Stage 1 Infant Formula

HAPPi Day and Night Milk System

Based on the circadian patterns in mother’s milk

HAPPi Day and Night formulations have been developed based on the scientific evidence that daily circadian fluctuations exist for nutritional components within

human and cow’s milks.1, 4

Milk during the day is characterised by higher levels of cortisol and activity-promoting amino acids during the day, which likely function to promote alertness, feeding behaviour, and catabolic processes in infants. Night Milk is marked by lower levels of these activity-promoting compounds and provides increased levels of melatonin and tryptophan to foster sleep, relax digestion, and support cell restoration.18

There are several reasons why nutritional variation exists between day and night milk including maternal diet, as well as basic physiological variation. However, there is evidence to support the view that some of the variation is more structured and is designed to provide an advantage to infants.

HAPPi Day and Night formulas are nutritionally optimised to reflect an infant’s nutritional needs are different between day and night.

Ingredient and Allergen Declaration

DAY INFANT FORMULA INGREDIENTS:
Milk Solids (Demineralised Whey Powder, Organic Milk (17.6%), Whey Protein Concentrate), Vegetable Oil Blend, Galacto- oligosaccharide (GOS), Lactose, Fructo-oligosaccharide (FOS), Docosahexaenoic Acid Oil (DHA), Arachidonic Acid Oil (ARA), Emulsifiers (Soy Lecithin, Mono- and Di-glycerides), Taurine, Nucleotides (5’-CMP, di Sodium 5’-IMP), Antioxidants (Mixed Tocopherols Concentrate, Ascorbyl Palmitate) Inositol, Lutein. Minerals: [Potassium Chloride, Calcium Carbonate, di Sodium Phosphate, Magnesium Sulphate, Ferric Pyrophosphate, Zinc Sulphate, tri Calcium Phosphate, Copper Sulphate, Manganese Sulphate, Potassium Iodide, Sodium Selenite]. Vitamins: [L-Sodium Ascorbate (Vitamin C), d-alpha Tocopheryl Acetate (Vitamin E), Retinyl Acetate (Vitamin A), Nicotinamide (Vitamin B3), Calcium Pantothenate (Vitamin B5), Colecalciferol (Vitamin D), Thiamin Hydrochloride (Vitamin B1), Riboflavin (Vitamin B2), Pyridoxine Hydrochloride (Vitamin B6), Folic Acid (Vitamin B9), Phytonadione (Vitamin K1), D-Biotin, Cyanocobalamin (Vitamin B12)].

Contains: Milk and Soy. HAPPi Infant formula is based on cow’s milk protein.


NIGHT INFANT FORMULA INGREDIENTS:
Milk Solids (Demineralised Whey Powder, Organic Milk (17.6%), Whey Protein Concentrate), Vegetable Oil Blend, Galacto- oligosaccharide (GOS), Lactose, Fructo-oligosaccharide (FOS), Docosahexaenoic Acid Oil (DHA), Arachidonic Acid Oil (ARA), Emulsifiers (Soy Lecithin, Mono- and Di-glycerides), Tryptophan, Taurine, Nucleotides (di Sodium 5’-UMP, 5’-AMP, di Sodium 5’-GMP), Antioxidants (Mixed Tocopherols Concentrate, Ascorbyl Palmitate) Inositol, Lutein. Minerals: [Potassium Chloride, Calcium Carbonate, di Sodium Phosphate, Magnesium Sulphate, Ferric Pyrophosphate, Zinc Sulphate, tri Calcium Phosphate, Copper Sulphate, Manganese Sulphate, Potassium Iodide, Sodium Selenite]. Vitamins: [L-Sodium Ascorbate (Vitamin C), d-alpha Tocopheryl Acetate (Vitamin E), Retinyl Acetate (Vitamin A), Nicotinamide (Vitamin B3), Calcium Pantothenate (Vitamin B5), Colecalciferol (Vitamin D), Thiamin Hydrochloride (Vitamin B1), Riboflavin (Vitamin B2), Pyridoxine Hydrochloride (Vitamin B6), Folic Acid (Vitamin B9), Phytonadione (Vitamin K1), D-Biotin, Cyanocobalamin (Vitamin B12)].

Contains: Milk and Soy. HAPPi Infant formula is based on cow’s milk protein.

