Bioactive Milk Peptides by Life Extension

LIKELY EFFECTIVE

• Atopic dermatitis (eczema). Consuming casein peptide as part of formula with or without breastmilk for up to 6 months reduces the risk of atopic dermatitis in infants. Details: Clinical research shows that feeding infants a casein peptide-based formula (Nutramigen or Progestimil, Mead Johnson), with or without breastmilk for 4-6 months, reduces the risk for atopic dermatitis during the first 9-24 months of life by 52% to 73% when compared to cow's milk formula (91655,91656,91658). The benefits of casein peptides appear to be most significant in infants with a family history of atopy (91655,91656). Additionally, the benefit of using a casein peptide-based formula during the first 4 months of life persists into childhood, with a 29% reduced risk of developing atopic dermatitis at 6 years of age when compared to cow's milk formula (91659,91660). Clinical research also shows that casein peptide formula is equally effective to hydrolyzed whey protein formula for reducing the risk for atopic dermatitis in infants (91657,91658,91659,91660,91661).
• Atopic disease. Consuming casein peptide as part of formula during the first 4 months of life reduces the risk of atopic disease in infants with a family history of atopy. The benefits of casein peptide in infants without a family history of atopy is unclear. Details: Clinical research in infants with a family history of atopy shows that taking a casein peptide-based formula (Nutramigen, Mead Johnson) during the first 4 months of life, or after weaning from breastmilk, reduces the risk for atopic manifestations during the first 12-18 months of life by 39% to 44% when compared with cow's milk formula (91656,91658). This benefit persists over time, with a 20% reduced risk for developing atopic disease at 6 years of age when compared to cow's milk formula (91660). However, it may not be beneficial in children without a family history of atopy. One large, ancillary clinical study in children at increased risk for development of type 1 diabetes, but not specifically at risk for atopy, shows that using an extensively hydrolyzed casein peptide formula (Nutramigen, Mead Johnson) in infancy for up to 6-8 months does not prevent persistent asthma, allergic rhinitis, or atopic dermatitis development when compared with using a conventional formula containing 80% intact cow's milk protein and 20% hydrolyzed milk protein (Enfamil, Mead Johnson). The validity of these findings is limited by the patient population and the unclear duration of follow up (106564).
• Food allergies. Consuming casein peptide formulas is a safe alternative to cow's milk in children with cow's milk allergy. Details: Clinical research shows that specific casein peptide formulas are a safe and well-tolerated alternative for children with documented allergy to cow's milk. Evaluated formulas include Alimentum (Abbot Laboratories), Damira 2000 (Nutrition & Sante S.L.), Frisolac Allergycare (Friesland Nutrition), and Nutramigen (Mead Johnson) (91663,91664,91665,111439). A cost-effective analysis in children with cow's milk allergy also suggests that using casein peptide-based formula is cost-effective dominant and reduces other allergic manifestations when compared with soy-based formula (111438).

