sepsis. Oral lactoferrin seems to reduce the risk of late-onset sepsis in some premature infants. However, the optimal dosing regimen and patient population is unclear. Details: A meta-analysis of 12 clinical studies in premature infants shows that lactoferrin 150-200 mg/kg daily reduces the risk of late-onset sepsis by 20%, largely due to reductions in fungal infections specifically (104868). In contrast, other meta-analyses have reported conflicting findings (97783,104856) and some suggest that any benefits may be relegated to certain sub-groups of premature infants, including infants fed with bovine formula (104856,104868) or those with very low birth weight or extremely low birth weight (104856,104868,104869). These groups seemed to obtain greater benefits than other premature infants or those fed exclusively or almost exclusively with breast milk. Early data from one meta-analysis also suggests that lactoferrin may be more effective at preventing late-onset sepsis when combined with probiotics (104868). Fixed doses of 100-250 mg daily and weight-based doses up to 300 mg/kg daily have been studied (97783,104856,104868,104869,104870). However, many individual clinical studies, including 3 large studies, have failed to demonstrate clear benefits of lactoferrin. These clinical trials, one in very premature infants and the others in very low birthweight infants, show that lactoferrin 150 mg/kg daily, 200 mg/kg daily, or 100 mg daily does not reduce late-onset sepsis when compared with control (104857,104858,110771). Two of these trials had very few infants exclusively fed bovine formula, which may have limited potential benefits. Subgroup analyses from these trials also suggest that extremely low birth weight and/or extremely premature infants may have benefited from lactoferrin (104857,104858).