Nutrition

  • Average quantity per 100 mL of Prepared Formula  
    Energy 284 kJ
    Protein  1.53 g
      – Whey 0.94 g
    Fat – Total 3.72 g
     – Omega-3 78.5 mg
      α-Linolenic Acid (ALA) 70.5 mg
      Docosahexaenoic Acid (DHA) 7.98 mg
     – Omega-6 567 mg
      Linoleic Acid  559 mg
      Arachidonic Acid  7.98 mg
    Carbohydrate  6.84 g
       
    Vitamins  
    Vitamin A  66.5 ug RE 
    Vitamin B6  49.8 ug  
    Vitamin B12  0.27 ug 
    Vitamin C  9.98 mg
    Vitamin D3  0.94 ug 
    Vitamin E 1.33 mg αTE
    Vitamin K 5.32 ug 
    Biotin 2.26 ug 
    Niacin 478 ug
    Folate  13.3 ug 
    Pantothenic Acid  385 ug
    Riboflavin 166 ug 
    Thiamin 66.5 ug 
       
    Minerals  
    Calcium  50.5 mg
    Copper 53.2 ug
    Iodine  8.00 ug
    Iron 0.73 mg
    Magnesium  5.59 mg
    Manganese 6.65 ug
    Phosphorus  30.6 mg
    Selenium 1.60 ug
    Zinc  0.56 mg
    Chloride 46.6 mg
    Potassium 73.2 mg
    Sodium 22.6 mg
       
    Additional Nutrients  
    Lutein  12.0 ug
    Choline 13.3 mg
    Inositol 3.99 mg
    Prebiotic  
     – Galacto-oligosaccharide (GOS) 395 mg
     – Fructo-oligosaccharide (FOS) 132 mg
    Nucleotides  
    – Cytidine 5′-monophosphate (CMP) 0.68 mg
    – Inosine 5′-monophosphate (IMP) 0.36 mg
    Tryptophan^   25.1 mg
    ^Naturally Occurring Amount  
  • Average quantity per 100 mL of Prepared Formula  
    Energy 284 kJ
    Protein  1.53 g
      – Whey 0.94 g
    Fat – Total 3.72 g
     – Omega-3 78.5 mg
    α-Linolenic Acid (ALA) 70.5 mg
    Docosahexaenoic Acid (DHA) 7.98 mg
     – Omega-6 567 mg
      Linoleic Acid  559 mg
      Arachidonic Acid  7.98 mg
    Carbohydrate  6.84 g
       
    Vitamins  
    Vitamin A  66.5 ug RE 
    Vitamin B6  49.8 ug 
    Vitamin B12  0.27 ug 
    Vitamin C  9.98 mg
    Vitamin D3  0.94 ug 
    Vitamin E 1.33 mg αTE
    Vitamin K 5.32 ug 
    Biotin 2.26 ug 
    Niacin 478 ug
    Folate  13.3 ug 
    Pantothenic Acid  385 ug
    Riboflavin 166 ug 
    Thiamin 66.5 ug 
       
    Minerals  
    Calcium  50.5 mg
    Copper 53.2 ug
    Iodine  8.00 ug
    Iron 0.82 mg
    Magnesium  5.59 mg
    Manganese 6.65 ug
    Phosphorus  30.6 mg
    Selenium 1.60 ug
    Zinc  0.56 mg
    Chloride 46.6 mg
    Potassium 73.2 mg
    Sodium 22.6 mg
       
    Additional Nutrients  
    Lutein  12.0 ug
    Choline 13.3 mg
    Inositol 3.99 mg
    Prebiotic  
     – Galacto-oligosaccharide (GOS) 395 mg
     – Fructo-oligosaccharide (FOS) 132 mg
    Nucleotides  
    – Uridine 5′-monophosphate (UMP) 0.74 mg
    – Adenosine 5′-monophosphate (AMP) 0.60 mg
    – Guanosine 5′-monophosphate (GMP) 0.32 mg
    Tryptophan – Total  30.6 mg

Dilutions & Preparation

Product Benefits

Our products are based on over 200 years of scientific research that explores the circadian rhythm² ³. In humans, this is the natural  internal process that regulates the body’s ability to sleep at night and be alert during the day.

Greater understanding of the circadian science of cow’s milk and human milk composition has led to the identification of key nutrients that display these circadian cycles¹ ⁴. These important nutrients provide key support for a child’s brain function and cognitive development.

Tryptophan: Greater levels in night milk

In the newborn, tryptophan and its metabolites are essential to brain maturation and to the development of neurobehavioral regulations of food intake, satiation and sleep-wake-rhythm. A blood-brain transfer of tryptophan occurs as a precursor of its metabolite’s serotonin and melatonin⁵. Like melatonin, tryptophan levels rise and fall according to a circadian rhythm, with concentrations peaking at night¹. The use of tryptophan in dissociated day/night infant milk formulas has been shown to support and improve infantile development of sleep/wake rhythms⁶.

Iron: Greater levels in night milk

The dietary iron requirement for newborns, infants and during early childhood is high. Iron is an essential nutrient involved in the production of new red blood cells and is crucial for brain development and cognitive function. ​
Iron consistently shows circadian variation in concentration with the peak of the rhythm occurring during the evening¹ ¹⁴.​

Nucleotides: Day and night oscillations

Nucleotides are found in human milk and display notable circadian oscillations. 5′CMP, and 5′IMP peak during daylight hours while research shows concentrations of two nucleotides, 5’UMP, 5’AMP are highest in human milk during the night and thought to be associated with its sleep promoting action. While 5′UMP did not show a clear circadian rhythm, there was an increase in its levels at night.​

Nucleotides are necessary for DNA and participate in cellular signalling and metabolic processes within cells. Several clinical studies have reported beneficial effects of nucleotide supplementation on gut microflora, diarrhoea and immune function¹⁰ ¹³.​

Sleep-wake cycles in infants fed a day/night dissociated formula

In a prospective study of 30 infants, a daytime formula was used during the hours of 6 a.m to 6 p.m. It contained low levels of tryptophan, and some of the nucleotides that are present at high levels in human milk during the day. A night-time formula was used from 6 p.m to 6 a.m. It had higher levels of tryptophan and of a different set of nucleotides that are present in human milk during the night.

