N ATURE OF THE A PPLICATION
Basis of the Application
The Applicant sought to eliminate subclause 23(d) from Standard 2.9.1 of the Code, which mandates that when long chain polyunsaturated fatty acids (LCPUFAs) are added to infant and follow-on formulas, the omega 6 to omega 3 LCPUFA ratio must be approximately 2.
Assessment, the Applicant modified their original Application so that it now seeks an amendment of subclause 23(d) such that if LCPUFAs are added to infant formula the omega
6 to omega 3 LCPUFAs must be present in a ratio of a minimum of one
The Applicant believes that recent scientific evidence indicates that the previously required ratio of omega 6 to omega 3 in infant formula is no longer necessary when long-chain polyunsaturated fatty acids (LCPUFA) are included.
The Applicant also contends that subclause 23(d) could represent a technical barrier to trade because no proposed international legislation or existing overseas legislation requires such a ratio.
However, the Applicant’s position has changed due to a further shift in the scientific debate on LCPUFA additions to infant formula, notably at an international level.
Scope of Application
This Application pertains solely to infant formula and follow-on formula Infant formula and follow-on formula are defined in Standard 2.9.1 as follows:
Infant formula - means an infant formula product represented as a breast milk substitute for infants and which satisfies the nutritional requirements of infants aged up to four to six months
Follow-on formula is an infant formula designed as a substitute for breast milk or standard infant formula, serving as the primary liquid nourishment for infants from six months of age onward, as they transition to a more varied diet.
This Application does not affect ‘infant formulas for special dietary use’ (e.g formulas for premature infants and/or those with specific medical conditions)
Clauses 25 and 27(1) of Standard 2.9.1 already provide infant formulas for special dietary use with an exemption from Clause 23(d), by allowing manufacturers to specifically formulate these products to meet unique medical requirements Therefore, the Applicant’s request will not impact on the current regulatory requirements for these products
This Application also excludes ‘formulated supplementary foods for young children’ (i.e a formulated supplementary food for children aged one to three years) otherwise known as
For the purpose of this Report, the term ‘infant formula’ relates to both infant formula and follow-on formula.
B ACKGROUND
Current Standard
Standard 2.9.1 of the Code regulates the compositional and labelling requirements of infant formula products 4,5 Subclause 23(d) of Standard 2.9.1 states:
The definition of long-chain polyunsaturated fatty acids (LCPUFA) varies in scientific literature, but according to Standard 2.9.1 of the Code, LCPUFA are specifically defined as fatty acids with a chain length exceeding 20 carbon units.
2 Simmer, K (2001) Longchain polyunsaturated fatty acid supplementation in infants born at term
Cochrane.Database.Syst.Rev (4):CD000376.
3 Mahan, K and Escott-Stump, S (2000) Krause's Food, Nutrition and Diet Therapy 10th ed,
Infant formula, as outlined in Standard 2.9.1, refers to a product derived from milk or other edible food components, whether from animal or plant sources, that provides sufficient nutrition to be the primary liquid nourishment for infants.
5 ‘Infant formula products’ refers to all food regulated by Standard 2.9.1
The fats in infant formula and follow-on formula must –
Infant formulas or follow-on formulas should maintain a ratio of approximately 2:1 between total long-chain omega-6 series fatty acids and total long-chain omega-3 series fatty acids.
In addition, the Table to clause 23 prescribes maximum limits for omega 6 LCPUFA, omega
3 LCPUFA and AA of 2%, 1% and 1% of total fatty acids respectively.
The European Union has updated its regulations on infant formula, specifically regarding the optional inclusion of long-chain polyunsaturated fatty acids (LCPUFAs) According to Clause 5.7 of Annex 1 in the European Commission's Infant Formula Directive (2006/141/EC), when LCPUFAs are voluntarily added to infant formula and follow-on formula, the DHA content must not surpass the total amount of omega-6 LCPUFAs present.
Codex Alimentarius is finalizing a draft standard for infant formula, which mandates that if DHA is included, an equivalent amount of AA must also be added However, this requirement does not apply to follow-up formulas, which are governed by a separate standard.
Aside from European Union and Codex Alimentarius, there are no other overseas or international requirements specific to the LCPUFA contents of infant formula.
Current Market
In Australia and New Zealand, a variety of infant formulas enriched with LCPUFAs are widely accessible, offered by four leading brands These brands provide options both with and without added LCPUFAs Notably, two of the brands are produced in New Zealand using locally sourced milk powder, while the other two brands are manufactured internationally and imported into both countries.
In Australia and New Zealand, the term 'gold' in infant formula product titles signifies formulas enriched with added LCPUFAs and sometimes other optional ingredients like nucleotides These gold-labeled formulas are priced higher than those without LCPUFAs Recent grocery retail sales data reveals that gold products are among the best-selling infant formulas, with one gold product achieving the top sales rank in Australia.
In July 2007, a draft standard is set to be presented to the Codex Alimentarius Commission for ratification, which includes a crucial clause stipulating that when docosahexaenoic acid (DHA) is incorporated into infant formula, the levels of arachidonic acid (ARA) must be at least equal to those of DHA.
7 Ranking Report for Grocery Retail, National AZTEC Information Systems, August 2006
It is preferable for companies to manufacture one formulation for worldwide distribution, for cost advantage purposes However, it appears that products made in or imported into
Australia and New Zealand exclusively sell certain products due to specific manufacturing practices, particularly the required ratio of added long-chain polyunsaturated fatty acids (LCPUFAs) This necessity for compliance not only contributes to the increased cost of these products but also restricts their availability in markets beyond Australia and New Zealand.
