Download Health effects of resistant starch

REVIEW
DOI: 10.1111/nbu.12244
Health effects of resistant starch
S. Lockyer* and A. P. Nugent†
*British Nutrition Foundation, London, UK;
†
University College Dublin, Dublin, Ireland
Abstract
The merits of a fibre-rich diet are well documented. Resistant starch (RS) is a
form of starch that resists digestion in the small intestine and, as such, is
classified as a type of dietary fibre. RS can be categorised as one of five types
(RS1–5), some of which occur naturally in foods such as bananas, potatoes,
grains and legumes and some of which are produced or modified commercially,
and incorporated into food products. This review describes human evidence on
the health effects of RS consumption, with the aim of identifying any benefits of
RS-rich foods and RS as a functional ingredient. The reduced glycaemic response
consistently reported with RS consumption, when compared with digestible
carbohydrate, has resulted in an approved European Union health claim. Thus,
RS-rich foods may be particularly useful for managing diabetes. There appears to
be little impact of RS on other metabolic markers, such as blood pressure and
plasma lipids, though data are comparatively limited. Promising results on
markers of gut health suggest that further research may lead to the classification
of RS as a prebiotic. Microbial fermentation of RS in the large intestine to
produce short-chain fatty acids likely underpins some of its biological effects,
including increasing satiety. However, effects on appetite have not resulted in
notable changes in bodyweight after long-term consumption. Emerging research
suggests potential for RS as an ingredient in oral rehydration solutions and in the
treatment of chronic kidney disease. Overall, RS possesses positive properties as
a healthy food component.
Keywords: amylose, fibre, glycaemia, resistant starch, satiety, short-chain fatty acids
Introduction
The importance of dietary fibre has been recognised
by health authorities globally for many years (IOM
2002; Mann et al. 2007; EFSA Panel on Dietetic Products Nutrition and Allergies 2010a). As such, recommendations for fibre intakes feature in national and
international dietary guidelines. However, the details
of the recommendations differ between nations
Correspondence: Dr. Stacey Lockyer, Nutrition Scientist, British
Nutrition Foundation, Imperial House, 15-19 Kingsway, London
WC2B 6UN, UK.
E-mail: [email protected]
© 2016 British Nutrition Foundation
(Lockyer et al. 2016). A recent review linked higher
fibre intakes with a reduction in the risk of developing
type 2 diabetes, cardiovascular disease (CVD) and colorectal cancer (SACN 2015). Biological effects consistently demonstrated in randomised controlled trials
(RCTs) include decreased transit time and increased
faecal bulk (SACN 2015).
Dietary fibre is almost universally defined as the
material isolated by methods approved by the Association of Official Analytical Chemists (AOAC). Older
AOAC methods measured non-starch polysaccharides
(NSP), lignin, some inulin and some resistant starches
and non-digestible oligosaccharides, but not all
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S. Lockyer and A. P. Nugent
(Prosky et al. 1988; Lee et al. 1992). The current
AOAC method (2009.01) measures all carbohydrates
that are neither digested nor absorbed in the small
intestine and have a degree of polymerisation of three
monomeric units or more (i.e. NSP, non-digestible
oligosaccharides, all resistant starches and polydextrose, plus lignin; McCleary et al. 2012). Until
recently in the UK, dietary fibre was defined as NSP
[measured using the Englyst method (Englyst et al.
1994)] and dietary intakes were reported in this way
but food labels list AOAC values in alignment with
European Union (EU) law (European Commission
2011). In 2015, the UK Scientific Advisory Committee
on Nutrition (SACN) recommended that the AOAC
definition should now be used for all purposes (SACN
2015) and revised (higher) reference values were set,
reflecting the strengthening of evidence since recommendations were last made in 1991. These include reference intakes for children of different ages.
Resistant starch (RS) is a fraction of starch that
resists digestion within the small intestine, reaching
the large intestine intact. RS is then fermented by
microbes in the large intestine, producing short-chain
fatty acids (SCFAs). The term ‘resistant starch’ was
coined by Englyst and colleagues in the 1980s (Englyst
et al. 1982). An array of health benefits have been
attributed to RS, and this paper serves as an update to
our 2005 review of this topic (Nugent 2005). The
main areas covered are gut health, glycaemia and
plasma lipid effects, satiety and bodyweight. Prominent human studies published in English from January
2005 to July 2016 have been considered.
Starch types
Starch is a compound present in plants for the storage
of glucose and is made up of two polymers: amylose,
which is a linear molecule, and amylopectin, which is
branched. Distinct crystalline forms of amylose and
amylopectin have been identified in starch granules.
Type A is characteristic of cereals, type B is more
commonly present in potatoes and bananas, and type
C is an intermediate form found in legumes. Starch is
digested by a-amylase in the mouth, pancreatic amylase, and glucoamylase and sucrose-isomaltase embedded in the membrane of microvilli within the small
intestine. The resultant glucose is then absorbed.
Starch can be classified into rapidly digestible, slowly
digestible and RS. RS resists hydrolysis by the digestive enzymes a-amylase and pullulanase in vitro
beyond 120 minutes, unlike both rapidly digestible
and slowly digestible starch (Englyst et al. 1982).
Classification of resistant starches and factors
affecting resistance to digestion
There are five types of RS.
• RS1 – inaccessible to digestive enzymes due to the
physical barriers formed by cell walls and protein
matrices. Less resistant to digestion compared with
other types.
• RS2 – starches protected from digestion due to their
crystalline structure.
• RS3 – retrograded starch formed when starchy
foods (e.g. potatoes, pasta) are cooked then cooled.
Long-branched chains of amylopectin form double
helices that cannot be hydrolysed by digestive
enzymes.
• RS4 – chemically modified starch formed by crosslinking, etherisation or esterification.
• RS5 – two different components have been proposed as RS5. The first comprises amylose–lipid complexes, which either form during processing and
reform after cooking or can be created artificially and
added to foods (Seneviratne & Biliaderis 1991; Hasjim
et al. 2010, 2013; Lau et al. 2016). The second is
resistant maltodextrin, which is processed to purposefully rearrange starch molecules (Mermelstein 2009).
The majority of publications describe RS5 as amylose–
lipid complexes.
Amylose is digested slowly, whereas amylopectin is
digested rapidly. Therefore, in general, the RS content of starch is positively associated with the
amount of amylose present. Other factors that affect
the resistance of starch include the size and type of
starch granules; the physical form of grains and
seeds; plant genotype and mutations [genetic engineering can be used to increase RS content (Wei
et al. 2010; Carciofi et al. 2012)]; crop-growing location; associations between starch and other food
components [i.e. lipids, proteins, sugars, gums, other
fibre types and plant bioactives that inhibit a-amylase
(Lochocka et al. 2015)]; and food processing methods
such as milling, cooking, annealing (physical modification of starch in water at temperatures below gelatinisation), high-pressure processing, autoclaving, cirradiation, extrusion and storage time (Seneviratne
& Biliaderis 1991; Englyst et al. 1992; Muir &
O’dea 1992; Chung et al. 2009; Chung & Liu 2010;
Rohlfing et al. 2010; Singh et al. 2010; Pollak et al.
2011; Linsberger-Martin et al. 2012; Dundar & Gocmen 2013). Grinding of grains during processing can
reduce RS1, due to the breakdown of cell walls, and
cooking starchy foods in water can lead to gelatinisation, which reduces resistance to digestion. In
© 2016 British Nutrition Foundation
Health effects of resistant starch
contrast, cooking and cooling before eating (e.g. new
potatoes for potato salad) can produce RS3. A recent
study reported that cooked then chilled potatoes contained more RS than either hot or reheated potatoes.
In addition, baked potatoes had higher RS contents
than boiled and there was no impact of potato variety on RS (Raatz et al. 2016). However, a further
study found that there were significant differences in
RS content between potato varieties (Pinhero et al.
2016).
Food sources of resistant starch and dietary intake
Table 1 details the different types of RS and Table 2
provides estimates of the total RS content of a variety
of common foods, although it is important to reiterate
that values will vary considerably due to factors such
as cooking and storage. The best natural sources may
include less ripe bananas, pasta, pulses and potatoes.
It is of note that wholegrain versions of starchy foods
(e.g. wholewheat pasta, brown rice) contain more RS
than refined versions. In the 1990s, Baghurst and colleagues suggested that 20 g of RS per day is needed to
confer benefits related to gut health (Baghurst et al.