LIKELY INEFFECTIVE

• Fetal and premature infant mortality. Oral lactoferrin does not reduce the risk of all-cause mortality in premature infants. Details: Many meta-analyses and large clinical trials show that taking lactoferrin does not reduce the risk of mortality from any cause in premature infants (104856,104857,104858,104868,110771).
• Necrotizing enterocolitis (NEC). Most research shows that oral lactoferrin does not reduce the incidence of NEC in premature infants. Details: Many meta-analyses and large clinical studies show that lactoferrin does not reduce the incidence of NEC in premature infants (104856,104857,104858,104868,110771). Exploratory data from one meta-analysis suggest that lactoferrin combined with probiotics may reduce the incidence of NEC when compared with control (104868). However, since probiotics alone have demonstrated benefit for the prevention of NEC in clinical trials, it is unclear if lactoferrin confers any additional benefit.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Oral lactoferrin has only been studied in combination with other ingredients; its effect when used alone is unclear. Details: A large clinical study in adult females with acne shows that taking an oral supplement containing lactoferrin, zinc, niacinamide, and prebiotics once daily for 12 weeks, in addition to applying a topical combination retinoid-based cream, modestly improves the number of acne lesions (i.e., non-inflammatory, inflammatory, and total) when compared with the topical combination retinoid-based cream alone (112915). It is unclear if these effects are due to lactoferrin, other ingredients, or the combination.
• Anemia of chronic disease. Oral lactoferrin might improve hemoglobin levels in some patients with anemia of chronic disease. However, the optimal patient population is unclear. Details: One nonrandomized clinical study evaluated bovine lactoferrin in patients with anemia of chronic disease. In pregnant patients with anemia related to beta-thalassemia or hereditary thrombophilia, taking a specific bovine lactoferrin 100 mg capsule (Lattoglobina, Aqma Italia) twice daily with meals, starting at 6-8 weeks' gestation and continuing until delivery, improves hemoglobin levels by 50% and 15%, respectively, when compared with baseline. In non-pregnant patients, taking this same product twice daily for 30 days improves hemoglobin levels by 18% in patients with hereditary thrombophilia, but not in those with beta-thalassemia. The study may have been inadequately powered to detect a difference from baseline (104865).
• Antibiotic-associated diarrhea. It is unclear if oral lactoferrin is beneficial for preventing antibiotic-associated diarrhea in children or adults. Details: A very small clinical study in long-term care patients shows that adding lactoferrin at an unspecified dose to 600 mL of gastronomy tube solution daily for 56 days reduces the risk for antibiotic-associated diarrhea when compared with placebo (97782). Conversely, a clinical study in children aged 1-18 years receiving antibiotic therapy for an acute respiratory or urinary tract infection shows that those taking bovine lactoferrin 100 mg twice daily are more than twice as likely to develop antibiotic-associated diarrhea during or for the two weeks following antibiotic therapy when compared with those taking placebo (106729). However, the validity of these findings is limited by differences in baseline characteristics between groups.
• Atopic dermatitis (eczema). Oral lactoferrin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in adults with atopic dermatitis shows that taking a combination of lactoferrin 250 mg and a whey derived immunoglobulin-rich fraction 250 mg daily for 56 days improves symptoms in 13 of 22 patients, compared with 4 of 13 patients taking placebo (97789).
• Bacterial vaginosis. Oral lactoferrin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with recurrent bacterial vaginosis shows that adding a specific combination capsule (Respecta, Giellepi Spa Health Science) containing bovine lactoferrin 50 mg and 5 billion colony-forming units of Lactobacillus acidophilus GLA-14 and Lactobacillus rhamnosus HN001 on a varying schedule over 6 months, in conjunction with metronidazole 500 mg twice daily for the first 7 days, reduces the proportion of patients with vaginal discharge by 63%, itching by 57%, and a recurrent episode by 50% when compared with placebo. Patients took 2 capsules daily for 5 days, then 1 capsule daily for 10 days, followed by 1 capsule daily for 10 days of each month, beginning on the first day of the menstrual cycle. It is unclear if these effects are due to lactoferrin, other ingredients, or the combination (104872).
• Chemotherapy-induced anemia. It is unclear if oral lactoferrin is beneficial for chemotherapy-induced anemia. Details: An open-label clinical study in adults with advanced cancer and chemotherapy-induced anemia who are receiving treatment with recombinant human erythropoietin shows that taking oral lactoferrin (Lattoglobina, Grunenthal-Formenti) 200 mg daily for 12 weeks is as effective as intravenous ferric gluconate 125 mg weekly for improving hemoglobin and iron levels (97781).
• Cognitive function. Oral lactoferrin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in healthy adults shows that taking a product containing a combination of lactoferrin 10 mg, probiotics, prebiotics, minerals, and glutathione (Puraflor, GSK Consumer Healthcare, Milano, Italy) daily for 4 weeks does not affect cognitive performance during acute stress when compared with placebo (110923). It is unclear if this effect is due to lactoferrin, other ingredients, or the combination.
• Common cold. It is unclear if oral lactoferrin is beneficial for preventing the common cold. Details: A clinical study in healthy adults shows that taking bovine lactoferrin 200 mg or 600 mg daily for 12 weeks does not reduce the frequency or duration of self-reported symptoms of the common cold when compared with placebo (104859). Another clinical study in adults with frequent colds shows that taking a combination of bovine lactoferrin 400 mg and whey protein immunoglobulin-rich fraction 200 mg daily for 90 days reduces the number of colds by 57% when compared with placebo. There was no effect on cold severity (97786). It is not clear if this effect is due to lactoferrin, whey protein fraction, or the combination.