Historical Background
Prior to the development of the joint Code, there was no regulation on the addition of
The inclusion of long-chain polyunsaturated fatty acids (LCPUFAs) in infant formula is permitted under the previous regulations in Australia and New Zealand This addition typically involves incorporating fish oil as an ingredient in the formulation of infant formula.
A Proposal was raised to both harmonise and update the regulation of infant formula within Australia and New Zealand, titled Proposal P93 – Review of Infant Formula At the
In the Preliminary Inquiry Stage of Proposal P93, the requirements for adding long-chain polyunsaturated fatty acids (LCPUFAs) were aligned with the maximum levels set by the European Commission and the United Kingdom, which were the only regulations specific to LCPUFAs for infant formula at that time Notably, these overseas regulations did not include a specified omega-6 to omega-3 ratio.
The inclusion of a specific omega 6 to omega 3 LCPUFA ratio in infant formula is supported by findings from the United States Life Sciences Research Office (LSRO), which indicated that varying intakes of these fatty acids can affect infant metabolism differently A particular concern arose from studies showing that adding DHA alone to infant formula may lead to reduced serum levels of AA Consequently, based on research involving preterm infants and animal studies, the LSRO recommended the careful consideration of this fatty acid ratio in infant nutrition.
Inappropriate levels of long-chain polyunsaturated fatty acids (LCPUFAs) may jeopardize clinical outcomes, especially concerning growth in infants Consequently, the Life Sciences Research Organization (LSRO) advised against the inclusion of docosahexaenoic acid (DHA) and arachidonic acid (AA) in infant formulas in 1998, with plans to reevaluate this decision within five years.
To address safety concerns regarding the omega-6 and omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) already permitted through fish oil ingredients, the Proposal P93 Preliminary Inquiry Report recommended establishing a strict omega-6 to omega-3 LCPUFA ratio of 2:1 This ratio was derived from analyses of human milk Although this measure was acknowledged as inconsistent with international regulations, it was deemed essential for mitigating potential risks to vulnerable populations.
Public consultation revealed feedback indicating that the omega 6 to omega 3 LCPUFA ratio in human milk is not consistently two As a result, the requirement for this ratio has been maintained, but it has been adjusted to state 'approximately 2'.
8 Australian Food Standards Code, up to Amendment 53 These regulations are no longer in force.
9 New Zealand Food Regulations 1984, up to Amendment 10 These regulations are no longer in force.
10 Forsyth, J.S (1998) Lipids in Infant Formulas Nutr Res Revs 11:255-278
T HE P ROBLEM
According to Standard 2.9.1 of the Code, when long-chain polyunsaturated fatty acids (LCPUFAs) with carbon chains greater than 20 are voluntarily included in infant formula, they should maintain an omega 6 to omega 3 LCPUFA ratio of approximately 2:1 The Applicant notes that there are no existing natural ingredients for infant formula, including human breast milk, that offer this specific 2:1 ratio of arachidonic acid (AA) to docosahexaenoic acid (DHA).
The Applicant aims to modify the omega 6 to omega 3 LCPUFA ratio requirement for infant formula, citing recent scientific evidence They emphasize the importance of aligning domestic and international food standards, arguing that the existing ratio requirement of approximately 2 could create technical trade barriers for manufacturers and importers in Australia and New Zealand.
O BJECTIVES
In developing or varying a food standard, FSANZ is required by its legislation to meet three primary objectives that are set out in section 10 of the FSANZ Act These are:
the protection of public health and safety;
the provision of adequate information relating to food to enable consumers to make informed choices; and
the prevention of misleading or deceptive conduct.
In developing and varying standards, FSANZ must also have regard to:
the need for standards to be based on risk analysis using the best available scientific evidence;
the promotion of consistency between domestic and international food standards;
the desirability of an efficient and internationally competitive food industry;
the promotion of fair trading in food; and
any written policy guidelines formulated by the Ministerial Council.
The specific objectives for the assessment of this Application are to:
protect the public health and safety of formula-fed infants; and
promote consistency between domestic and international food standards.
K EY A SSESSMENT Q UESTIONS
The key assessment questions considered at Draft Assessment are:
What is the range of LCPUFA ratios naturally occurring in human milk, and how do these ratios compare to the omega 6 to omega 3 LCPUFA ratio prescribed in Standard 2.9.1?
Are there any differences in the growth and development of infants fed formulas with varying ratios of omega 6 to omega 3 LCPUFA?
What are the risks associated with feeding infants formula containing the singular addition of DHA or AA?
A risk assessment at Draft Assessment has evaluated the potential risks associated with altering the omega 6 to omega 3 LCPUFA ratio from 2, addressing key assessment questions outlined in Section 5 The analysis specifically focuses on the impact of formulas featuring varying omega 6 and omega 3 ratios.
LCPUFA on infant growth and development The fatty acid profile of human milk and the impact on serum fatty acid levels has also been assessed.
This risk assessment includes a thorough review of existing literature on the incorporation of LCPUFAs into infant formula To ensure an objective evaluation of the evidence, the assessment has been peer-reviewed by experts Professor William McLean from Ohio State University and Dr Clare Wall from Massey University.
The following section summarises the risk assessment’s literature review and subsequent analysis and conclusions The full details of the risk assessment can be found at Attachment 2.