1996); however, there are no official intake recommendations for RS. At present, dietary intakes of RS
are not routinely reported and RS is not typically
included in food composition databases or national
dietary surveys (e.g. the National Diet and Nutrition
Survey) as a discrete entity. Accurate assessment of
dietary intake is difficult due to factors that affect concentration in foods such as ripening, natural variation,
losses, which occur during cooking and storage, and
potential gains due to the formation of RS3 after
cooking and cooling. These factors, plus others listed
in the previous section and differences related to the
measurement of RS (see ‘Methods of analysis of
Table 1 Food sources of resistant starch (RS) types
RS1
RS2
RS3
RS4
RS5
Coarsely ground or whole kernel grain products (e.g. bread, seeds
and legumes)
Raw potatoes, green bananas, high-amylose maize, ginkgo starch
Cooked, then cooled starchy foods such as potatoes, bread
(especially stale bread), pasta, rice, cornflakes
Foods containing chemically modified starches, such as cross-linked
starch and octenyl succinate starch (e.g. some commercially
produced breads and cakes)
Foods containing naturally occurring amylose–lipid complexes, such
as bread containing fat as an ingredient, or foods containing
artificially made amylose–lipid complexes, such as stearic
acid-complexed high-amylose starch
© 2016 British Nutrition Foundation
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Table 2 Typical amounts (g) of resistant starch present in selected
foods relevant to the UK diet
White bread rolls
Wholemeal bread rolls
Mixed grain bread rolls
Porridge (cooked)
Breakfast cereal, wheat biscuits
Bran breakfast cereal
White rice (long grain, cooked)†
Brown rice (cooked)†
Egg pasta
Wheat pasta (white, cooked)
Wholewheat pasta (cooked)
Bananas (ripe)
Bananas (green)
Sweet potato
Green beans
Sweetcorn (canned)†
Peas
Hummus
Baked beans
Kidney beans†
Chickpeas
Lentils (cooked)†
Potato crisps†
Hot potatoes (e.g. boiled,
mashed, baked chips)
Cold potato dishes
(e.g. potato salad)
Potato products [e.g. hash browns,
wedges (cooked)]
Per 100 g
(range)
Per
serving*
0.87
0.87
0.97
0.17
1.12
1.22
1.2 (0–3.7)
1.7 (0–3.7)
0.88
1.1
1.4
1.23
8.50
0.08
0.14
0.30
0.77
0.66
1.40
2.0 (1.5–2.6)
2.08
3.4 (1.6–9.1)
0.21 (2.9–4.5)
0.59
0.44
0.42
0.54
0.27
0.45
0.49
2.16
3.06
2.02
2.53
3.22
0.98
6.80
0.06
0.11
0.24
0.62
0.33
1.12
1.60
1.66
2.72
0.07
1.03
0.63
0.54
1.07
0.62
Values provided represent total RS, individual RS types not stated. Ranges
given were reported. Items with no superscript, values derived from Landon
et al. (2012).
†
Values derived from Murphy et al. (2008).
*Serving sizes as per Food Portion Sizes (FSA 2006) or 80 g for fruit, vegetables and pulses.
resistant starch in foods’ section), mean that quantities
present in identical food types can vary.
Estimates indicate that intakes are low in developed
countries. For example, in the 1990s in the UK, average RS intake was estimated to be 3 g per day, an
analysis published in 2008 estimated average intakes
in the US to be 5 g per day (Murphy et al. 2008) and
a recent study in Serbia calculated average intakes to
be around 6 g per day, with RS contributing 30% of
total dietary fibre (Dodevska et al. 2016). In developing countries, intakes may be up to 30–40 g per day
due to differences in dietary composition (Baghurst
et al. 2001).
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S. Lockyer and A. P. Nugent
In 2013, the United Nations declared 2016 to be
the ‘Year of the Pulses’ in order to raise awareness of
and position pulses as a primary source of protein and
other essential nutrients, with messaging focusing on
the nutritional composition and health benefits (FAO
2016). If successful, this initiative may increase consumption of pulses and therefore RS.
Methods of analysis of resistant starch in foods
A variety of methods exist to measure either total RS
or specific types of RS in vitro, aiming to mimic
human physiological conditions by first grinding
samples (as would occur with mastication) or even
self-chewing (
Akerberg et al. 1998), removing hydrolysable starch with enzymes and incubating at body
temperature (as during digestion). These processes
have been described in detail elsewhere (Perera et al.
2010). The Megazyme RS assay kit (Megazyme 2015),
based on the American Association of Cereal Chemists
Method (AACC 32-40; American Association of
Cereal Chemists 2000) and AOAC 2002.02 method
(McCleary & Monaghan 2002), is widely used at
present.
Different methods yield different quantitative results
due to varying sample preparation, enzymes used and
length of incubation periods. For example, the RS
content of cornflakes has been reported as 2.2% when
using the Megazyme assay (McCleary et al. 2002) and
3% and 6.5% using two other methods (Englyst et al.
1992; Muir & O’dea 1992). There is evidence that the
amount of RS available in the colon after food consumption varies from person to person due to individual difference in chewing habits (Englyst et al. 1992).
RS can also be determined in vivo in studies of
patients with ileostomies (McCleary 2013).
Challenges in developing food products with added
resistant starches
As mentioned above, cooking and preparation of food
products can greatly affect the RS content. For example, extrusion cooking followed by cooling has been
reported to increase RS3 formation in some studies,
but decrease RS3 formation in others (Rabe & Sievert
1992; Adamu 2001); therefore, manipulating RS naturally present within foods can be complex. Manufactured purified forms of RS are commercially available
and have been listed elsewhere (Fuentes-Zaragoza
et al. 2011; Raigond et al. 2015). However, some
types of RS are not suitable as ingredients in certain
food products because they may be destroyed by the
food processing methods (e.g. high temperatures in the
case of RS1 and RS2).
In general, RS has good potential as a functional
ingredient due to its fine particle size, pale colour,
bland flavour, good extrusion and film-forming
properties, high gelatinisation temperature, low
calorific value (1.6–2.8 kcal/g) and low water binding capacity, which can improve shelf-life of dry
products and prevent the formation of ice crystals in
ice cream (Elia & Cummings 2007; Tulley et al.
2009; Raigond et al. 2015). Such properties have led
to RS being successfully incorporated into a variety
a foods, such as dairy products, baked goods and
pasta (Noronha et al. 2007; Almeida et al. 2013;
Aravind et al. 2013). The first of these products was
introduced commercially in Australia in the mid1990s (Roberts et al. 2004). RS has also been used
in the microencapsulation both of probiotics in dairy
products (Vandamme et al. 2016), in an attempt to
increase viability, and of fish oil to reduce odour
and oxidation (Nasrin & Anal 2015).
Nevertheless, the inclusion of ingredients within
products to increase the RS content requires careful
consideration because of the potential impact on
functional and rheological properties. For example,
adding RS3 to batter can increase the crispiness and
golden colour of the product (Sanz et al. 2008), but
adding green banana flour to instant noodles can
produce a weaker dough and less firm noodles due
to the dilution of gluten, although less oil may be
needed for frying (Vernaza et al. 2011). In addition,
bread loaf volume has been reported to decrease
with the addition of high levels of RS2 and RS3
(Ozturk et al. 2009) and when high-amylose wheat
flour is used in bread making (Van Hung et al.
2005). Furthermore, RS2 and RS3 added to muffins
has been found to have a negative impact on texture,
making them more dense and less springy (Sanz
et al. 2009).
Safety
Under EU Regulation 1333/2008, native starches and
starch modified by acid or alkali treatment, bleached
starch, physically modified starch and starch treated
by amylolytic enzymes are considered to be normal
ingredients rather than food additives (European Parliament 2008). After assessment by the European
Food Safety Authority (EFSA) as part of a novel food
application (EFSA Panel on Dietetic Products Nutrition and Allergies 2010b), one type of chemically
modified starch, phosphated distarch phosphate
© 2016 British Nutrition Foundation
Health effects of resistant starch
(RS4), was deemed safe and unlikely to be allergenic
in adults and children, at a maximum level of 15%,
when added to low-moisture food products (such as
baked goods, pasta, snacks and breakfast cereals). An
unpublished study submitted as part of the application reported no adverse effects in ten volunteers consuming 60 g of potato starch or five chemically
modified starches, including phosphated distarch
phosphate on 4 days per week for 6 weeks. Other
studies testing both lower and higher doses of RS (up
to 100 g/day) have reported increased gastrointestinal
symptoms, such as diarrhoea in some subjects
(Grabitske & Slavin 2009), but such high doses are
far in excess of what would normally be (and could
easily be) consumed by the general population. In
February 2016, EFSA called for submission of technical data relating to certain starches and celluloses,
including types of RS4 such as hydroxypropyl distarch phosphate (E1442) and acetylated distarch adipate (E1422), so that the safety of these additives can
be reassessed (EFSA Food Ingredients and Packaging
Unit 2016).
Labelling and health claims
RS meets the EU definition of fibre specified by Commission Directive 2008/100/EC (European Commission 2008), which refers to a statement produced by
EFSA’s Panel on Dietetic Products Nutrition and
Allergies (2007). As such, the energy value of RS
from a labelling perspective is 2 kcal/g (European
Commission 2011). Material constituting dietary fibre
is defined as carbohydrate polymers with three or
more monomeric units, which are neither digested
nor absorbed in the human small intestine, and is
either naturally occurring in food; obtained from food
raw material by physical, enzymatic or chemical
means (and with a beneficial physiological effect
demonstrated by generally accepted scientific evidence) or edible synthetic carbohydrate polymers
(that have a beneficial physiological effect demonstrated by generally accepted scientific evidence)
(European Commission 2011). Declaring the quantity
of fibre present in a food is not a mandatory component of nutrition information on food labels, but
can be stated voluntarily in the format set out
within the EU Food Information for Consumers
Regulations (European Commission 2011). However,
fibre values are not permitted on front-of-pack nutrition labels. Manufacturers can voluntarily claim
foods as a ‘source of fibre’ if it contains at least 3 g
of fibre per 100 g or 1.5 g of fibre per 100 kcal, or
© 2016 British Nutrition Foundation
5
‘high in fibre’ if it contains at least 6 g per 100 g
or 3 g per 100 kcal. Where these claims are used,
the fibre content must be listed in the nutrition
information on the back-of-pack (European Commission 2006).
