NiMera Day and Night infant formula based on research of changes to milk due to circadian rhythm
Background
Human milk has been shown to alter its composition, depending on time of day (Hahn-Holbrook, 2019). For mothers who exclusively breast feed, this may not seem so relevant, however for those who pump breast milk, or who utilise infant formula to feed their baby, this information is important, and may influence their feeding regime.
Whilst infant formula can’t replicate human milk, research into improving infant formula leads to breakthroughs to improve its composition and nutritional value to infants. Understanding the circadian rhythm of the feeding of the breast fed infant assisted the latest breakthrough, which will help ensure that nutrition for formula fed infants is optimised. Human milk is a dynamic fluid, changing its formulation based on circadian rhythms, and assisting with baby’s sleep, whereas cows milk, which most infant formulas are based on, is relatively static in nature (Lien, 2003, Hahn-Holbrook, 2019, Cubero, 2007). For this reason, formulation of NiMera, which more closely follows the changes seen in human milk during the day and night will likely result in helping infants receive the right nutrients at the right times, resulting in the right nutrients to support development and improved sleep/wake cycle in bottle fed infants.
Tryptophan
Tryptophan is an essential amino acid. It is a precursor of the neurotransmitter serotonin and of the hormone melatonin (Cubero, 2007). Oral consumption of tryptophan modifies the circulating levels of serotonin and melatonin, with absorption dependent on presence of carbohydrate. Adequate carbohydrate results in easier absorption of tryptophan, and transport into the brain. Numerous papers have shown that formulas designed with these factors in mind improve sleep/wake cycles in infants (Cubero, 2007; Cubero 2006; Lien, 2003).
Tryptophan is regarded as one of the limiting amino acids in low-protein infant formula products (1.3% protein or lower) (Heine, 1995). This means that if the protein level in a standard whey based infant formula is lowered to reach the same level of protein as human milk, this results in low tryptophan levels, amongst other amino acids (Heine, 1994). The amino acid balance within the infant formula must be carefully formulated when working at lower protein levels, as is required of infant formula.
The milk whey fraction, α-lactalbumin, has a relatively high concentration of tryptophan. One study of low-protein infant formulas showed that a tryptophan level of 2.1%, delivered a serum level in infants fed infant formula that did not differ significantly from an exclusively breast-fed control group of infants and has been used to improve the amino acid profile in infant formulas (Heine, 1996).
NIMERA’S QUANTITIES ARE IN LINE WITH RESEARCH WHICH HAS SHOWN THAT PROVIDING NUTRIENTS AT THE CORRECT TIMES CORRELATES WITH IMPROVED SLEEP/WAKE CYCLES IN INFANTS AND SUPPORT THE INFANTS DEVELOPMENT
Tryptophan/Serotonin Pathway
Increasing tryptophan in infant formula will have a significant benefit in providing the right nutrients to support the infants’ development and the sleep/wake cycles. This is due to producing a similar plasma level of tryptophan to that of breast-fed infants (Lien, 2003; Heine, 1996; Cubero, 2007); there is a well-established link between intake of tryptophan in breast milk, and sleep patterns of breast fed infants. This is based upon the synthesis of melatonin from tryptophan through the tryptophan/serotonin pathway (Richard, 2009).
When examining the overall cycle of tryptophan in breast milk, lowest levels are found mid-afternoon. Tryptophan in breast milk peaks at around 3am. This affects 6-sulfatoxymelatonin, a metabolite of melatonin, which subsequently peaks approximately 3 hours later in breast fed infants. The rhythm of this metabolite seems to be influenced by the rhythm of tryptophan found in breast milk (Cubero, 2005). As is expected, the level of melatonin itself is highest overnight, dropping during the day.
From this evidence, an infant formula that is higher in tryptophan for night-time would elicit the most beneficial impact on infant sleep. Two studies have confirmed this, with different formulations; one for day time consumption (6:00 am to 6:00pm) and the other for night time consumption (6:00pm to 6:00am). The use of separate formulations for day and night time consumption was shown to “consolidate the sleep/wake rhythm in bottle-fed infants” (Cubero, 2007).
NiMera’s two separate formulas, for day and night mirror this, with 176mg of tryptophan per 100g in day time formula, and 293mg per 100g in the night time formula, along with 60g and 56g of carbohydrate per 100g in the day and night formula, respectively. These quantities are in line with research which has shown that providing nutrients at the correct times correlates with improved sleep/wake cycles in infants and support the infants development (Cubero 2007, Cubero 2006).
Varying composition of milk
Human milk is a powerful form of chrononutrition, formulated by evolutionary processes to communicate time-of-day information to infants. Human milk contains higher levels of cortisol and activity-promoting amino acids during the day, to promote alertness, feeding behaviour, and catabolic processes in infants. Night milk contains high levels of melatonin and tryptophan to foster sleep, relax digestion, and support cell restoration (Sanchez, 2013, Hahn-Holbrook, 2019). Development of NiMera is formulated around the basis of these changes, and the importance of providing particular nutrients at certain times of day or night, to more closely replicate human breast milk.
Human milk protein has been shown to contain a relatively high concentration of tryptophan, compared with other mammalian milks, such as cows’ milk and goats’ milk. In formula, tryptophan is the limiting amino acid. α-lactalbumin is a protein that is rich in tryptophan. In human milk, the concentrations of α-lactalbumin are much larger than cow milk or whey-dominant formula (Lien, 2003).