R ISK A SSESSMENT S UMMARY
FSANZ reviewed 16 randomized controlled trials on the impact of LCPUFA-enriched infant formula on term infants, focusing on omega 6 to omega 3 LCPUFA ratios ranging from 0.3 to 4.3 The analysis excluded studies that incorporated only omega 3 LCPUFAs into the formula These trials aimed to assess the influence of dietary omega 6 and omega 3 LCPUFAs on infant growth and development.
Research from 16 studies indicates that infant formulas with different levels of added omega-6 and omega-3 LCPUFAs show minimal differences in growth and cognitive outcomes Specifically, anthropometric data reveals no significant impact of LCPUFA addition on infant growth compared to standard formulas However, the inclusion of LCPUFAs does seem to have a slight positive effect on the development of visual acuity in infants relative to standard formulations.
The fatty acid profile of human milk exhibits considerable variation in the omega 6 to omega 3 long-chain polyunsaturated fatty acid (LCPUFA) ratios across different geographical regions, indicating that infants can adapt to significant differences in this ratio in their milk sources.
Research indicates that variations in the omega-6 and omega-3 LCPUFA levels in infant formulas have minimal impact on infant growth and development Additionally, the current evidence is insufficient to draw conclusive comparisons between the effects of adding DHA alone versus the combined addition of DHA and AA in infant formulas.
Due to the minimal influence of LCPUFAs on infant growth and development, it is concluded that there is little advantage from using one particular omega 6 to omega 3
LCPUFA ratio over another when LCPUFAs are voluntarily added to infant formula.
At Draft Assessment, FSANZ has considered the management of any risks identified through the risk assessment and submissions received during the public consultation period.
S AFETY , EFFICACY AND OPTIMAL INTAKES
FSANZ's risk assessment suggests that the amounts of added omega-6 and omega-3 LCPUFAs in infant formula are not expected to affect infant growth and development Evidence indicates that infants can withstand considerable fluctuations in the omega-6 to omega-3 LCPUFA ratio found in these formulas.
FSANZ's risk assessment analyzed studies that utilized omega 6 to omega 3 LCPUFA ratios between 0.3 and 4.3, deeming this range suitable Additionally, the assessment found no safety concerns for formula-fed infants when the omega 6 to omega 3 LCPUFA ratio is adjusted from the approximate value of 2.
To enhance infant formula, it is advisable to include both AA and DHA simultaneously, as there is uncertainty about the effects of adding DHA alone compared to the combination of DHA and AA.
Many submitters advocated for altering the current omega 6 to omega 3 ratio of approximately 2 in infant formula containing LCPUFA Additionally, there was a consensus among many that there is inadequate evidence to confirm the safety of adding LCPUFA in isolation.
The inclusion of an upper limit for DHA and AA also maintains a level of safety with
LCPUFA additions to infant formula The Code currently sets maximum levels for various LCPUFAs if these are added to infant formula (Standard 2.9.1 Table to Clause 23).
C ONSISTENCY WITH INTERNATIONAL REGULATIONS
The updated Codex standard for infant formula states that if DHA is included, the levels of AA should match or exceed those of DHA Additionally, it notes that national authorities can adjust these guidelines based on specific nutritional needs, suggesting that LCPUFA-enriched infant formulas with varying omega 6 to omega 3 ratios are deemed safe and appropriate for infants.
The European Union revised ruling, Commission Directive 2006/141/EU on infant formula and follow-on formula, includes a requirement that the DHA content shall not exceed the content of omega 6 LCPUFA
Several submitters highlighted that the current omega 6 to omega 3 LCPUFA ratio requirement of approximately 2 is not aligned with international standards Additionally, industry representatives pointed out that the specific ratio requirement for Australia and New Zealand imposes trade barriers and increases costs for both manufacturers and consumers.
Amending the omega 6 to omega 3 LCPUFA ratio requirement from approximately 2 to a minimum of 1, in accordance with the maximum levels established in Standard 2.9.1, would align with international standards and recommendations, thereby promoting trade facilitation.
O PTIONS
Option 1 – Maintain status quo
To uphold the current regulations, it is essential to keep the Code unchanged, ensuring that the ratio of omega-6 to omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) in infant formula remains approximately 2:1.
Option 2 – Amend Standard 2.9.1
Amend Standard 2.9.1 to establish that the omega 6 to omega 3 LCPUFA ratio in infant and follow-on formula must be no less than 1 when LCPUFAs are included, replacing the existing requirement of approximately 2.
I MPACT A NALYSIS
Affected Parties
This application impacts several key parties, including consumers, specifically formula-fed infants who consume infant formula enriched with LCPUFAs and their caregivers Additionally, it affects the industry, comprising manufacturers and importers of infant formula in Australia and New Zealand, as well as government enforcement agencies in both countries.
Cost-Benefit Analysis
This analysis assesses the immediate and tangible impacts of the current food standard under Option 1 and the proposed amendment under Option 2.
Maintaining the current situation will have little effect on consumers, as infant formula enriched with LCPUFAs will remain accessible Consequently, parents of formula-fed infants will still have the option to choose these products and potentially benefit from their nutritional advantages.
The cost of infant formula enriched with LCPUFAs is expected to remain higher than that of standard formulas due to the specific omega 6 to omega 3 LCPUFA ratio required for Australia and New Zealand Industry experts warn that if these elevated prices deter consumers, products may be withdrawn from the market, leading to decreased competition This reduction in competition could result in even higher prices for LCPUFA-supplemented formulas, making them unaffordable for many consumers.
The current regulations may restrict the availability of formula options for infants, as they impose barriers to importing products that do not comply with the Code, ultimately reducing consumer choice.