This day/night formula was associated with a significant reduction (p<0.05) in sleep latency (the time a child takes to fall asleep after being placed in a crib) and a significant increase (p<0.05) in the hours of actual sleep¹⁶ ¹⁷.

References

  1. Italianer, M.F et al.  Circadian Variation in Human Milk Composition, a Systematic Review. Nutrients 202012, 2328. ​
  2. Honma, S. The mammalian circadian system: a hierarchical multi-oscillator structure for generating circadian rhythm. J Physiol Sci 68207–219 (2018).​
  3. Rong-Chi Huang. The discoveries of molecular mechanisms for the circadian rhythm: The 2017 Nobel Prize in Physiology or Medicine, Biomedical Journal, Volume 41, Issue 1 (2018).​
  4. Z.W. Teng et al. Effects of the circadian rhythm on milk composition in dairy cows: Does day milk differ from night milk?, Journal of Dairy Science, Volume 104, Issue 7, 8301-8313, (2021).​
  5. Gabriel Manjarrez, PhD* et al. Free Tryptophan as an Indicator of Brain Serotonin Synthesis in Infants PEDIATRIC NEUROLOGY Vol. 18 No. I 1988​
  6. Sara Aparicio, Celia Garau, Susana Esteban, María C. Nicolau, Montserrat Rivero & Rubén V. Rial (2007) Chrononutrition: Use of dissociated day/night infant milk formulas to improve the development of the wake–sleep rhythms. Effects of tryptophan, Nutritional Neuroscience, 10:3-4, 137-143​
  7. Manja Fleddermann, et al. Role of selected amino acids on plasma IGF‑I concentration in infants Eur J Nutr (2017) 56:613–620​
  8. Tetsuo Harada, Masaaki Hirotani, Mari Maeda, Hiromi Nomura and Hitomi Takeuchi, Correlation between Breakfast Tryptophan Content and Morningness–Eveningness in Japanese Infants and Students Aged 0–15 yrs, Harada, T et al. J Physiol Anthropol, 26: 201–207, 2007.​
  9. Michael w. Yogman, M.D., M.Sc., And steven h. Zeisel, m.D., Ph.D., Diet and sleep patterns in newborn infants, The New England Journal of Medicine, Vol. 309 No. 19, 2010.​
  10. Sánchez CL, Cubero J, S á nchez J, Chancl ó n B, Rivero M, Rodríguez A, et al. The possible role of human milk nucleotides as sleep inducers. Nutr Neurosci. 2009;12:2 – 8.​
  11. Yu VY. Scientific rationale and benefits of nucleotide supplementation of infant formula. J Paediatr Child Health. 2002 Dec;38(6):543-9.​
  12. Singhal A, et al (2010). Dietary nucleotides and early growth in formula-fed infants: a randomized controlled trial. Pediatrics. 2010 Oct;126(4):e946-53
  13. Sánchez, C.L.Human milk nucleotides improve sleep: A focus on circadian profiles. In Handbook of Nutrition, Diet and Sleep; Wageningen Academic Publishers: Wageningen, The Netherlands, 2013.​
  14. Picciano MF, Guthrie HA. Copper, iron, and zinc contents of mature human milk. Am J Clin Nutr. 1976 Mar;29(3):242-54. ​
  15. Yao M, Lien EL, Capeding MR, Fitzgerald M, Ramanujam K, Yuhas R, Northington R, Lebumfacil J, Wang L, DeRusso PA. Effects of term infant formulas containing high sn-2 palmitate with and without oligofructose on stool composition, stool characteristics, and bifidogenicity. J Pediatr Gastroenterol Nutr. 2014 Oct;59(4):440-8.
  16. Cubero J, Narciso D, Aparicio S, Garau C, Valero V, Rivero M, et al. Improved circadian sleep-wake cycle in infants fed a day/night dissociated formula milk. Neuro Endocrinol Lett. 2006;27:373 – 80.
  17. Cubero J, Narciso D, Terr ó n P, Rial R, Esteban S, Rivero M, et al. Chrononutrition applied to formula milks to consolidate infants ’ sleep/wake cycle. Neuro Endocrinol Lett. 2007;28:360 –6.
  18. Hahn-Holbrook J, Saxbe D, Bixby C, Steele C, Glynn L. Human milk as “chrononutrition”: implications for child health and development. Pediatr Res. 2019 Jun;85(7):936-942.