• Coronavirus disease 2019 (COVID-19). It is unclear if oral lactoferrin is beneficial for the treatment or prevention of COVID-19. Details: A small clinical study in adults hospitalized with mild-to-moderate COVID-19 receiving hydroxychloroquine, vitamin C, zinc, and acetylcysteine shows that taking lactoferrin 200 mg once or twice daily does not improve symptoms when compared with placebo (106731). Similarly, a large clinical study in adults hospitalized with moderate-to-severe COVID-19 receiving standard therapy shows that taking a specific product containing bovine lactoferrin (Mosaic, Pharmaguida) 400 mg twice daily for 30 days does not reduce intensive care unit admission or death, nor improve illness severity scores or discharge within 2 weeks when compared with placebo (112913). However, observational research with this product in outpatient adults with asymptomatic to moderately symptomatic COVID-19 suggests that taking 200-1000 mg daily is associated with a median of 15 days to a negative SARS-CoV-2 test, compared with 24 days in a historical control group (106732). The validity of these findings is limited by the retrospective nature of the study and differences in symptom severity between the groups at baseline. There is also interest in oral lactoferrin for prevention of COVID-19. A large clinical study conducted in healthcare workers in Peru who were screened and tested for COVID-19 shows that taking bovine lactoferrin 600 mg once daily for 65 days does not reduce the number of SARS-CoV-2 cases when compared with placebo (112914). However, the study was stopped prematurely due to vaccine availability; it may not have been powered to detect a difference between groups.
• Diarrhea. It is unclear if oral lactoferrin is beneficial for reducing the incidence of diarrhea in children or adults. Details: A large clinical study in weaned children 12-18 months of age shows that taking bovine lactoferrin 500 mg twice daily for 6 months does not reduce the incidence of diarrhea when compared with placebo (97787). However, a clinical study in infants with anemia who were exclusively breast-fed from 4-6 months before weaning and transitioning to infant formula from 6-9 months shows that fortification of each 100 grams of formula with 38 mg of bovine lactoferrin for 3 months improves vomiting and nausea when compared with formula without fortification. Similarly, fortification of each 100 grams of formula with 76 mg of bovine lactoferrin for 3 months improves diarrhea-related illness, diarrhea, vomiting, and nausea when compared with formula without fortification (106726). Lactoferrin has also been evaluated in adults. A large clinical study in healthy adults working at kindergartens or nursery schools in the winter shows that taking bovine lactoferrin 600 mg daily for 12 weeks is associated with a 1-day duration of diarrhea, compared with 2 days in those taking placebo (106728).
• Gastroenteritis-associated nausea and vomiting. It is unclear if oral lactoferrin prevents the development of gastroenteritis-associated nausea and vomiting in children or adults. Details: A large clinical study in children aged 3-6 years shows that consuming yogurt fortified with bovine lactoferrin 100 mg 3-5 days weekly for 15 weeks reduces the odds of school absence due to vomiting by 19% when compared with consuming the yogurt less than 3 days per week. However, consuming the yogurt did not reduce absences due to gastroenteritis, the presumed cause of vomiting (104862). A large clinical study in healthy adults working at kindergartens or nursery schools in the winter shows that taking bovine lactoferrin 200 or 600 mg daily for 12 weeks is associated with a 12% prevalence of acute gastrointestinal symptoms, compared with a prevalence of 22% in those taking placebo (106728).
• Gingivitis. Oral lactoferrin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in adults with mild gingivitis shows that taking bovine lactoferrin 60 mg, bovine lactoperoxidase 7.8 mg, and glucose oxidase 7.8 mg daily for 12 weeks improves gingival health and plaque index scores when compared with placebo. A lower dose product containing bovine lactoferrin 20 mg, bovine lactoperoxidase 2.6 mg, and glucose oxidase 2.6 mg daily for 12 weeks improves plaque index scores, but not gingival health scores, when compared with placebo. It is unclear if these effects are due to lactoferrin, other ingredients, or the combination (104867).
• Helicobacter pylori. Research on the use of oral lactoferrin as an adjunct for H. pylori eradication is inconclusive and conflicting. Details: Monotherapy with human recombinant lactoferrin, even at high doses of 5 grams daily, does not suppress or eradicate H. pylori infection (13317). However, research on its use as an adjunct to standard therapy is conflicting. Some studies suggest that lactoferrin improves efficacy when added to a triple therapy regimen of rabeprazole, clarithromycin, and tinidazole (13316,13332). However, research using lactoferrin with a triple therapy regimen of esomeprazole, clarithromycin, and amoxicillin found no difference in eradication rates. It is possible that lactoferrin activity on the bacterial cell wall interferes with the cell wall activity of amoxicillin (13315). Other research shows that using lactoferrin in addition to a sequential therapy regimen of esomeprazole, amoxicillin, metronidazole, and clarithromycin or a triple therapy regimen of esomeprazole, amoxicillin, and clarithromycin is associated with eradication rates of 95% or 86%, respectively, compared with eradication rates of 83% and 70%, respectively, with the use of either regimen alone (106730). However, using lactoferrin in addition to a sequential therapy regimen (esomeprazole, amoxicillin, tinidazole, and clarithromycin) and probiotics does not increase eradication more than sequential therapy and probiotics alone (97790).
• Hepatitis C. It is unclear if oral lactoferrin is beneficial for hepatitis C. Details: Some clinical research shows that lactoferrin decreases serum levels of hepatitis C virus RNA and alanine aminotransferase (ALT) in adults with hepatitis C (13320,13321). Some experts recommend starting lactoferrin 1 to 3 months before starting interferon to identify lactoferrin responders (13321,13322,13323,13324). Lactoferrin doses of 1.8 or 3.6 grams daily appear to be necessary for efficacy (13323,13324); lower doses don't seem to have any effect (13313,13314).