Maintaining the status quo would continue to impact on industry as it is inconsistent with international recommendations and regulations.
Australia and New Zealand's unique requirement for an omega 6 to omega 3 LCPUFA ratio of around 2 creates a significant cost burden for the infant formula industry This financial strain is likely to be transferred to consumers, as manufacturers face higher production costs for formulas that meet these specific regulations Additionally, industry stakeholders argue that prescriptive ratios impose challenges for local manufacturers who also export to regions with less stringent regulations.
If consumers reject a product due to its higher price, it may lead to decreased competition in the marketplace, potentially resulting in these products being withdrawn from circulation.
Maintaining the current ratio requirement could create a technical barrier to trade, as it conflicts with international regulations This inconsistency affects the distribution of certain infant formulas that are designed for global markets.
Australia and New Zealand is considered a minor market within this global trade Therefore the industry experiences difficulties from having to manufacture products with added
LCPUFAs that are suitable for both local and export markets
The absence of alignment with international regulations and manufacturing standards increases the costs and complexities associated with importing infant formula products in Australia and New Zealand Importers often face challenges in ensuring compliance with the Code, which may lead to a limited selection of infant formulas enriched with LCPUFAs available in these markets.
Maintaining the current regulations regarding the omega 6 to omega 3 LCPUFA ratio in infant formula is expected to have a minimal impact on the Australian and New Zealand Governments' monitoring and enforcement efforts.
Requiring an omega 6 to omega 3 ratio of at least 1, instead of approximately 2, is unlikely to significantly affect the health and safety of infant formula consumers Research suggests that growth and development are not heavily influenced by the specific amounts of added omega 6 and omega 3 LCPUFAs Infant formulas containing these beneficial long-chain polyunsaturated fatty acids will still be available, ensuring that formula-fed infants can continue to receive the potential advantages of these essential nutrients.
Maintaining an omega 6 to omega 3 LCPUFA ratio of at least 1 not only complies with international regulations but also expands trade opportunities, potentially leading to a broader variety of products for consumers.
Manufacturers of infant formula could benefit from cost savings by producing a single formulation for global distribution, which may lead to lower prices for consumers.
To align with the recent Codex recommendations and the European Union Directive, industries should adjust the omega 6 to omega 3 LCPUFA ratio from the current approximate ratio of 2 to a minimum requirement of 1.
Manufacturing a single formulation for global distribution offers significant cost benefits for companies producing infant formula As production expands beyond Australia and New Zealand, the higher costs linked to meeting current regulatory requirements are expected to decrease.
Importers in Australia and New Zealand could face fewer challenges when importing products that adhere to regulatory codes By adopting Option 2, manufacturers could lower costs and simplify the process of importing infant formula, enabling a broader selection of products to be available in the market.
Locally produced infant formula can effectively cater to both domestic and international markets, minimizing trade barriers and potentially boosting sales to countries beyond Australia and New Zealand.
C OMPARISON OF O PTIONS
A review of the Draft Assessment options shows that Option 1 effectively safeguards the health and safety of formula-fed infants, as research supports that a ratio of omega 6 to omega 3 long-chain polyunsaturated fatty acids (LCPUFA) around 2 is deemed acceptable.
Research indicates that the ratios of long-chain polyunsaturated fatty acids (LCPUFAs) in breast milk can differ significantly, and infants are capable of withstanding considerable variations in the omega-6 to omega-3 LCPUFA ratio in their milk source Therefore, there seems to be no added advantage in recommending a specific omega ratio for infants.
The unique omega 6 to omega 3 LCPUFA ratio requirement of approximately 2 in Australia and New Zealand creates inconsistencies with international food standards, leading to trade barriers and higher manufacturing and purchasing costs This ratio not only restricts the variety of products available to consumers but also suggests that the costs associated with maintaining it outweigh any potential benefits.
Option 2 ensures the health and safety of formula-fed infants by maintaining a safe omega 6 to omega 3 LCPUFA ratio of at least 1 Research suggests that the growth and development of infants are unlikely to be significantly affected by the specific amounts of LCPUFAs present.
A ratio of at least 1 aligns with international food standards, offering advantages in manufacturing, trade, and cost-efficiency for the food industry, which could ultimately benefit consumers.
A comparison of options indicates Option 2 provides greater net benefits than Option 1
C ONSULTATION AND C OMMUNICATION
Initial Assessment
During the six-week public consultation from May 31 to July 12, 2006, FSANZ received 42 submissions, including 11 in response to the Initial Assessment Report A comprehensive summary of these submissions and the issues raised is available in Attachment 3.
Submitters’ views were mixed in relation to a preferred regulatory option However, the majority supported a change to the current ratio requirement
Of the public health and academic submitters (8) a majority favoured the retention of a ratio requirement, with more recommending a 1:1 ratio in preference to the current ratio of approximately 2.
A majority of industry submitters (12) expressed support for changing the current requirements in the Code, although opinions varied on whether to maintain a ratio or remove sub-clause 23(d) from Standard 2.9.1 Among those favoring the retention of a ratio, the 1:1 ratio was the most popular choice Additionally, some submitters proposed an alternative omega-6 to omega-3 LCPUFA ratio specifically for follow-on formula intended for infants over six months of age.
Three government submitters expressed support for various options, including maintaining the current status quo, adopting Option 2, and establishing a new omega 6 to omega 3 LCPUFA ratio that differs from the existing requirement of approximately 2.
The preferred option of the two consumer submitters differed, but neither supported retaining the status quo.