A relevant health claim has been approved by
EFSA with the wording ‘Replacing digestible starch
with resistant starch induces a lower blood glucose
rise after a meal’ (EFSA Panel on Dietetic Products
Nutrition and Allergies 2011b). This health claim can
be applied to RS from all sources used to replace
digestible starch in high carbohydrate-baked foods (at
least 14% of the total starch content must be RS).
Health claim applications relating to RS and digestive
health have not been authorised, as the biological
effects in the submitted dossiers were deemed to be
general, non-specific and not in reference to any
specific health claims (EFSA Panel on Dietetic Products Nutrition and Allergies 2011b). According to
EFSA guidance, physiological effects considered to be
beneficial for the general population with regard to
gastrointestinal (GI) health include reducing GI discomfort, which is considered an indicator of
improved GI function, and the maintenance of normal defecation, defined as increasing the frequency of
bowel movements and faecal bulk, and loosening the
consistency of stools (e.g. as indicated by the Bristol
Stool Form Scale) and decreasing transit time. Evidence for sustained health benefits with continuous
consumption of the food/constituent over extended
periods of time (e.g. 4–8 weeks) should be provided
(EFSA Panel on Dietetic Products Nutrition and
Allergies 2016). Claims relating to the maintenance
of normal defecation have been evaluated with a
favourable opinion for other fibre types, such as
wheat bran (EFSA Panel on Dietetic Products Nutrition and Allergies 2010d), rye (EFSA Panel on Dietetic Products Nutrition and Allergies 2011d), oat and
barley grain fibre (EFSA Panel on Dietetic Products
Nutrition and Allergies 2011c) and the prebiotic inulin from chicory (EFSA Panel on Dietetic Products
Nutrition and Allergies 2015). Unfavourable opinions
were given to health claim applications relating to
resistant maltodextrins and a reduction in postprandial glycaemic responses, maintenance of normal
blood LDL-cholesterol concentrations, maintenance of
normal (fasting) blood concentrations of triglycerides
and changes in bowel function. This was because
most of the references provided in the applications
were unavailable in an EU language and, as such,
causality could not be established (EFSA Panel on
Dietetic Products Nutrition and Allergies 2011a).
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S. Lockyer and A. P. Nugent
Key points
• RS is a type of dietary fibre. It passes through the
small intestine intact and is then fermented in the
large intestine, producing SCFAs.
• RS provides ~2 kcal/g.
• There are five different types of RS (RS1, RS2, RS3,
RS4 and RS5).
• RS is present in grain products, seeds, pulses, bananas, potatoes and in commercially purified forms,
which can be added to food products.
• RS intake is estimated to be around 3 g/day in the
UK and is likely to be similar in other countries with
Western-style diets.
Resistant starch and colonic health
As a fibre type, RS would be expected to confer benefits to gut health, particularly in the large intestine
where RS is fermented and can result in the release of
gases (methane, hydrogen, carbon dioxide), SCFAs
(formate, acetate, propionate, butyrate and valerate)
and smaller amounts of organic acids (lactate and succinate) and alcohols (methanol and ethanol).
Described in detail elsewhere (Birt et al. 2013), this
process involves several key bacterial groups, such as
amylolytic gut bacteria (including Firmicutes, Bacteroidetes and Actinobacteria), which mediates starch
(amylose) breakdown; butyrogenic archaea (including
Eubacterium rectale), which is involved in butyrate
production; and methanogenic archaea, which is necessary to produce methane. In general, studies that
have investigated the influence of RS on gut health
have focused on endpoints such as gas production,
SCFAs and gut bacterial composition. Although less is
known about the influence of RS on other breakdown
products, the SCFA butyrate is of particular interest
given its role as fuel for the cells lining the colon
(colonocytes) and there is growing interest in the
potential influence of gut bacteria on health outcomes,
both locally in the gut and systemically (Kataoka
2016). The following section will examine the influence of RS on important markers of gut health and
the gut microbiome.
Short-chain fatty acid production
As mentioned, the SCFA butyrate is the preferred fuel
for colonocytes, increasing colonic blood flow, lowering luminal pH and helping prevent the development
of abnormal colonic cell populations (Topping &
Clifton 2001). The concentrations of all SCFAs are
typically higher in the proximal colon where fermentation is greatest and the amount present relates to the
supply of carbohydrates in the diet (Topping et al.
2003). In humans, SCFA abundance is typically
acetate > propionate > butyrate (Schwiertz & Lehmann 2002). Dietary interventions that increase the
amount of SCFAs, particularly butyrate, in the colon
are thought to be beneficial to gut health, with such
SCFA levels commonly used as a marker of fermentation and colonic health. However, faecal SCFAs are
poor markers of colonic production as it is estimated
that approximately 95% of SCFAs produced are
absorbed by the colon (Cummings et al. 1987). Furthermore, faecal SCFAs may not be wholly reflective
of fermentation at the luminal surface and may exhibit
significant inter-individual variation (McOrist et al.
2011). Isotopic dilution has been suggested as the
gold standard (Sakata et al. 2003). EFSA’s NDA
Panel does not consider changes in SCFA production
in the gastrointestinal tract to be a beneficial physiological effect per se, and states that any changes would
need to be linked to a beneficial physiological or clinical outcome (EFSA Panel on Dietetic Products Nutrition and Allergies 2011e, 2011f).
Earlier studies describe the ability of RS to modulate SCFA production in vitro and in animal and
human feeding studies; this research has been reviewed
elsewhere (Nugent 2005; Birt et al. 2013). While a
number of human studies found increased faecal
excretion of SCFA (concentrations and molar ratio),
specifically butyrate, following supplementation with
RS (Young & Le Leu 2004; Nugent 2005; Birt et al.
2013), not all studies conclusively show that all types
of RS increase SCFA production in an equal manner.
This is perhaps due to differences in study design and/
or control vehicle and given that SCFAs are both produced and absorbed by the colon (Cummings et al.
1987; see Table S1). For example, human colonic
microbiota cultured with a laboratory generated RS3
increased butyric acid production (Lesmes et al.
2008). However, in interventions with healthy young
adults, there were no changes in total faecal SCFA
production following supplementation with RS3, in
the form of a heat- and moisture-treated high-amylose
maize starch (HAMS), at 12 g/day for 14 days (Stewart
et al. 2010) or 20 g/day for 7 days (Klosterbuer et al.
2013), albeit that faecal propionate decreased by 8%
(P < 0.05) in one study (Stewart et al. 2010) with a tendency (P > 0.05) for an increase in the proportion of
butyrate. In another example, in middle-aged adults
selected to have lower-than-average faecal butyrate
concentrations, no change in faecal SCFA
© 2016 British Nutrition Foundation
Health effects of resistant starch
concentrations was found following supplementation
with RS2 (HAMS; 20 or 40 g/day for 14 days) (Clarke
et al. 2011). In contrast, faecal SCFAs (acetate, propionate, butyrate and succinate) decreased relative to an
NSP-rich diet or control diet following RS3 supplementation (26 g/day for 3 weeks) in 14 overweight males
(Salonen et al. 2014).
Esterified or acylated forms of RS (e.g. acetylated,
butyrylated or propionylated RS4) offer specificity in
SCFA delivery. This is because specific SCFA are esterified to a carrier starch and released only in the large
intestine leaving the residual starch available for fermentation (West et al. 2013). Some initial studies have
looked at the effects of butylated forms of HAMS or
acetylated, propionylated or butyrylated HAMS in
healthy adults and humans with ileostomies. In general, these studies report increases in free faecal butyrate (Clarke et al. 2007), free, bound and total
butyrate and propionate (West et al. 2013) or delivery
to the ileostomy site (Clarke et al. 2011). However,
the lack of appropriate control groups (Clarke et al.
2011) and small sample sizes necessitate further study
in well-designed, randomised controlled trials.
The ability of naturally occurring RS to alter SCFA
production is also of interest, with recent work chiefly
focusing on barley that contains RS in addition to
other fibre types (e.g. NSP). A number of studies from
a Swedish research group took measurements in the
morning following an evening meal of barley kernel
bread, naturally rich in RS, or a white wheat flour
bread control. This study design allowed adequate time
for fermentation and study of ‘second meal effects’.
Significant increases in fasting breath hydrogen (an
indirect measure of colonic fermentation) of
140–160% (Nilsson et al. 2008, 2015; Sandberg et al.
2016), serum total SCFAs and acetate (both by 18%;
Nilsson et al. 2015) and total plasma SCFAs, acetate
and butyrate by 10–30% (Nilsson et al. 2010; Sandberg et al. 2016) were reported. Other work involving
barley has focused on a novel high-amylose barley
variety (Himalaya 292) rich in RS due to the absence
of activity of a key enzyme in starch synthesis, starch
synthase IIa. For example, a study was carried out in
middle-aged overweight volunteers who consumed
103 g of foods rich in the Himalaya 292 grain or a
wholegrain wheat cereal or refined cereal for four
weeks; though exact amounts of RS consumed were
not defined (Bird et al. 2008). Ninety-one per cent
higher faecal excretion of butyrate and 57% higher
faecal total SCFA excretion were reported compared
with the refined cereal control (Bird et al. 2008). In a
further study using Himalaya 292, the influence of RS
© 2016 British Nutrition Foundation
7
from a combination of sources on faecal butyrate concentrations and excretion was examined (McOrist
et al. 2011). For 4 weeks, 46 healthy adults consumed
either 25 g of NSP or 25 g of NSP plus 22 g of RS
from a mix of sources [Himalaya 292, canned legumes
and HAMS (RS2; HI-MAIZEâ 260 Resistant Starch1)].