• Infant development. Oral lactoferrin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A clinical study in healthy, full-term, exclusively formula-fed infants shows that taking a formula fortified with bovine lactoferrin 0.6 grams/L and bovine milk fat globule membrane 5 grams/L for 12 months improves cognitive development scores by about 8% after 12 months, but not after 18 months, when compared with control formula. This study may have been inadequately powered to detect a difference between groups at 18 months. It is unclear if any effect is due to lactoferrin, milk fat globule membrane, or the combination (104866).
• Iron deficiency anemia. It is unclear if oral lactoferrin is beneficial for the treatment or prevention of iron deficiency anemia in infants and children. Details: An open-label clinical study in children aged 1-10 years with cerebral palsy and iron deficiency anemia shows that taking bovine lactoferrin (Pravotin, Hygint) 100 mg twice daily for 4 weeks improves hemoglobin by 1.4 grams/dL, compared with 0.8 grams/dL in those taking iron hydroxide polymaltose complex providing elemental iron 3 mg/kg twice daily. Lactoferrin also improves serum ferritin, but not the rest of the serum iron profile (106725). Conversely, a small open-label clinical study in children aged 1-18 years with iron deficiency anemia in Egypt shows that the improvement in hemoglobin, serum iron, ferritin, or transferrin saturation is less with lactoferrin 100 mg daily, or twice daily if over age 3, when compared with iron bisglycinate chelate 0.75 mg/kg daily or iron polymaltose complex 6 mg/kg daily for a month. However, improvement in hemoglobin and iron studies was similar when comparing 30% iron saturated lactoferrin (100 mg lactoferrin and 30 mg iron) daily, or twice daily if over age 3 years, with iron bisglycinate chelate or iron polymaltose complex (110189). Lactoferrin has also been evaluated for the prevention of iron deficiency anemia. A clinical study in healthy, full-term formula-fed infants aged 6 weeks to 6 months shows that feeding a low-iron infant formula supplemented with lactoferrin has no effect on iron status or incidence of iron deficiency when compared with the low-iron formula alone (106724).
• Preterm labor. It is unclear if vaginal lactoferrin is beneficial for preventing preterm labor. Details: Observational research in patients diagnosed with bacterial vaginosis in the first trimester of pregnancy and a previous history of preterm labor has found that using a lactoferrin vaginal tablet 300 mg daily for 21 days is associated with a 44% reduced incidence of preterm birth when compared with no intervention. The validity of this study is limited by the use of a retrospective chart review (105405).
• Psoriasis. It is unclear if topical lactoferrin is beneficial in psoriasis. Details: A small open-label clinical study in patients with mild to moderate stable plaque-type psoriasis shows that applying lactoferrin 10% or 20% ointment topically daily in addition to taking bovine lactoferrin 100 mg orally daily (Lattoglobina, Grünenthal-Formenti) for 4 weeks improves symptoms of psoriasis, such as redness and scaling, by up to 37% when compared with use of oral lactoferrin alone (97784).
• Respiratory tract infections. It is unclear if oral lactoferrin is beneficial for treating or preventing respiratory tract infections. Details: A clinical study in healthy children aged 12-32 months shows that taking bovine lactoferrin 48 mg daily for 13 weeks does not reduce symptoms of respiratory tract infections when compared with placebo (104861). However, a clinical study in infants with anemia who were exclusively breast-fed from 4-6 months before weaning and transitioning to infant formula from 6-9 months shows that fortification of each 100 grams of formula with 38 mg of bovine lactoferrin for 3 months improves rhinorrhea, wheezing, and skin rash when compared with formula without fortification. Similarly, fortification of each 100 grams of formula with 76 mg of bovine lactoferrin for 3 months improves respiratory-related illness and wheezing when compared with formula without fortification (106726). There is also interest in oral lactoferrin for prevention of respiratory tract infections. However, two meta-analyses that each included 6 clinical studies in infants, children, and adults who consumed a bovine lactoferrin supplement or bovine lactoferrin enhanced formula, with some studies included in both analyses, have conflicting results. One meta-analysis of 1194 patients shows that lactoferrin reduces the risk of developing a respiratory infection by 43% when compared with placebo or various controls (110774). Conversely, the second meta-analysis of 1157 patients shows that lactoferrin does not reduce the risk of developing a respiratory infection in adults but may reduce the risk by 22% in infants and children when compared with placebo or unenhanced formula (110775). The validity of the findings from these meta-analyses is limited by the heterogeneity of the included studies, which enrolled patients of a broad age range and utilized widely varying dosing regimens. Furthermore, some studies are of poor quality.
• Vaginal candidiasis. Oral lactoferrin has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with recurrent vaginal candidiasis shows that taking a specific combination capsule (Respecta, Giellepi Spa Health Science) containing bovine lactoferrin 50 mg and 5 billion colony-forming units of Lactobacillus acidophilus GLA-14 and Lactobacillus rhamnosus HN001 on a varying schedule over 6 months, in conjunction with clotrimazole 100 mg daily for the first 7 days, reduces the proportion of patients with vaginal discharge by 63%, itching by 100%, and a recurrent infection by 71% when compared with placebo. Patients took 2 capsules daily for 5 days, then 1 capsule daily for 10 days, followed by 1 capsule daily for 10 days of each month, beginning during the premenstrual phase. It is unclear if these effects are due to lactoferrin, other ingredients, or the combination (104863).
• Ventilator-associated pneumonia (VAP). It is unclear if oral lactoferrin is beneficial for preventing VAP. Details: A clinical study in critically ill, mechanically ventilated adults shows that taking lactoferrin 500 mg four times daily for up to 28 days does not reduce the incidence of VAP or other infections, or increase antibiotic-free days, when compared with placebo (104873). More evidence is needed to rate lactoferrin for these uses.