Draft Assessment
FSANZ is now seeking comment in relation to this Draft Assessment Report Comments received in response to this report will be used to assist in the development of a Final
Submitters are invited to provide comment in relation to issues discussed in this report and the proposed regulatory options, and potential impacts in relation to these options.
World Trade Organization (WTO)
As WTO members, Australia and New Zealand must inform other member nations when their proposed mandatory regulatory measures conflict with existing or upcoming international standards, especially if these measures could significantly impact trade.
To align Australian and New Zealand food standards with EU infant formula regulations and the draft Codex infant formula standard, it is proposed to amend Standard 2.9.1 of the Code by adjusting the omega 6 to omega 3 LCPUFA ratio from approximately 2 to a minimum of 1.
Eleven submissions were received from university students, primarily from the Food Science program at the University of Auckland, New Zealand The majority of these submissions expressed support for Option 2, advocating for the elimination of the existing clause that mandates a ratio of approximately 2.
The anticipated changes aim to align Australian and New Zealand regulations with existing and future international standards, ensuring they do not create trade barriers Consequently, member nations of the WTO will not be informed about the proposed amendment to Standard 2.9.1 under the Technical Barriers to Trade or Sanitary and Phytosanitary Agreements.
C ONCLUSION AND P REFERRED A PPROACH
The preferred regulatory approach for Application A532 is Option 2, which proposes an amendment to Standard 2.9.1 This amendment mandates that if long-chain polyunsaturated fatty acids (LCPUFAs) are included in infant formula, the ratio of omega-6 to omega-3 LCPUFAs must be no less than 1.
The considerations made in reaching this preferred approach are as follows:
the change to the omega 6 to omega 3 LCPUFA ratio does not pose any health and safety risks to formula-fed infants;
Option 2 aligns with existing and proposed international regulations, which would lower trade barriers, enhance product availability, and decrease costs for both industries and consumers.
overall, affected parties will receive a net-benefit from Option 2.
FSANZ therefore recommends the proposed draft variation(s) to the Code that are provided in Attachment 1.
I MPLEMENTATION AND R EVIEW
After the consultation period concludes, a Final Assessment of the Application will be conducted and presented for approval by the FSANZ Board The decision made by the FSANZ Board will subsequently be communicated to the Ministerial Council.
Following notification, the proposed draft variation to the Code is expected to come into effect on gazettal, subject to any request from the Ministerial Council for a review of
A532 summary of submissions from the initial assessment report
Introduction
On 27 February 2004, FSANZ received a joint Application from the Infant Formula Manufacturers Association of Australia and the New Zealand Infant Formula Marketers’ Association, seeking to amend Standard 2.9.1 – Infant Formula Products of the Australia New Zealand Food Standards Code The proposed amendment aims to modify the existing omega 6 to omega 3 long chain polyunsaturated fatty acid (LCPUFA) ratio of approximately 2 in infant formulas that contain added LCPUFAs.
FSANZ has conducted a comprehensive review of existing literature regarding the addition of long-chain polyunsaturated fatty acids (LCPUFAs) to term infant formula This assessment aims to evaluate how varying ratios of omega-6 and omega-3 LCPUFA in infant formula impact the growth and development of infants.
In undertaking this assessment, literature has been sourced from the following locations:
PubMed electronic databases, using the search terms ‘infant formula AND long chain AND growth’ and ‘infant formula AND long chain AND development’; and
Primary research material from review articles by Makrides et al (2000a), Makrides et al (2005), and Fleith and Clandinin (2005).
FSANZ has refined its evidence base by excluding studies on pre-term infants, those that initiated formula intervention beyond two weeks after birth, and studies lacking assessments of anthropometric, visual acuity, or behavioral parameters This approach guarantees that the evidence specifically focuses on the health outcomes associated with the addition of LCPUFAs to formulas intended for term infants.
A total of twenty-two published articles were identified through the specified search strategies, encompassing the findings of sixteen distinct studies, with multiple articles addressing various aspects of the same research.
All trials evaluated the effects of LCPUFA-enriched formulas against standard infant formulas, which were commercially available products compliant with the regulations at the time of the study.
allocation to different formula types was random and double-blinded in all trials; and
In studies evaluating visual acuity and neurological development, the parental educational level and socioeconomic status remained consistent across all groups, whereas these data were not gathered in studies focused solely on anthropometric endpoints.
The findings of 16 studies, detailed in Tables A1-A5, highlight the significance of incorporating LCPUFAs into infant formula, emphasizing the potential benefits for infant development.
12 Consistent with Standard 2.9.1 of the Code, this report classifies LCPUFAs as polyunsaturated fatty acids with a chain length of > 20 carbon units.
Findings of studies on the addition of LCPUFAs to infant formula
FSANZ identified 16 studies that primarily compared various infant formulas over time, focusing on those with added docosahexaenoic acid (DHA) alone or in combination with arachidonic acid (AA) The AA to DHA ratios in these studies ranged from 0.3:1 to 4.3:1.
Ten studies incorporated a non-randomised group of breast-fed infants alongside formula-fed groups, highlighting potential maternal variables such as IQ, education level, and socioeconomic status that could influence outcomes Despite these variables, breast-fed infants serve as a crucial reference in infant feeding research (Birch et al., 2007) While this report does not aim to evaluate the overall effectiveness of infant formula compared to human milk, the findings related to human milk are discussed for their relevance in understanding infant nutrition.