As a result, NiMera has been developed with lower protein but higher tryptophan concentrations due to elevated α-lactalbumin.
NIMERA HAS TAKEN ON FINDINGS IN DEVELOPMENT OF THEIR DAY AND NIGHT INFANT FORMULATIONS TO MATCH WHAT HAS SHOWN TO BE EFFICACIOUS IN RESEARCH
Other Nutrients of Note
Other nutrients of interest include a number of nucleotides, due to their varied presence in day and night formulas in research studies (Cubero 2006, Cubero, 2007). Nucleotides are compounds that play a key role in numerous intracellular chemical processes. They are made by the body, though are frequently added to infant formulas due to the important role they play in DNA and RNA; components of co-enzymes NAD, FAD and coenzyme A; as biological regulators and as an energy source. Studies have also shown potential benefits to intestinal flora, immunity, iron absorption, lipid metabolism and gut development (Lerner & Shamir, 2000). Whilst in traditional formulas, levels do not vary due to the presence of a single formulation only. With adenosine 5′-monophosphate and uridine 5′-monophosphate being components of the night time formula, whilst Cytidine 5′-monophosphate, Guanosine 5′-monophosphate and inosine 5′-monophosphate are all found in the day time, or activity promoting formula (Cubero, 2006).
NiMera has taken on these findings in development of their day and night infant formulations to match what has shown to be efficacious in research, and assist with promoting improved sleep/wake cycles in bottle fed infants and support the infants development (refer to table of nutrient levels).
Table A: Summary of Key Nutrients for NiMera Day and NiMera Night infant milk formulas
Nutrient – Stage 1
Amino Acid
Tryptophan mg
Nucleotides
Adenosine 5'-monophosphate mg
Cytidine 5'-monophosphate mg
Guanosine 5'-monophosphate mg
Inosine 5'-monophosphate mg
Uridine 5'-monophosphate mg
Total Nucleotides mg
Nimera Day per 100mL of prepared feed (mg)
0
25.0
0
0.00
1.07
0.19
0.35
0.00
1.61
Nimera Night per 100mL of prepared feed (mg)
0
41.0
0
0.67
0.00
0.00
0.00
0.92
1.59
HELPING INFANTS RECEIVE THE RIGHT NUTRIENTS, AT THE RIGHT TIMES IS IMPERATIVE WHEN IT COMES TO OPTIMISING SLEEP CYCLES, AND ENERGY THROUGH THE DAY. NIMERA DAY AND NIGHT FORMULAS MEET AUSTRALIAN REGULATORY REQUIREMENTS.
Regulatory requirements
The makers of NiMera have worked to ensure that their products meet Australian regulatory requirements, particularly in relation to protein content of infant formula.
In Australia and New Zealand, the level of tryptophan in infant formula products is required to be a minimum of 7mg/100kJ (Schedule 29–6) (FSANZ, 2020). For a formula that is 280kJ/100mL, this translates to 19.6mg/100mL.
The protein content of infant formula is required to be between 0.45g/100kJ and 0.7g/100kJ (FSANZ, 2020b). Again, for a 280kJ/100mL formula, this translates as 1.26g – 1.96g protein/100mL. So the minimum amount of tryptophan within the protein of a 280kJ/100mL formula will range from 1.0% up to 1.6% of the total protein. This contrasts with typical levels of tryptophan within human milk as around 1.9-2.3% of the protein (Heine, 1994).
NiMera’ two separate formulas, for day and night provide 25.0mg of tryptophan per 100mL of prepared feed in day time formula, and 41.0mg of tryptophan per 100mL of prepared feed in the night time formula (refer to table of nutrient levels). This equates to significantly more tryptophan than the required minimum 7mg per 100kJ or 19.6mg per 100mL of prepared feed for a formula that is 280kJ/100mL.
Protein totals 0.5-0.7g in both the day and night formula per 100kJ, with the night time formula being slightly higher protein. This equates to protein of 1.5g and 1.9g per 100mL of prepared feed in day and night formula respectively.
Nutrient – Stage 1
Amino Acid
Tryptophan mg
Regulatory Compliance Range per 280kJ/100mL
≥19.6
NiMera Day per 100mL of prepare feed
25.0
NiMera Night per 100mL of prepare feed
41.0
Why is this important?
Helping infants receive the right nutrients, at the right times is imperative when it comes to optimising sleep cycles, and energy through the day. Ask any new parent, and getting their baby’s sleep ‘right’ is a high priority when it comes to helping adjust to the significant changes that come with becoming a parent. Developing a positive sleep routine is not just essential for the baby, but for the parents as well.
Positive sleep habits start from birth. Babies who do not get enough sleep may have trouble functioning during the day. At night, they may find it hard to settle. Taking steps to help support baby’s circadian rhythms through appropriately timed feeds can help set them up early on for a positive sleep routine, which can significantly impact their long term development and health (Cespedes, 2015).
In adults, inadequate sleep is associated with increased risk of obesity, diabetes and mental health conditions. Conversely, a positive sleep routine can help optimise health across the life.
NiMera was created with the intent to develop the best milk powder products for infants, toddlers and adults. We combine the best ingredients for our day and night formulations to support development and growth during the day and better sleep during the night.