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LIKELY SAFE ...when used orally in amounts commonly found in foods. Beta-glucans derived from oat bran, baker's yeast, or brewer's yeast (Saccharomyces cerevisiae) have Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used orally and appropriately, short-term in medicinal amounts. There is some evidence that yeast-derived beta-glucans 15 grams daily can be used safely for up to 8 weeks (7272). Oat-derived beta-glucans 3-10 grams daily can also be used safely for up to 12 weeks (7272,5796,17129,34700,34727,34729,34765,34766,34811,34812)(34876,107935,109206). ...when used topically and appropriately. A specific beta-glucans serum and emulsion (Awake; Hangzhou Songyang Biotechnical) combination has been used with apparent safely for up to 12 weeks in clinical research (109210). A specific beta-glucans cream (Imunoglukan P4H, PLEURAN s.r.o.) has been used with apparent safety 2-3 times daily for up to 6 months (98201).

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

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LIKELY SAFE ...when used orally in amounts commonly found in foods. Lactoferrin has Generally Regarded as Safe (GRAS) status in the US (13312).

POSSIBLY SAFE ...when used orally in medicinal amounts. Bovine lactoferrin has been safely used at doses of up to 600 mg daily for up to 12 months (13313,13314,13315,13316,13320,13321,13322,13323,97786,104859,104860). Recombinant human lactoferrin has been used with apparent safety at a dose of 5 grams daily for up to 14 days (13317,13318,13319). There is insufficient reliable information available about the safety of lactoferrin when used topically.