2.1 The impact on infant growth
Thirteen of the 16 studies reported assessments of infant growth parameters, e.g weight, length, or head circumference Nearly all of these studies show that the addition of
The inclusion of long-chain polyunsaturated fatty acids (LCPUFAs) in infant formula does not impact growth outcomes when compared to standard formula This holds true whether the formula contains only DHA or a combination of DHA and AA in different ratios.
Three articles (Agostoni et al., 1994; Lapillonne et al., 2000; Morris et al., 2000) did report a significant difference in either weight or head circumferences In two of these articles
According to Agostoni et al (1994) and Morris et al (2000), significant differences between study groups were observed only at birth, with no effects of diet noted at 4 and 12 months These initial differences may indicate issues with the randomization processes in the studies, but they are more likely attributed to the small sample sizes, which were 23 for Agostoni et al and approximately 55 for Morris et al.
Lapillonne et al (2000) found a significant difference in mean head circumference of 1.4 cm (p0.05) (Auestad et al., 2003).
4 Analysis of the findings on omega 6 and omega 3 LCPUFA addition to infant formula
A review of 16 studies indicates that there is minimal variation in growth and neurological outcomes among infants fed formulas with different levels of added omega-6 and omega-3 LCPUFAs Anthropometric data reveal no consistent diet-related effects from these additions However, some research suggests that LCPUFAs may positively impact infants' visual development compared to standard formulas, while other studies report no significant improvements in visual acuity.
However, there are exceptions to the visual and neurological development trends that warrant further discussion.
A notable study by Auestad et al (2001) found no improvement in visual acuity from LCPUFA-enriched formula compared to standard formula, utilizing the largest sample size (n = 177) among similar studies, which enhances its statistical power The researchers addressed common methodological issues by implementing an analysis of variance to minimize errors from multiple examination centers and by using two different sources of LCPUFA ingredients to ensure the reliability of their findings Despite contradicting positive results from earlier studies (Makrides et al., 1995a; Birch et al., 1998; Hoffman et al., 2000; Birch et al., 2005), the quality controls in Auestad et al.'s research make their conclusions highly reliable.
An important exception in respect to neurological development is the study by Scott et al
A study by Scott et al (1998) found that 14-month-old infants fed formula containing only DHA had lower vocabulary production scores compared to those fed formula with both DHA and AA This finding contrasts with previous research on neurological development Birch et al (2000) suggested that the DHA concentration in the DHA-only formula (0.23% by weight) may have been insufficient, as other studies typically used at least 0.35% Additionally, the variability in results could be attributed to the use of multiple examiners in the cognitive tests Birch et al also proposed that Scott et al.'s unique methodology might have revealed effects on a less-explored area of cognition, making it difficult to compare with other studies.
Overall, the quality of research within the evidence base on omega 6 and omega 3 LCPUFA addition to infant formula is high The main deficiencies encountered can be summarised as:
Many studies on feeding regimes have small sample sizes, with most involving fewer than 20 subjects per group Only three studies have included over 150 subjects in total (Carlson et al., 1999; Lucas et al., 1999; Auestad et al., 2001) This limited sample size reduces the statistical power of the evidence, leading to greater uncertainty in the findings.
Variations in linoleic acid (8.37-34.2% wt) and alpha-linolenic acid (0.7-5.0% wt) levels in test formulas may lead to inconsistent outcomes when adding DHA and AA, as these fatty acids serve as precursors for their synthesis.
Inconsistencies in the ages for testing, and in the methodologies used to assess study endpoints.
The lack of correction for baseline anthropometric data.
Despite some limitations, evidence indicates that adding LCPUFAs to infant formula has a negligible effect on infants' growth and development The primary potential advantage of LCPUFA supplementation seems to be an enhancement in visual acuity development, although existing data on this outcome remains inconsistent Additionally, assessments show no significant impact on infant growth and development from variations in omega-6 and omega-3 LCPUFA levels in infant formulas.
Current evidence on the effects of adding only DHA versus both DHA and AA to infant formula is limited, making it difficult to draw definitive conclusions Available data indicate that the addition of DHA alone is equally effective as the combination of DHA and AA, with no significant impact—positive or negative—on infant growth and development.
Other relevant issues
5.1 Systematic reviews of LCPUFA addition to term infant formula
FSANZ has identified several systematic reviews of the literature on the addition of
Meta-analyses have examined the impact of LCPUFA-enriched infant formula on growth and development, revealing that such formulas do not significantly affect infant growth Despite varying study selections and focuses, the findings indicate insufficient evidence to support a positive influence of LCPUFAs on visual and neurological development in infants.
5.2 Human milk omega 6 and omega 3 LCPUFA content
The Australia New Zealand Food Standards Code prescribes an omega 6 to omega 3
The recommended LCPUFA ratio for infant formula is approximately 2, based on the assumption by the Life Sciences Research Office (Raiten et al., 1998) that the omega 6 to omega 3 LCPUFA ratio in human milk is relatively stable However, recent studies indicate that this assumption may not hold true.
Research from 20 studies on human milk across various geographical regions indicates that arachidonic acid (AA) levels remain relatively stable, while docosahexaenoic acid (DHA) levels exhibit significant variability This variability in DHA, combined with differing maternal dietary patterns and lactation stages, leads to a wide fluctuation in the omega-6 to omega-3 long-chain polyunsaturated fatty acid (LCPUFA) ratio in human milk.
Research indicates that infants from both developing and developed countries can adapt to considerable differences in the omega 6 to omega 3 LCPUFA ratio present in their milk sources, highlighting the resilience of their nutritional needs across diverse geographical contexts.