Overall, acetate, butyrate and total SCFA concentrations were significantly higher in the RS group, compared with baseline levels and control (NSP only
group). However, there was a large degree of interindividual variation in responses, with differences in
concentration and excretion also noted by gender
(McOrist et al. 2011).
It is perhaps unsurprising that effects of RS on
SCFA production reported in vitro and in animal
models are not replicated easily in human studies.
Type and dose of RS, esterification and the food form
in which RS is incorporated should be considered,
given that RS is not a homogenous group. Recent
in vitro experiments, examining the fermentation of
RS3 from different plant sources by different bacteria,
reported very different SCFA concentrations (Purwani
et al. 2012). As mentioned, the majority of SCFAs
produced are absorbed by the colon, with mechanisms
thought to include non-ionic diffusion and transporter-mediated mechanisms coupled with sodium
(Cummings et al. 1987; Scheppach 1994; Binder
2010). Hence, such effective utilisation by colonocytes
may not allow for the detection of (subtle) differences
in SCFA production between treatments (Anson et al.
2011). Furthermore, it has been suggested that faecal
SCFAs (the main outcome measure of many studies)
may only reflect production of SCFAs in the distal
colon. Hence, positive outcomes may be more likely
to arise with RS forms with more delayed fermentation rates (e.g. RS4; Upadhyaya et al. 2016) or those
present in combination with other more slowly fermentable fibres (e.g. wheat bran; James et al. 2015).
Factors affecting faecal SCFA concentrations other
than site of digestion include transit rate and the moisture content of the digesta (Salonen et al. 2014).
Other measures of SCFA production include peripheral blood (plasma/serum) concentrations and/or
breath hydrogen. However, both are indirect measures
and may lack sensitivity to detect treatment differences. In acute feeding studies, timing of measurements should also be considered. For example, in one
study using isotopic dilution, increases in 13C-acetate
were only observed <6 hours and increases in 13C1
The HI-MAIZE, NOVELOSE and INGREDION marks and logo
are trademarks of the Ingredion group of companies.
8
S. Lockyer and A. P. Nugent
propionate and 13C-butyrate only observed >6 hours
post-consumption of labelled intact barley kernels
(rich in RS and NSP; Verbeke et al. 2010).
There appears to be large inter-individual variability
in butyrate production and responsiveness to RS interventions, likely influenced by differences in microbiota
composition between individuals. Such variability may
be difficult to capture when using small sample sizes,
short study durations (Cummings et al. 1996) or smaller doses of RS (<20 g/day; Topping & Clifton 2001).
In one of the largest studies published to date [n = 46
with 25 g/day RS delivered via various foods (cereal,
legumes, commercial RS preparations) for 4 weeks],
approximately 10% variability in baseline total and
individual SCFA production was noted, with body
mass index (BMI) explaining 27% of variation in
butyrate production (McOrist et al. 2011). Furthermore, differences in response were observed by gender
and the greatest responses to RS supplementation were
observed for individuals with the lowest habitual
intakes. The greatest decrease in butyrate production
was noted when baseline levels were high. Future
studies should factor such considerations into their
design.
Influence of resistant starch on gut bacteria and the
microbiome
The influence of gut bacteria and the microbiota on
human health is well recognised. Gut bacteria may
influence immune function and nutritional acquisition
(Sekirov et al. 2010); appetite control mechanisms [as
demonstrated in mice (Lyte et al. 2016)]; disease states
such as mental health disorders (Flowers & Ellingrod
2015) and obesity and its associated metabolic
imbalances, including CVD (Arora & Backhed 2016;
Kobyliak et al. 2016). Diet is believed to influence the
microbial communities of the gastrointestinal tract
(Birt et al. 2013) and so the potential of RS to influence gut bacteria is of interest.
Prior to advances in DNA sequencing, the influence
of RS on gut microbiota was inferred through its
effects on colonic pH, SCFA composition, reductions
in harmful metabolites (e.g. bile acids, phenols and
ammonia) and enzymatic activity associated with bacterial degradative pathways. Early human intervention
trials suggested reduced faecal ammonia, phenols, pH
and secondary bile acid concentrations in faecal water
with RS intake [for review, see Nugent (2005)]. More
recent human studies (post-2005, see Table S1) typically show no statistical differences in stool pH following supplementation with RS (Martinez et al.
2010; Stewart et al. 2010; Clarke et al. 2011; Klosterbuer et al. 2013), with only one study (using the
Himalaya 292 grain) reporting reduced stool pH (Bird
et al. 2008). However, reduced faecal p-cresol concentrations (an end-product of protein breakdown) of a
magnitude of 20–33% have been reported (Bird et al.
2008; Clarke et al. 2011), and higher ammonia concentrations, but not excretions, have been reported in
males only (McOrist et al. 2011).
Advances in sequencing platforms and culture-independent molecular methods, based on analysis of 16S
ribosomal RNA, have allowed more detailed investigations into how bacterial communities interact with the
different starch forms. For example, while one study
reported no change in faecal pH, changes in the faecal
microbial communities were described that were
dependent on RS type (Martinez et al. 2010). In a
double-blind crossover trial, ten healthy young adults
consumed crackers containing approximately 30 g of
RS2 (HI-MAIZEâ 260 Resistant Starch) or RS4
(FibersymTM) or control (4 g of fibre) for 3 weeks with
a 2-week wash-out period. During this short intervention, both forms of RS increased representatives of the
Actinobacteria and Bacteroidetes phyla and decreased
Firmicutes. However, while RS2 increased the abundance of Ruminococcus bromii (Firmicutes) and
E. rectale (Firmicutes), RS4 was associated with
increased Bifidobacterium adolescentis (Actinobacteria) and Parabacteroides distasonis (Bacteroidetes),
with the differential activities thought to reflect differences in substrate binding. Furthermore, there was a
significant inter-individual variation in response
among the ten volunteers (Martinez et al. 2010).
Ruminococcus bromii has also been implicated as
abundant in humans and significant in the fermentation of complex carbohydrates including RS2 (HIMAIZEâ 260 Resistant Starch; Abell et al. 2008),
while P. distasonis reportedly facilitates the release of
esterified butyrate from butyrylated HAMS (RS2;
Clarke et al. 2011; West et al. 2013). The influence of
approximately 25 g of RS3 or NSP (wheat bran) or a
weight-loss diet on colonic microbiota in overweight
men was studied (Walker et al. 2011). Using 16S ribosomal RNA gene sequencing, bacterial profiles were
found to be consistent over time within an individual
for a given diet, but to alter substantially between
diets. Although lacking a true control group,
R. bromii increased the most on the RS diet (17% of
total bacteria vs. 3.2% after the NSP diet), while
increases were also observed for the Oscillibacter
(Oscillibacter guillermondii) bacteria during the RS
diet and during the weight loss component.
© 2016 British Nutrition Foundation
Health effects of resistant starch
Eubacterium rectale increased on the RS diet to
approximately 10% of total bacteria. Subsequent indepth microarray analysis of this cohort revealed an
overall reduced total number and diversity of microbiota following the RS diet (Salonen et al. 2014). In
addition to confirming the changes in R. bromii and
Oscillibacter guillermondii, they also noted changes in
other lower abundance bacterial groups [e.g. increases
in Ruminococcaceae (Sporobacter termitidis, Clostridium leptum and C. cellulosi)], Bacteroidetes (Alistipes
spp.) and decreases in bacteria related to Papillibacter
cinnamivorans. Furthermore, while diet explained
10% of the total variance in microbiota composition,
as reported elsewhere (Martinez et al. 2010; McOrist
et al. 2011), individual SCFA response was highly
variable. In a follow-up in vitro study, R. bromii was
identified as a key species for RS breakdown in the
colon, facilitating RS fermentation by other species,
even bacteria that are weak RS2 and RS3 fermenters
in isolation (e.g. E. rectale and B. thetaiotaomicron;
Ze et al. 2012).
The influence of a wheat-derived RS4-enriched flour
or a control flour on gut bacteria and health outcomes
was recently studied in 20 individuals with metabolic
syndrome (Upadhyaya et al. 2016). The authors
reported increases in B. adolescentis, P. distasonis and
the newly described species, Christensenella minuta,
and no difference in R. bromii in response to
12 weeks’ consumption. The authors completed associational analysis, linking bacterial species with SCFA
production and with markers of metabolic health,
such as cholesterol, cytokines and adiponectin. For
example, RS4-specific significant inverse correlations
were observed between total cholesterol and abundance of Bacteroides plebeius (r = 0.46), Blautia
producta (r = 0.49) and Prevotella stercorea
(r = 0.45). Further research is needed to validate the
associations observed in this cohort and whether they
translate to healthy populations.