CHILDREN: POSSIBLY SAFE
when used enterally in infants and children up to 6 years of age. Lactoferrin has been used safely as a part of enteral feeds in preterm infants at a dose of 250 mg daily or up to 300 mg/kg daily for up to 30 days (97783,97787,104857,104858,104870). Formula fortified with bovine lactoferrin 0.6 grams/L and bovine milk fat globule membrane 5 grams/L has also been used safely in infants for up to 12 months (104866). Bovine and recombinant human lactoferrin 1000 mg daily for up to 6 months has been used with apparent safety in weaned infants up to 18 months of age (97783,97787). Bovine lactoferrin 336-500 mg per week has been used with apparent safety in children 1-6 years of age for 13-15 weeks (104861,104862). There is insufficient reliable information available about the safety of lactoferrin in children over 6 years of age.

PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods. Lactoferrin has Generally Regarded as Safe (GRAS) status in the US (13312).

PREGNANCY: POSSIBLY SAFE
when used orally in medicinal amounts. Lactoferrin has been used with apparent safety during the second or third trimester of pregnancy at doses of up to 250 mg daily for up to 8 weeks (97788). Also, bovine lactoferrin has been used with apparent safety throughout all trimesters of pregnancy at doses of up to 200 mg daily (104865). There is insufficient reliable information available about the safety of intravaginal lactoferrin during pregnancy and lactation; avoid using.

LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods. Lactoferrin has Generally Regarded as Safe (GRAS) status in the US (13312). There is insufficient reliable information available about the safety of lactoferrin when used medicinally during lactation; avoid using.

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ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking beta-glucans with antihypertensive drugs might increase the risk of hypotension.  Details Clinical research shows that taking beta-glucans may reduce systolic and diastolic blood pressure in some hypertensive individuals (34684,34691,34722).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, beta-glucans might interfere with immunosuppressive therapy.  Details Some clinical research shows that beta-glucans have immunostimulant effects (34809,34860,34879,92659,103886,105264).

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General ...Orally and topically, beta-glucans seem to be well-tolerated.
Most Common Adverse Effects:
Topically: Contact dermatitis, skin reactions.

Dermatologic ...Topically, a specific beta-glucans cream r.o.) has been reported to cause skin reactions and contact dermatitis in one clinical trial. These reactions occurred in 27% of patients; reactions were mild and self-limiting in 12% of patients (98201).

Hematologic ...In one clinical trial of children and young adults with neuroblastoma, one of 44 patients developed transient elevations of aspartate transaminase and alanine transaminase within five days of starting oral beta-glucans 120 mg/kg daily (109203).

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General ...Orally, bovine and human recombinant lactoferrin are well tolerated when used in typical doses. However, hjgher doses of 7.2 grams daily increase the risk of side effects and decrease tolerability.
Topically, there is a limited amount of information on the adverse effects of lactoferrin.
Intravaginally, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Constipation, diarrhea, epigastric pain, and nausea.
Topically: Burning sensation.
Serious Adverse Effects (Rare):
Orally: Bowel obstruction, intestinal perforation.

Dermatologic ...Orally, at higher doses of 7. 2 grams daily, lactoferrin has been reported to cause skin rash (13323). Topically, burning sensation has been reported (97784).

Gastrointestinal ...Orally, lactoferrin has been reported to cause diarrhea in some patients. At higher doses of 7.2 grams daily, anorexia and constipation have been reported (13323). However, gastrointestinal effects of lactoferrin, including epigastric pain, constipation, nausea, and diarrhea, are less common than with other sources of iron such as ferrous sulfate (97788). In neonates, single cases of jaundice, bloody stool, bowel obstruction, and intestinal perforation have been reported in clinical trials (104857,104858).

Neurologic/CNS ...Orally, at higher doses of 7. 2 grams daily, lactoferrin has been reported to cause fatigue and chills (13323).

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