POSSIBLY EFFECTIVE

• Colic. Clinical research shows that consuming casein peptides as part of formula reduces crying, short-term, in infants with colic. Details: Clinical research in infants with colic shows that replacing cow's milk formula with a specific casein peptide formula (Nutramigen, Mead Johnson) significantly reduces crying and colic when compared with cow's milk formula. However, this effect appears to diminish after more than four days of use (91262). Preliminary clinical research shows that consuming specific casein peptide formulas (Alimentum, Abbot Laboratories; Nutramigen, Mead Johnson) for 7 days reduces daily crying time by up to 5 hours and reduces crying intensity when compared with baseline in infants with colic (91264). The validity of this finding is limited by the lack of a comparator group.
• Diabetes. Consuming casein peptides with carbohydrates may be beneficial for reducing postprandial glucose and insulin levels in adults with type 2 diabetes. Casein peptides have also been evaluated for the prevention of type 1 diabetes in infants, with inconclusive results. Details: In adults with type 2 diabetes, casein protein may improve postprandial glucose levels. Most clinical research shows that consuming casein peptides in conjunction with a carbohydrate bolus increases postprandial insulin response by 26% to 300% and reduces postprandial glucose levels by 5% to 28% when compared with consuming carbohydrates alone (91276,91295,91297,91299). These effects seem to persist with casein peptide doses as low as 12 grams daily, but not 6 grams daily (91300). Preliminary clinical research also shows that adding leucine 5 grams or 0.1 grams/kg to casein peptides increases postprandial insulin levels by 52% to 200%, reduces postprandial glucose levels by 5% to 12%, and improves 24-hour glucose levels by 11% when compared with consuming carbohydrates alone (91296,91297). However, some preliminary clinical research shows that consuming casein peptides 0.4 grams/kg with each meal for one day does not improve glycemic control (91298). These differing outcomes might be related to the forms of carbohydrates used, which include carbohydrate boluses and carbohydrate-containing meals. Additionally, the evidence for the effects of intact casein protein, as opposed to casein peptides, on postprandial insulin and glucose levels is conflicting (91276,91299). Clinical research in infants 6-8 months of age who are genetically predisposed to type 1 diabetes shows that administering a specific casein peptide-based formula (Nutramigen, Mead Johnson) in place of breastmilk decreases the development of one or more diabetes-associated auto-antibodies when compared with cow's milk formula. However, there was no difference in type 1 diabetes incidence after 10 years. This study was not powered to detect a difference in this outcome (91675).
• Hypertension. The casein peptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), sometimes referred to as lactotripeptides, can modestly reduce blood pressure in patients with hypertension. Lower doses given for shorter durations seem to produce greater effects, and the effects may be more pronounced in Japanese patients than in European patients. Details: The most comprehensive meta-analysis to-date in patients with hypertension shows that taking casein peptides reduces systolic blood pressure (SBP) by 3 mmHg and diastolic blood pressure (DBP) by 1.5 mmHg. The average dose of casein peptides was 10.5 mg daily, including IPP 5.2 mg and VPP 5.3 mg daily, for about 8 weeks. However, there may be an inverse dose-response relationship; daily doses of casein peptides of 10 mg or less, lasting for 8 weeks or less, reduced blood pressure to a greater degree when compared with higher doses given for longer durations. Furthermore, casein peptides produced by fermentation resulted in modestly greater blood pressure reduction when compared with casein peptides produced by enzymatic hydrolysis (103765). Patient ethnicity may also play a role in the magnitude of effect. Other meta-analyses show a 1-6 mmHg reduction in SBP and 0.6-1.5 mmHg reduction in DBP when compared with control (103762,103763,103765,111437). A small clinical study in healthy Japanese males and postmenopausal adults with prehypertension shows that supplementation with casein peptides IPP 2 mg and VPP 1.4 mg daily for 8 weeks reduces home-monitored 7-day mean DBP, but not SBP, by 0.9 mmHg, compared with an increase of 1.2 mmHg in those receiving placebo (106565). Although findings are positive overall, the validity of the above meta-analysis, as well as older or less comprehensive analyses, is limited by the poor reporting and methodology of the included studies (103763,103765,103770,103772). Some limited research in patients with metabolic syndrome shows conflicting blood pressure lowering effects. A small clinical study shows that taking IPP/VPP (Calpis Co., Ltd.) 10.2 mg in the morning before breakfast daily for 4 weeks lowers 24-hour ambulatory systolic blood pressure by 2 mmHg, but not diastolic blood pressure, when compared with placebo (103764). However, another study shows that taking casein peptides 5-25 mg daily with plant sterols 2 grams daily orally for 12 weeks does not reduce blood pressure when compared with placebo (103767). Notably, this study was not adequately powered to detect small changes in blood pressure.
• Neonatal jaundice. Clinical research suggests that consuming casein peptide reduces the risk of jaundice in neonates. Details: Preliminary clinical research shows that feeding newborns a specific casein peptide formula (Nutramigen, Mead Johnson) for 3 weeks reduces the risk of jaundice when compared with whey-predominant formula (91642) or human milk (91642,91651). Other preliminary clinical research in breastfed newborns shows that taking 5 mL of casein peptide formula, created by enzymatic hydrolysis, 6 times daily for 7 days decreases transcutaneous bilirubin levels when compared with breastfeeding alone (91643).