Research indicates that using DHA as the sole source of added long-chain polyunsaturated fatty acids (LCPUFAs) in infant formula leads to notably lower levels of arachidonic acid (AA) in the red blood cells of infants, in comparison to those fed standard infant formula (Auestad et al., 1997; Makrides et al., 2005).
However, the singular addition of DHA ensures that an infant’s red blood cell DHA levels remain at a similar or even higher level than those of breast-fed infants
Research indicates that the addition of arachidonic acid (AA) with docosahexaenoic acid (DHA) can help maintain red blood cell AA levels comparable to those found in breast-fed infants (Fleith and Clandinin, 2005).
The absence of omega-6 or omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) in infant formulas significantly affects the DHA and AA levels in infants However, the impact of different AA to DHA ratios in these formulas on infant growth and development remains uncertain A study by Auestad et al (1997) indicated that infants receiving a formula with DHA alone experienced a decrease in AA status compared to those receiving both DHA and AA.
AA group, however the serum AA data were not cross-referenced with the study’s growth and development outcomes.
C ONCLUSION
Studies by FSANZ indicate that adding long-chain polyunsaturated fatty acids (LCPUFAs) to infant formula does not significantly affect infant growth and has only a minimal and variable impact on visual and neurological development The evidence suggests that any influence on growth and development is not likely related to the amounts of omega-6 and omega-3 LCPUFAs included in the formula Additionally, it remains unclear whether formula containing only DHA has different effects on infants compared to formulas that include both DHA and AA However, current findings indicate that the singular addition of DHA to infant formula does not lead to any adverse health effects.
There does not, therefore, appear to be any advantage from using one particular omega 6 to omega 3 LCPUFA ratio over another within the range of 0.3:1 to 4.3:1, or even from adding
Table A1: Methodology and design of studies on the LCPUFA content of infant formulas (0-12 months of age)
Infant Dietary Regime n Omega 6 LCPUFA (% wt)
Randomisation into control and LCPUFA formula groups
Breast-fed infants were used as a matched negative control
Randomisation, intervention and assessment were blinded.
Assessment of weight, height and head circumference at 4 months.
Assessment of Brunet-Lezine test at 4 and 24 months.
Randomisation into control and LCPUFA formula groups
Randomisation, intervention and assessment were blinded.
0-12 months Assessment of weight, height and head circumference at 4 and 12 months (Auestad et al., 1997).
Assessment of visual acuity at 4, 6 and
Assessment of Bayley Scales of Infant Development at 12 months (Scott et al., 1998).
Groupings Infant Dietary Regime Details*
Infant Dietary Regime n Omega 6 LCPUFA (% wt)
Randomisation into control and LCPUFA formula groups
Randomisation, intervention and assessment were blinded.
Assessment of weight, height and head circumference at 4, 6 and
Assessment of visual acuity at 2, 4, 6 and
Assessment of Bayley Scales of Infant Development at 6 and 12 months.
Randomisation into control and LCPUFA formula groups
Intervention and assessment were blinded.
Assessment of weight, height and head circumference at 4, 6 and
Assessment of visual acuity at 4, 6 and
Assessment of Bayley Scales at 18 months.
Birch et al (2005) Randomisation into control and LCPUFA formula groups
Randomisation, intervention and assessment were blinded.
12 months Assessment of visual acuity at 4 and 12 months.
Assessment of stereoacuity at 4, 10 and
Groupings Infant Dietary Regime Details*
Infant Dietary Regime n Omega 6 LCPUFA (% wt)
Randomisation into control and LCPUFA formula groups
Randomisation, intervention and assessment were blinded.
Assessment of weight, height and head circumference at 4 and 12 months.
Assessment of visual acuity at 4 and 12 months.
Carlson et al (1999) Randomisation into control and LCPUFA formula groups
Randomisation, intervention and assessment were blinded.
0-12 months Assessment of weight, height and head circumference at 4 and 12 months.
Visual acuity and the Bayley Scales of Infant Development were assessed, however the data was not reported.
Randomisation into control and LCPUFA formula groups
Randomisation and intervention were blinded.
0-4 months Assessment of weight, height and head circumference at 4 months.
Randomisation into control and LCPUFA formula groups
Randomisation, intervention and assessment were blinded.
0-4 months Assessment of weight, height and head circumference at 4 months.
Groupings Infant Dietary Regime Details*
Infant Dietary Regime n Omega 6 LCPUFA (% wt)
Randomisation into control and LCPUFA formula groups
Randomisation, intervention and assessment were blinded.
0-4 months Assessment of visual acuity at 4 months.
Randomisation into control and LCPUFA formula groups
Randomisation, intervention and assessment were blinded.
0-4 months Assessment of weight, height and head circumference at 4 months.
Lucas et al (1999) Randomisation into control and LCPUFA formula groups
Randomisation, intervention and assessment were blinded.
0-18 months Assessment of weight, height and head circumference at 4, 6 and
Assessment of Bayley Scales of Infant Development at 18 months.
Infant Dietary Regime n Omega 6 LCPUFA (% wt)
Randomisation into control and LCPUFA formula groups
Randomisation, intervention and assessment were blinded.
0-12 months Assessment of weight, height and head circumference at 4 and 12 months.
Assessment of visual acuity at 4 and 12 months.
Randomisation into control and LCPUFA formula groups
Randomisation, intervention and assessment were blinded.
Assessment of weight, height and head circumference at 4, 8 and
Assessment of visual acuity at 4 and 8 months (Makrides et al., 2000c).