In summary, a number of studies have investigated
the influence of RS on gut bacteria. Advances in technology implicate key species such as R. bromii and
E. rectale; however, considerable work remains to
understand the number of species involved (including
lower abundance groups), their interactivities and their
subsequent host interactions, both locally in the gut
and systemically (Lyte et al. 2016). Caution should be
applied when interpreting animal and human studies
as results are not always consistent. For example, only
10% of total variance in human gut microbiota composition has been ascribed to dietary RS (Salonen
et al. 2014), yet the comparable value from murine
© 2016 British Nutrition Foundation
9
studies is 60% (Zhang et al. 2010; Faith et al. 2011).
Future studies in humans should examine the influence
of the various RS types on gut microbiota response.
All future studies should have suitable control groups
and be of adequate length to allow for microbiota
response (Wu et al. 2011), given that changes in
microbiota composition (expressed as alternative
enterotype states) are usually only achieved with dietary modifications lasting at least 10 days (Wu et al.
2011). Other influential factors include sex, genotype,
medical history, medication use, habitual diet, bodyweight status (obesity), level of glycaemic control (diabetes), geographical location and the high degree of
inter-individual variation apparent when studying RS–
gut microbe interactions. Such variation in response is
perhaps unsurprising given that each person has a distinct and highly variable intestinal microbiota (at least
at a species level), although it has been suggested that
a stable core of intestinal microbiota and genes (microbiome) are shared by individuals and may be
related to intestinal function (Martinez et al. 2015). It
has been proposed that any dietary advice on consumption of non-digestible carbohydrates may need to
be personalised (Walker et al. 2011).
Understanding of how RS interacts with gut bacteria is rapidly advancing. For example, new research
comparing gut microbiota metabolites and the host
metabolome in urban vegans and omnivores in the US
suggests that diet has a large impact on metabolome,
but a more modest impact on gut microbiota (Wu
et al. 2016). The authors suggested diet as a substrate
affecting bacterial metabolome rather than as a factor
regulating gut bacteria community membership.
Future studies investigating the influence of RS on gut
bacteria should consider the inclusion of tools such
as metabolomics to try to understand the complexities of how this fermentable starch may influence
bacterial metabolome and biomarkers of bacterial
activity, as well as focusing on bacterial community
membership.
Pre- and probiotics
Prebiotics have been defined as ‘selectively fermentable
ingredients that allow specific changes in the composition and/or activity of the gastrointestinal microbiota
that allow benefits to the host’ (Gibson et al. 2010).
Although various Bifidobacterium strains have been
reported to hydrolyse RS (Crittenden et al. 2001) and
benefits of RS appear related to SCFA production by
colonic bacteria, studies in humans regarding the
potential of RS as a prebiotic compound are limited
10
S. Lockyer and A. P. Nugent
(Martinez et al. 2015). There are three classification
guidelines proposed for prebiotic labelling: (i) resistance to gastric and gastrointestinal digestion; (ii) ability to be fermented and used by gut microbiota; and
(iii) ability to selectively stimulate activity of one, or a
limited number of, gut bacteria with health properties
(Roberfroid et al. 2010). The current literature on RS
does not allow for clear fulfilment of all three of these
criteria. RS by nature is resistant to digestion in the
small intestine and is fermented in the colon where it
may be used by gut bacteria. However, it is not a
homogenous group and it is probable that resistance
to digestion, and most probably fermentation rates,
varies by RS type (Purwani et al. 2012; Zaman &
Sarbini 2016). Currently, the greatest challenge in
defining RS as a prebiotic is proving its ability to
selectively stimulate beneficial microorganisms (Martinez et al. 2015). Additional considerations include the
significant inter-individual variations in gut microbiota
and diet-induced responses, as well as factors such as
age and geography (Br€
ussow 2013). Nevertheless,
interest persists regarding the potential of RS to act as
a fermentable substrate for growth of probiotic
microorganisms; to act in concert with other prebiotics in a synergistic fashion; and/or to enhance the
stability of probiotics, perhaps as part of an encapsulation process or by acting symbiotically with probiotics (Fuentes-Zaragoza et al. 2011). For example, RS
has been coupled with short-chain fructo-oligosaccharides or inulin to increase prebiotic effects (Younes
et al. 2001); co-encapsulated in the region of 1–2% as
a HAMS to enhance the viability of probiotic cultures
(Sultana et al. 2000; Iyer & Kailasapathy 2005); and
used to extend the shelf-life of probiotic cultures in
frozen dairy products (Homayouni et al. 2008). However, further research is needed before RS can be
defined as a prebiotic. This evidence base should
include well-designed human intervention trials involving molecular-based techniques. Finally, it has been
proposed that there is a need for global consensus on
standard procedures to confirm prebiotic potential
using a combination of in vitro and in vivo testing
(Zaman & Sarbini 2016). Such an initiative would
support and standardise the study of RS as a prebiotic
(Zaman & Sarbini 2016).
Colon cancer
Considerable evidence exists suggesting a protective
role of high-fibre diets in colon cancer (SACN 2015).
Fibre is suggested to reduce colon cancer risk by
increasing faecal bulk, reducing transit time and
diluting faecal contents (Aune et al. 2011; Murphy
et al. 2012). In addition to these general benefits, RS
is suggested as a positive influence on colon cancer
risk by stimulating SCFA production, particularly
butyrate. High butyrate production is reported to
reduce colon cancer risk and butyrate treatment of
cultured colon cancer cells can blunt the proliferation
of the cancer cells and stimulate apoptosis (Macfarlane & Macfarlane 2003). Animal studies suggest that
butyrate may reduce colorectal carcinogenesis by
enhancing the apoptotic response to methylating carcinogens (Clarke et al. 2012) and that green banana
flour (RS2) may prevent DNA damage through desmutagenesis and bio-antimutagenesis (Navarro et al.
2015). Proposed mechanisms of action include G-protein activity (GPR 43) and genetic and epigenetic modulation of the Wnt signalling pathway (e.g. inhibition
of histone deacetylation, reduced DNA methylation
and altered expression of miRNA; Fung et al. 2012;
Malcomson et al. 2015). Despite a number of in vitro
and animal studies suggesting that RS reduces colorectal cancer risk, there is less information available from
human trials (Malcomson et al. 2015).
Focusing on cell proliferation as a primary endpoint, two earlier studies with small numbers of
healthy volunteers (n < 14) reported no effect (Wacker
et al. 2002) or decreased cell proliferation (van
Munster et al. 1994) following consumption of RS2
(amylomaize at doses up to 59.7 g/day). Similarly, in
a randomised, placebo-controlled 4-week crossover
trial of 20 healthy volunteers, no robust change in cell
proliferation or DNA methylation was reported following consumption of 25 g of HAMS (12.5 g of
RS2; Worthley et al. 2009). In contrast, reduced cell
proliferation in the upper colonic crypt and differential expression of key cell cycle regulatory genes in 65
adult patients with colorectal cancer has been reported
following consumption of a 30 g/day blend of RS2
(NOVELOSEâ 240 Resistant Starch) and RS3
(NOVELOSEâ 330 Resistant Starch) for 4 weeks
(Dronamraju et al. 2009). Such differences in response
may relate to the health status of the tissue under
study whereby butyrate may increase proliferation in
healthy colonic cells (Malcomson et al. 2015), but
suppress proliferation in cancer cells (Williams et al.
2003). The DNA mismatch repair status of cells may
also determine proliferative response (Dronamraju
et al. 2009). Furthermore, it has also been suggested
that focusing on proliferation in the crypt (one of the
earliest detectable pre-malignant changes) may be
more sensitive than focusing on total cell proliferation
(Malcomson et al. 2015).
© 2016 British Nutrition Foundation
Health effects of resistant starch
To date, two major randomised controlled trials
have investigated the influence of RS on colon cancer
incidence and risk, the CAPP-1 (Burn et al. 2011)
and CAPP-2 studies (Mathers et al. 2012). Both studies were large multi-centre, placebo-controlled trials
in groups at risk of colon cancer. CAPP-1 involved
133 young people (aged 10–21 years) with familial
adenomatous polyposis who were randomised to consume aspirin (600 mg/day) and/or 30 g of RS2 (1:1
blend of potato starch and HAMS; Hylon VII).
CAPP-2 involved over 900 individuals with hereditary
colorectal cancer (Lynch syndrome) who were randomised to consume either 600 mg of aspirin or
aspirin placebo and 30 g of a RS source (RS2:
NOVELOSEâ 240 Resistant Starch and RS3:
NOVELOSEâ 330 Resistant Starch; final dose 13.2 g
of RS/day) or a starch placebo (Amioca waxy starch).
The median follow-up for CAPP-1 was 17 months
and for CAPP-2 52.7 months. In both studies, RS
intake had no clinical effect on polyp number and size
(Burn et al. 2011) or on cancer development (Mathers
et al. 2012).
Such studies highlight the difficulty with translating science from controlled in vitro and animal studies to human clinical trials and the need to reach
consensus on gold standard biomarkers for the indication of colorectal cancer risk. As yet, the influence
of RS on cancer risk in the general population is
unknown. Consideration should be given to the type
of RS and dose in any future clinical trial, as at
least 20 g of RS/day may be needed to increase
stool levels of SCFA (Topping & Clifton 2001). Furthermore, future studies should account for the influence of the gut microbiome on the development of
colon cancer, as different microbial populations have
been identified in observational studies of patients
with colorectal cancer and healthy controls (McCoy
et al. 2013).