POSSIBLY INEFFECTIVE

• Asthma. Consuming casein peptide does not appear to reduce the risk of asthma in infants. Details: Most clinical research shows that feeding infants a casein peptide-based formula (Nutramigen or Progestimil, Mead Johnson), with or without breastmilk for 4 months, does not reduce the risk for asthma in the first 4 months to 6 years of life in children with a family history of atopy (91655,91659,91660). However, one preliminary clinical study shows that feeding infants Nutramigen beginning at about 3.8 months of age decreases wheezing by 61% compared to cow's milk formula; the incidence of asthma was not evaluated (91656).
• Infant development. Consuming casein peptide does not appear to affect growth or development in healthy infants, or in premature or low-birth weight infants. Details: Most clinical research shows that using casein peptide-predominant formula for 6 weeks to 6 months in premature, low-birth weight, or healthy infants does not affect growth when compared with breast milk, whey protein-based formula, rice hydrolysate formula, cow's milk formula, or amino acid-based formula (86085,91644,91672,91673). Additionally, feeding infants a specific casein peptide formula (Nutramigen, Mead Johnson) for 4 months does not affect growth at 6 or 10 years when compared with whey protein-based formula, cow's milk formula, or breast milk (86085,91644). However, clinical research suggests that a casein peptide-based formula might be beneficial in infants with cow's milk allergy. One study in this population shows that casein peptide-based formula significantly increases growth from 6-12 months of age when compared with soy-based formula (91672).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. It is unclear if oral casein peptides are beneficial in patients with acne. Details: Preliminary clinical research in adults with moderate to severe acne shows that taking a specific casein peptide (Lactium) 150 mg orally daily for 84 days does not reduce acne lesion count when compared with control. However, the study may have been inadequately powered to detect a difference between groups (111436).
• Aging skin. It is unclear if oral casein peptides are beneficial in patients with aging skin. Details: A small clinical study in healthy, normotensive older Japanese adults shows that taking casein peptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) orally once daily for 48 weeks reduces facial pigmentation area by about 15%, compared with an increase of about 6% in patients taking placebo (106563).
• Anxiety. Although there has been interest in using oral casein peptides for anxiety, there is insufficient reliable information about the clinical effects of casein peptides for this purpose.
• Athletic performance. It is unclear if oral casein peptides are beneficial for athletic performance. Details: Preliminary clinical research in overweight male police officers shows that taking casein peptides 1.5 grams/kg orally daily in two divided doses for 12 weeks, in conjunction with resistance training, decreases body fat percentage by 3%, increases lean body mass by 2 kg, and improves chest, shoulder, and leg press strength by around 30% when compared with whey protein (85648).
• Cancer. Although there has been interest in using oral casein peptides for cancer, there is insufficient reliable information about the clinical effects of casein peptides for this purpose.
• Diarrhea. It is unclear if oral casein peptides are beneficial in patients with diarrhea. Details: Preliminary clinical research in male children with persistent diarrhea shows that consuming a casein peptide-based diet during hospitalization is less effective for reducing stool output than a yogurt-based diet (91648).
• Epilepsy. Although there has been interest in using oral casein peptides for epilepsy, there is insufficient reliable information about the clinical effects of casein peptides for this purpose.
• Exercise-induced muscle soreness. It is unclear if oral casein peptides are beneficial in patients with exercise-induced muscle soreness. Details: Preliminary clinical research in male cyclists shows that drinking 200 mL of a carbohydrate beverage containing 1.8% casein peptides every 5 km followed by 500 mL after cycling completion reduces exercise-induced muscle soreness and improves late-exercise time-trial performance when compared with drinking a carbohydrate beverage alone (91256).
• Fatigue. Although there has been interest in using oral casein peptides for fatigue, there is insufficient reliable information about the clinical effects of casein peptides for this purpose.
• Hyperlipidemia. Low quality research suggests that oral casein peptides are not beneficial in patients with hyperlipidemia. Details: A meta-analysis of randomized trials in subjects with and without hyperlipidemia shows that using casein peptide-based diets for 1-48 weeks does not improve low-density lipoprotein cholesterol, high-density cholesterol, or triglyceride levels when compared with control (111437).
• Insomnia. It is unclear if oral casein peptides are beneficial in patients with insomnia. Details: A small clinical study in Korean patients with poor sleep quality shows that taking a specific product (Lactium, Ingredia) containing bovine alpha-s1 casein peptides 300 mg one hour before bedtime for 4 weeks modestly improves sleep efficiency based on subjective reports and actigraphy measures when compared with placebo (103774). Casein peptides have also been studied as part of combination products. A small clinical study in adults with insomnia or disturbed sleep patterns shows that a specific product (RLX2; LiveLife Biosciences AG) containing a specific casein peptide, alpha-s1-casein tryptic hydrolysate, 150 mg, and L-theanine 50 mg, taken one hour before bedtime for 4 weeks, increases sleep duration by 45 minutes and improves habitual sleep efficiency and daytime dysfunction when compared with baseline. However, it does not affect blood pressure, heart rate, or cortisol levels (108556). It is unclear if these effects are due to L-theanine, alpha-s1-casein tryptic hydrolysate, or the combination.
• Physical performance. It is unclear if oral casein peptides are beneficial for physical performance. Details: Preliminary clinical research in healthy older males shows that taking casein peptides 10 grams before and after resistance training for 8 weeks does not improve strength or body composition when compared with placebo (91255).
• Stress. Although there has been interest in using oral casein peptides for stress, there is insufficient reliable information about the clinical effects of casein peptides for this purpose. More evidence is needed to rate casein peptides for these uses.

(Read more about CASEIN PEPTIDES)

LIKELY SAFE ...when used orally and appropriately. Casein peptides have been safely used in clinical trials lasting up to 5 months (85648,103763,103764,103765,103770,103772).

CHILDREN: LIKELY SAFE
when used orally and appropriately. Casein peptide formulas have been safely used in healthy, premature, and very low birth weight infants (91262,91264,91643,91673,91675).

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

(Read more about CASEIN PEPTIDES)

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = B Theoretically, combining these casein peptides with antihypertensive drugs might increase the risk of hypotension.  Details Clinical research shows that some casein peptides, including the lactotripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), can modestly reduce blood pressure in patients with hypertension (103763,103765,103770,103772).

(Read more about CASEIN PEPTIDES)

General ...Orally, casein peptides are well tolerated in infants and adults. Adverse effects reported in clinical trials did not occur more frequently than with placebo.

(Read more about CASEIN PEPTIDES)