Assessment of Bayley Scales of Infant Development at 12 and
Morris et al (2000) Randomisation into control and LCPUFA formula groups
Randomisation, intervention and assessment were blinded.
0-12 months Assessment of weight, height and head circumference at 6 and 12 months.
Groupings Infant Dietary Regime Details*
Infant Dietary Regime n Omega 6 LCPUFA (% wt)
Randomisation into control and LCPUFA formula groups
Randomisation and assessment were blinded.
Assessment of cognitive performance using a means-end problem solving test.
Several studies involving a Human Milk group did not analyze breast milk samples for fatty acid content, indicating this data as 'n/a' Instead, researchers utilized previously gathered information on human milk composition that was pertinent to their specific population group.
Table A2: Anthropometric results from studies on the LCPUFA content of infant formulas (0-12 months of age)
Study Subject groups Anthropometric Results (mean + sd) 1
Weight (kg) Length (cm) Head Circumference (cm)
The data presents a formula for standard deviations (sd) at various developmental stages: at birth, 4 months, 6 months, 8 months, and 12 months Each time point is crucial for understanding growth patterns and developmental milestones Monitoring these standard deviations helps in assessing the overall health and progress of infants during their early months.
Agostoni et al.(1994) Human Milk 15 3.37 0.49 6.45 0.79 50.4 1.7 63.1 2.6 34.3 1.5 41.8 0.9
Auestad et al (1997) Human Milk 63 3.6 0.46 6.85 0.80 9.95 1.21 50.8 3.1 62.8 2.3 75.3 2.8 34.8 1.5 41.8 1.1 46.6 1.2
Standard formula 45 3.6 0.47 6.97 0.66 10.23 1.18 50.9 2.9 62.9 2.2 75.4 3 34.8 1.5 41.9 1.1 46.7 1.3 Standard + DHA 43 3.57 0.46 6.76 0.88 10.16 1.22 51 2.3 62.8 2.2 75.3 2.6 34.9 1.7 41.6 1.1 46.5 1.2 Std + DHA + AA 46 3.5 0.46 6.79 0.82 10.06 1.26 50.6 2.7 62.9 2.4 75.5 2.6 34.5 1.5 41.8 1.1 46.7 1.2
Auestad et al (2001) Standard formula 77 3.45 0.44 6.54 0.64 9.78 1 50.8 2.5 63 2.2 75.4 2.7 39.4 1.2 41.8 1.1 46.5 1.2
Carlson et al (1996) Standard formula 20 3.33 0.33 6.4 0.72 9.48 1 61.3 2.1 72.5 2.3 41.5 0.8 46.3 1.4
Carlson et al (1999) Standard formula 104 6.63 0.74 9.77 1.19 63 2.6 75.4 3 41.7 1.2 46.8 1.4
Study Subject groups Anthropometric Results (mean + sd) 1
Weight (kg) Length (cm) Head Circumference (cm)
The article presents a formula that outlines the standard deviations (sd) for various age milestones, including birth, 4 months, 6 months, 8 months, and 12 months It emphasizes the significance of tracking these developmental benchmarks to ensure healthy growth and development in infants Understanding these standard deviations is crucial for parents and healthcare providers to monitor progress and identify any potential concerns early on.
Lapillonne et al (2000) Human Milk 13 3.47 0.41 6.6 0.64 50.3 1.4 62.9 1.7 34.8 1.1 41.2 1.1
Makrides et al (1995a) Standard formula 19 36.5 0.42 6.7 0.79 9.98 1.09 51.2 2.1 62.7 1.5 75.8 2.2 35.2 1.2 42.2 0.9 46.9 1.1
Makrides et al (1999) Standard formula 22 3.55 0.5 6.5 0.53 8.78 0.9 10.62 1.13 51.5 2.6 62.6 2.5 71 2.4 77 2.4 35.3 1.6 41.5 1.1 44.9 1.2 46.9 1.2
Standard + DHA 25 3.38 0.43 6.53 0.65 8.62 0.99 9.96 1.11 50.8 2 62.2 1.6 70.3 2 75.5 2.3 35.1 1.4 41.8 0.9 44.9 1.2 46.8 1.1 Std + DHA + AA 24 3.55 0.52 6.65 0.73 8.99 0.99 10.55 1.11 51.3 2.4 62.6 2.5 71 2.4 77 2.4 35.2 1.7 42 1.5 45.6 1.4 47.6 1.5 Morris et al
1 Bolded values with different lettered superscripts are significantly different from each other (p0.05) Statistical significance is only applied to comparisons between infants fed different study formulas, and not to comparisons with infants fed human milk.
Table A3: Visual acuity results from studies on the LCPUFA content of infant formulas (4-12 months of age)
Study Subject groups Visual Acuity Results (mean + sd) 1
Behavioural Assessment (LogMAR) 2 Visual Evoked Potential Assessment (LogMAR) 2 Stereoacuity Assessment
Type Formula n 4 mths sd 6 mths sd 12 mths sd 4 mths sd 6 mths sd 8 mths sd 12 mths sd 4 mths sd 10 mths sd 12 mths sd
Study Subject groups Visual Acuity Results (mean + sd) 1
Behavioural Assessment (LogMAR) 2 Visual Evoked Potential Assessment (LogMAR) 2 Stereoacuity Assessment
Type Formula n 4 mths sd 6 mths sd 12 mths sd 4 mths sd 6 mths sd 8 mths sd 12 mths sd 4 mths sd 10 mths sd 12 mths sd
1 Bolded values with different lettered superscripts are significantly different from each other (p