Diets rich in red meat have been linked to an
increased risk of colon cancer, particularly in the distal region (Bouvard et al. 2015). Following high meat
consumption and in the absence of fermentable carbohydrates, it is suggested that red meat may undergo
fermentation in the colon and alter the microbiota
composition (Le Leu et al. 2015). Hence, a high-protein, reduced carbohydrate diet may alter the colonic
microbiota favouring a more pro-inflammatory microbiota profile and decreased SCFA production. The
potential of RS to offset this risk, by yielding greater
fibre fermentation in the distal colon and attenuating
red meat-induced colorectal DNA lesions, has recently
been explored (Le Leu et al. 2015). In this study, 23
© 2016 British Nutrition Foundation
11
healthy volunteers consumed 300 g/day of cooked red
meat with or without 40 g of a butyrylated HAMS
(RS4) for 4-week periods in a randomised crossover
design. Inclusion of butyrylated RS4 prevented the
increase in the pro-mutagenic DNA adduct
O6-methyl-2-deoxyguanosine in rectal epithelial cells
observed following the high-red meat diet. Furthermore, inclusion of RS increased stool SCFA concentrations, reduced p-cresol concentrations and induced
more favourable changes in composition of the gut
microbiota (Le Leu et al. 2015). This suggests that
inclusion of RS in the high-meat diet facilitated a
switch from fermentation of protein substrates to carbohydrate substrates (SCFAs), leading to a decrease
in the production of pro-mutagenic adducts that arise
during protein fermentation (Yao et al. 2016). A second proposed mechanism was via increased telomere
length, which can protect against DNA damage. The
potential for RS to attenuate disease risk associated
with high-protein (meat) diets merits further study.
Conditions associated with disturbances in
gastrointestinal function
There is considerable interest in the influence of RS on
disturbances in gastrointestinal function (e.g. constipation and diverticulitis), as well as conditions such as
irritable bowel syndrome (IBS) and inflammatory
bowel diseases (IBD; e.g. ulcerative colitis and Crohn’s
disease). As a component of dietary fibre, RS can contribute to daily fibre intakes deemed adequate for normal laxation in adults [25 g/day according to EFSA
(EFSA Panel on Dietetic Products Nutrition and Allergies 2010a) and 30 g/day according to SACN in the
UK (SACN 2015)], with associated benefits such as
increasing stool bulk (faecal dilution) and consistency
and decreasing transit time and stool pH [for review,
see Maki et al. (2009); Abellan Ruiz et al. (2015);
Nugent (2005)]. For individuals with constipation,
diverticulitis or IBS, for whom fibre intake is an
important part of dietary therapy, RS-containing foods
may make a useful addition to total dietary fibre
intakes.
Disruptive changes in gut microbiota (dysbiosis) and
intestinal host–microbe interactions are reported in
IBD and colorectal cancer, including reduced microbial diversity, particularly in butyrate-producing bacteria (Hu et al. 2016). Furthermore, studies in healthy
children have revealed significant differences in microbial profiles between native African children consuming fibre-rich traditional foods vs. children living in
Europe (De Filippo et al. 2010).
12
S. Lockyer and A. P. Nugent
Animal models suggest that RS3 intake reduces ileal
and colonic inflammatory lesions in wild-type mice
and mice with induced colitis (IL-10-knockout mice),
with roles suggested for IL-10, IFN-c and the transcription factor PPARc (Bassaganya-Riera et al.
2011). In addition, rats fed RS (HAMS, RS2) at 10%
of total diet or in combination with green tea extract
(0.5% GTE) had reduced inflammation assessed by
the expression of COX-2, NF-KB, TNF-a and IL-1b
mRNA and cell proliferation (Hu et al. 2016). However, mixed results have been obtained from two
human randomised controlled trials designed to evaluate the effect of RS on immune function. In one of
these studies, decreases in the cytokines IL-10 and
TNF-a in physically active adults were reported following consumption of a butyrylated HAMS for
4 weeks (West et al. 2013), whereas there were no differences in a panel of other cytokines assessed. Similarly, no influence was seen on high-sensitivity Creactive protein or a panel of 11 cytokines in a trial
involving 17 older adults who consumed 25 g/day
HAMS (HI-MAIZEâ 958 Resistant Starch, ~12.5 g of
RS2) alone or in combination with a probiotic for
4 weeks (Worthley et al. 2009). More recently, the
hypothesis that low-dose RS intake (RS2, Hylon VII
70%, 8.5 g/day for 4 weeks) could decrease intestinal
inflammation was tested in Malawian 3-5 year-old
children (Ordiz et al. 2015). Modest changes in SCFA
production and bacterial populations were noted (increased Actinobacteria and reduced Firmicutes),
although inflammation was not reduced, along with
increased
concentrations
of
calprotectin
and
up-regulation of the bacterial lipopolysaccharide
biosynthesis pathway, both indicators of increased
inflammation (Ordiz et al. 2015). However, there was
no control group in this study and there were no clinical manifestations of increased inflammation. Hence,
the influence of RS on immune function in healthy
populations and in children with existing disease is
unclear.
The benefits of using dietary fibre and RS in the
clinical management of IBD are uncertain. To address
this, fibre intakes and colonic fermentation in patients
with ulcerative colitis in remission following consumption of their habitual diet and when dietary fibre was
increased were compared with the responses of
matched healthy subjects (James et al. 2015). The
intervention involved consumption of foods containing
a high wheat bran–RS mix [12 g of wheat bran and
15 g of RS (RS1 and RS2) per day] or a low wheat
bran–RS mix (2–5 g each of wheat bran and RS per
day) over a 17-day period. RS was combined with
wheat bran to delay fermentation and butyrate production from the proximal to the distal colon and rectum (fermentation at the distal and rectal sites being
of most potential benefit in ulcerative colitis). Total
fibre intake was lower in the ulcerative colitis patients
than in the healthy controls. Encouragingly, the ulcerative colitis patient group tolerated the RS mix and
showed some normalisation of gut transit post-intervention. However, they also displayed a reduced ability to ferment dietary fibre, with intake of the RS and
wheat bran mix having little effect on faecal fermentation patterns or microbiota structure. More studies
specific to this population group are needed (James
et al. 2015).
Oral rehydration solutions
Diarrhoea is a common feature of many gastrointestinal
conditions and severe diarrhoea can cause dehydration,
with associated morbidity and mortality, particularly in
children with acute infectious diarrhoea. Since the
1960s, oral rehydration solutions have been effectively
used to treat dehydration associated with diarrhoea. In
their simplest form, oral rehydration solutions are isomolar, glucose–electrolyte solutions with added base
designed to correct dehydration and metabolic acidosis
(Series 1978). However, simple glucose-based oral rehydration solutions do not reduce the duration or severity
of diarrhoea as they can only correct water loss occurring in the small intestine (Binder et al. 2014). In contrast, RS may be useful in the treatment for diarrhoea
as it is known that SCFAs can enhance fluid and sodium
absorption in the colon, which is an important regulator of water absorption (Ramakrishna et al. 1990;
Monira et al. 2010; Food and Drug Administration
2015). Hence, potential exists to use RS as an adjunct
and/or replacement for glucose in oral rehydration
solutions, providing a low-osmotic source of digestible
glucose and taking advantage of the normal function
of microbial fermentation and SCFAs in electrolyte
and water absorption (Binder 2010; Food and Drug
Administration 2015).
To date, there have been two clinical trials in adults
with cholera, one study in children with non-diarrhoeal
cholera and one in severely malnourished children
with dehydrating cholera (three involving isomolar
and one a hypomolar RS-containing oral rehydration
solution). All tested the effects of HAMS RS2 on
dehydration (Ramakrishna et al. 2000, 2008; Raghupathy et al. 2006; Alam et al. 2009). In three studies,
the oral rehydration solutions containing HAMS were
associated with a 30–50% reduction in time of
© 2016 British Nutrition Foundation
Health effects of resistant starch
occurrence of the first formed stool (Ramakrishna
et al. 2000, 2008; Raghupathy et al. 2006). While
benefits were noted in the study of Alam et al. (2009),
they were not statistically significantly different from
regular oral rehydration solutions. However, it is of
note that this study population included severely malnourished children who also received nutritional supplements (Alam et al. 2009). Other RS forms,
particularly acylated or esterified starches (RS4), for
the treatment of diarrhoea are being considered for
study due to their ability to target SCFA stimulation
in the colon (Binder et al. 2014). Currently, the US
authorities have awarded a ‘Generally Recognised as
Safe’ status to the use of HAMS as an ingredient in
oral rehydration solutions (Food and Drug Administration 2015).
Key points
• RS increases the production of SCFAs in the gut but
there appears to be significant inter-individual variation in responses.
• RS modulates the composition of gut microbiota,
specifically those involved in amylose breakdown and
butyrate and methane production, but responses are
variable and health implications remain to be elucidated.
• There is some evidence that RS can counteract the
detrimental effects of high red meat intake on colorectal cancer risk.
• Emerging evidence suggests a role of RS as an ingredient in oral rehydration solutions.
Role of resistant starch in metabolic
responses – lipid and glucose metabolism,
insulin resistance and prevention of
cardiovascular disease, type 2 diabetes
and metabolic syndrome
This section describes the most recent developments
regarding the influence of RS on markers of metabolic
health in humans. Obesity and type 2 diabetes have
been associated with metabolic and cardiovascular disturbances such as insulin resistance, high blood pressure, chronic low-grade inflammation and abnormal
blood lipid profiles (Stanner 2005). Risk factors for
metabolic health can include genetics and ethnicity, as
well as lifestyle attributes including physical activity
and the diet. The influence of RS on markers of metabolic health is summarised below.
EFSA has recently reviewed the evidence relating
to non-digestible starch (EFSA Panel on Dietetic
© 2016 British Nutrition Foundation
13
Products Nutrition and Allergies 2014a); a commercial RS, HAMS (RS2; EFSA Panel on Dietetic Products Nutrition and Allergies 2011b); and a soluble
fibre with resistant maltodextrin mix (Nutriose 06TM;
EFSA Panel on Dietetic Products Nutrition and Allergies 2014b). These Scientific Opinions sought to find
out whether ‘sufficient evidence exists to establish a
cause and effect relationship between the consumption of foods/beverages containing non-digestible carbohydrates (including RS) and a reduction in
postprandial glycaemic responses, as compared with
foods/beverages containing glycaemic carbohydrates’.
The reviews all concluded that a cause and effect
relationship had been established between the consumption of foods/beverages containing non-digestible
carbohydrates and a reduction in postprandial glycaemic responses, compared with the effect of foods/
beverages containing glycaemic carbohydrates. As
described earlier, conditions of use with respect to
the RS claim include a threshold of 14% replacement
of total starch with RS for a target population of
‘people wishing to reduce their postprandial glycaemic responses’. It remains to be established
whether RS functions independently of simply reducing the total amount of available carbohydrate;
whether glycaemic effects are equal across the various RS types (and food vehicles); whether there are
differences in response of individuals with normal
glycaemic responses and those with type 2 diabetes;
and whether effects on metabolic health go beyond
glucose and insulin metabolism (Robertson 2012a; de
la Hunty & Scott 2014).
Studies on the effects of RS on metabolic health
published after the EFSA opinions are detailed in
Tables S2–S4; the majority of these have focused on
the commercial ingredient HAMS-RS2. A smaller
number of studies have investigated the influence of
RS from bananas/plantain, brown beans, barley,
wheat breads, porridges or rice (Table S3) or novel
RS4 or RS3 ingredients (Table S4). Broadly speaking,
the papers could also be classified into those that
matched the intervention and control foods for available carbohydrate content and those that did not (see
Tables S2–S4), with the majority having a crossover
design, subjects acting as their own controls and short
follow-up periods. Most studies involved healthy individuals without insulin resistance/type 2 diabetes. The
doses of RS ranged from as low as ~1.4 g of RS contained in a serving of bread to ~25 g of RS3
(NOVELOSEâ 330 Resistant Starch) and ~48 g of
commercial RS2 (HAMS-RS2) in a powder form to be
consumed each day.
14
S. Lockyer and A. P. Nugent
In agreement with the EFSA opinion, in studies
where the available carbohydrate content was not
matched, and irrespective of the food vehicle or
RS type involved, RS consumption was generally associated with improved glycaemic outcomes (i.e. reduced
blood glucose and insulin responses). Only three of
the studies that were unmatched for available carbohydrate content failed to see a statistically significant
change in glucose concentrations (Penn-Marshall et al.
2010; Gargari et al. 2015; Sarda et al. 2016). In all
instances, low doses of RS were used (5, 6 and 7.4 g
of RS/day, respectively) over periods of 6–8 weeks,
with intakes at this level unlikely to meet the 14% of
total starch threshold suggested by EFSA. In contrast,
in studies where available carbohydrate contents were
matched the findings were less consistent.
Overall, supplementation with RS can be said to
improve markers of glycaemic control. However, the
magnitude and direction of effect is not always consistent, even within a particular study design. Regarding
blood glucose, effects reported included reduced fasting blood glucose concentrations, reduced postprandial responses (reduced area under the curve) and
enhanced skeletal muscle uptake of glucose (AlTamimi et al. 2010; Johnston et al. 2010; Hallstr€
om
et al. 2011; Karupaiah et al. 2011; Rosen et al. 2011;
Bodinham et al. 2012, 2014; Robertson et al. 2012;
Ekstrom et al. 2013; Ames et al. 2015; Lin et al.
2015; Nilsson et al. 2015; Boll et al. 2016; Gower
et al. 2016; Oladele & Williamson 2016; Sandberg
et al. 2016). However, less clear evidence of benefits
were noted by others (Robertson et al. 2005; Bodinham et al. 2010, 2013; Johnston et al. 2010; Maki
et al. 2012; Lobley et al. 2013). Improvements in
insulin secretion and/or sensitivity have also been
noted (Robertson et al. 2005, 2012; Al-Tamimi et al.
2010; Bodinham et al. 2010, 2013; Haub et al. 2010;
Johnston et al. 2010; Karupaiah et al. 2011; Maki
et al. 2012; Ekstrom et al. 2013; Lin et al. 2015; Nilsson et al. 2015; Gower et al. 2016; Sandberg et al.
2016), but not consistently (Johnston et al. 2010; Bodinham et al. 2012, 2014; Johansson et al. 2013; Lobley et al. 2013). Overall, differences in study design,
primary outcome and study population make drawing
conclusions on efficacy difficult. Acute feeding studies
are helpful in understanding the direct effects of RS
on postprandial glycaemic response to a specific meal
(Robertson et al. 2005; Al-Tamimi et al. 2010; Bodinham et al. 2010, 2013; Haub et al. 2010; Hallstr€
om
et al. 2011; Rosen et al. 2011; Ames et al. 2015; Lin
et al. 2015; Nilsson et al. 2015; Boll et al. 2016;
Oladele & Williamson 2016; Sandberg et al. 2016).
Chronic feeding studies (longer-term interventions
ranging from 4 to 12 weeks) in both healthy populations and individuals with insulin insensitivity/type 2
diabetes are helpful in understanding the influence of
RS on fasting and postprandial glycaemic response
(Robertson et al. 2005, 2012; Johnston et al. 2010;
Penn-Marshall et al. 2010; Bodinham et al. 2012,
2014; Kwak et al. 2012; Maki et al. 2012; GarcıaRodrıguez et al. 2013; Lobley et al. 2013; Gower
et al. 2016). The results of these studies describing the
impact of RS on glycaemic health are summarised in
Tables S2–S4.
The majority of the studies used HAMS-RS2 with
doses ranging from 15 to 48 g, but mainly as 40 g of
RS from HAMS-RS2 (or 67 g of the parent product,
HI-MAIZEâ 260 Resistant Starch) and compared with
27 g of a highly digestible control starch (Amioca).
Forty grams was deemed to be the maximum RS dose
which could be delivered without adverse effects on
taste or texture (Bodinham et al. 2010). Most of the
papers using HAMS-RS2 were published by a single
research group (from the University of Surrey, UK).
RS2 was consumed in these studies as sprinkles (powder), in baked goods (e.g. breads, crackers or muffins)
and in dessert items (e.g. mousse).
The influence of RS types other than HAMS-RS2 on
glycaemic control, matched for available carbohydrate
content, is less well characterised, though studies have
been published on a novel RS4, a novel retrograded
starch, unripe plantains, barley tortillas and a brown
rice variant (Al-Tamimi et al. 2010; Haub et al. 2010;
Karupaiah et al. 2011; Lin et al. 2015; Oladele &
Williamson 2016). RS doses used in these studies were
typically much lower than used for HAMS-RS2 (ranging from 1.4 g/serving to approximately 20 g of RS/
meal), and, in general, positive effects on glycaemic
responses were observed vs. glucose controls, including the one study that compared RS4 with RS2
(HAMS; Haub et al. 2010). Similar findings have been
reported in acute studies where rye, wheat or barley
grains naturally containing RS were incorporated into
breads or porridge, with generally positive effects on
glycaemic responses vs. glucose controls. Again, RS
doses provided were lower than those typically used
with HAMS-RS2 (Hallstr€
om et al. 2011; Rosen et al.
2011; Johansson et al. 2013; Nilsson et al. 2015; Boll
et al. 2016; Sandberg et al. 2016). In the papers identified, responses to RS were smaller in magnitude than
those to oligosaccharides (Boll et al. 2016) or b-glucans (Ames et al. 2015), but appeared to act synergistically with guar gum (Ekstrom et al. 2013). Hence,
the potential may exist for pure RS ingredients to act
© 2016 British Nutrition Foundation
Health effects of resistant starch
in concert with other fibre types to improve glycaemic
control.
Of the studies identified, which included participants at risk of the metabolic syndrome, insulin resistance and/or type 2 diabetes, the majority were longterm in nature and used HAMS-RS2, although one
study used a novel RS4 and another an RS3 ingredient
(NOVELOSEâ 330 Resistant Starch). The effects of
RS consumption on glucose and insulin metabolism as
primary endpoints were variable, but no adverse
effects on glycaemic management were observed
(Penn-Marshall et al. 2010; Bodinham et al. 2012,
2014; Kwak et al. 2012; Robertson et al. 2012;
Garcıa-Rodrıguez et al. 2013). Greater improvements
in glycaemic control were noted following modest
weight loss than following a high-fibre diet that
included either RS (25 g of RS3/day) or NSP (42 g/
day; Lobley et al. 2013), indicating that bodyweight
control remains the primary modifiable factor in glycaemic management.
Currently, the influence of RS on insulin and glucose responses, independent of carbohydrate availability, is not well established. This is partly due to the
methodological challenges in capturing glucose
absorption, clearance and hepatic release (Robertson
2012a).
Furthermore,
different
methodological
approaches can make inter-study comparisons difficult
(e.g. use of minimal model vs. euglycaemic–hyperglycaemic clamps for assessing insulin sensitivity). There
is no evidence to suggest adverse effects of RS on glycaemic control in healthy subjects or in those with
type 2 diabetes, with studies either reporting a benefit
or no response (Nugent 2005). More comprehensive
studies in humans, accounting for normal and insulinresistant phenotypes and responses during challenge
tests, are required before definitive effects and doses
can be defined. Future studies should continue to
account for the fat and protein composition of the test
diets, in addition to available carbohydrate content,
given that these macronutrients can influence glycaemic response (Nugent 2005; Evans 2015). It would
also be helpful to understand whether the benefits
observed with HAMS-RS2 extend to other RS types
in foods with differing physicochemical properties
(e.g. rice and plantain). It is also unknown whether
simultaneous consumption of the various RS forms
has any additive or synergistic effects on glycaemic
control, or indeed the exact influence of RS when consumed alongside other fibre forms. There is some suggestion that the influence of RS on glycaemic control
may be confounded by other constituents in foods
(Oladele & Williamson 2016) and further research is
© 2016 British Nutrition Foundation
15
needed to understand the influence of the food matrix
and subsequent interactions between the RS types,
food matrix and other fibre forms in foods as
consumed.
Influence of resistant starch on other markers of
metabolic health
Metabolic health is influenced not only by glucose
metabolism but also by circulating lipids, hormones
and immune mediators. The balance of evidence does
not suggest a role of RS in mediating lipid metabolism
via total, LDL- or HDL-cholesterol (Robertson et al.
2005, 2012; Johnston et al. 2010; Shimotoyodome
et al. 2011; Bodinham et al. 2012; Kwak et al. 2012;
Gower et al. 2016). However, a recent study found a
significant reduction in total cholesterol and nonHDL-cholesterol after the consumption of a RS-rich
diet vs. a fibre-rich diet for 12 months (see Table S3;
Dodevska et al. 2016). Most studies do not demonstrate an influence of RS on circulating triglycerides in
healthy adults (either fasting or postprandially;
Robertson et al. 2005, 2012; Johnston et al. 2010;
Shimotoyodome et al. 2011; Bodinham et al. 2012;
Kwak et al. 2012; Garcıa-Rodrıguez et al. 2013;
Edwards et al. 2015; Dodevska et al. 2016; Gower
et al. 2016). RS affected triglyceride concentrations in
two studies with type 2 diabetics, albeit in opposing
directions. In the first of these studies, TAG concentrations were reduced by 15% (i.e. associated with
reduced risk; Gargari et al. 2015), while the other
study reported higher fasting TAG in the RS group
(Bodinham et al. 2014; see Table S2). Using sophisticated MRI scanning, the latter study also identified
increased skeletal muscle cellular TAG (soleus intramyocellular triglycerides) after RS consumption,
indicative of increased skeletal muscle uptake of fatty
acids. The increase in soleus intra-myocellular triglycerides occurred despite improvements in glucose tolerance. As noted by the authors, the clinical significance
of the effect is unknown, molecular mechanisms
unclear and sample size very small (n = 12).
Non-esterified fatty acids (NEFA) are vehicles by
which triglycerides, stored in adipose tissue, are transported to the site of utilisation and so are indicative of
lipolysis. Circulating NEFA concentrations are typically reduced by insulin (e.g. after a carbohydrate-containing meal); hence, any improvements in insulin
function may be associated with reductions in NEFAinduced lipolysis. There is some evidence of reduced
circulating NEFA concentrations following RS intake.
For example, one study reported that 12 weeks of
16
S. Lockyer and A. P. Nugent
40 g of RS2 (HAMS-RS2) consumption by participants with type 2 diabetes resulted in reductions in
plasma NEFA concentrations (both in the fasting state
and postprandially), with NEFA levels being inversely
related to soleus intra-myocellular triglycerides (Bodinham et al. 2014). Another study reported that consumption of 30 g of RS2 for 12 weeks by healthy
adults resulted in no change in fasting NEFA levels,
but a decrease in postprandial NEFA concentrations
(Robertson et al. 2005), while a later study reported
decreased skeletal muscle uptake of NEFA in individuals with insulin resistance after an 8-week intervention
of 40 g of RS2/day (Robertson et al. 2012). In other
studies using barley bread, reduced NEFA concentrations were reported the morning after the RS-rich
meal (Johansson et al. 2013), while a similar study
reported the opposite effect (Nilsson et al. 2008). Typically, other studies reported no effects (see Tables S2–
S4; Shimotoyodome et al. 2011; Kwak et al. 2012;
Maki et al. 2012; Garcıa-Rodrıguez et al. 2013;
Edwards et al. 2015; Gower et al. 2016). In summary,
taking the totality of the evidence into account, conclusions cannot be made about how RS influences
NEFA activity. However, there are suggestions from
more comprehensive studies that RS may, at least in
those with type 2 diabetes, improve glucose tolerance
through mechanisms involving increased muscle
uptake of free fatty acids. There is a need to examine
this idea further by comparing individuals with normal and impaired glycaemic responses.
Finally, it should be noted that there is limited evidence suggesting that RS does not influence vascular
function, including peripheral or vascular stiffness
(Johnston et al. 2010), or blood pressure (Kwak et al.
2012; Nichenametla et al. 2014). Furthermore, there
does not appear to be a role of RS in mediating
effects through the activity of the adipose tissue
derived hormones, adipokines, such as adiponectin
(Robertson et al. 2005, 2012; Maki et al. 2012; Bodinham et al. 2014; Gower et al. 2016; Sandberg et al.
2016), leptin (Johnston et al. 2010; Maki et al. 2012;
Robertson et al. 2012) or resistin (Johnston et al.
2010).
Proposed mechanisms/sites of action of resistant
starch
Attempts have been made to understand how RS influences glycaemic control, with putative mechanisms
summarised in Figure 1 and described below. Statistical modelling suggests that HAMS-RS2 supplementation increases first-phase insulin secretion by over a
third (36%; Bodinham et al. 2012). This is significant
given that loss of first-phase insulin secretion is wellcharacterised in type 2 diabetes and targeted by pharmaceutical treatment for this disease. Other studies
have investigated whether RS may benefit peripheral
or hepatic insulin clearance. Two papers suggest that
a reduced postprandial response may be due to
increased hepatic insulin clearance based on higher
C-peptide/insulin ratios (Robertson et al. 2005; Bodinham et al. 2010). However, later studies have not
found evidence for this effect (Bodinham et al. 2012,
2013). Furthermore, Robertson and colleagues have
reported that RS improves peripheral glucose uptake
in the periphery (forearm skeletal muscle), rather than
influencing hepatic production, independently of
changes in bodyweight or macronutrient/energy intake
(Robertson et al. 2005, 2012). However, in a subsequent study by the same group and using the same
methodology, albeit in a diabetic population, there
was no significant effect on hepatic or peripheral
Resistant
starch
Unmatched for available
carbohydrate content
Decreased glycaemic
response due to less
available carbohydrate
content
Matched for available
carbohydrate content
• Influence on glucose and insulin
metabolism; increased glucose uptake in
periphery
• Possible influences of short-chain fatty
acids post-fermentation:
• ↓ lipolysis
• ↓ endotoxaemia and inflammation
• gut hormone production (e.g. ↑
GLP-1 and insulin secretion)
Figure 1 Schematic overview of putative mechanisms of action of resistant starch on glycaemic control
© 2016 British Nutrition Foundation
Health effects of resistant starch
insulin sensitivity and only a trend (P = 0.07) for
greater glucose uptake in the forearm muscle; greater
effects were observed in terms of muscle uptake of
fatty acids (Bodinham et al. 2014). It should be noted
that the latter cohort involved a group of 17 individuals with well-controlled type 2 diabetes using a combination of medications. Additional work is required to
tease out the influence of RS on insulin secretion and/
or sensitivity and establish whether RS mediates
effects peripherally (Bodinham et al. 2014).
RS may have beneficial effects on glycaemic control
through colonic production of SCFAs, then subsequent
absorption, by exerting anti-lipolytic activity; affecting
the activity of gut hormones, such as the incretins
(which stimulate insulin secretion; Delzenne 2005);
and reducing endotoxaemia, thereby reducing markers
of inflammation (Cani et al. 2007).
SCFAs, propionate and acetate (the generation of
which is described in the section on colonic health) are
absorbed from the gut into the circulation and are taken
up into adipose tissue and skeletal muscle tissue where
they are directly associated with improved insulin sensitivity. It has also been proposed that they stimulate
adipose tissue receptors (FFA2/3) and lower NEFA concentrations (and reduced lipolysis) as described above.
Attempts have been made to elucidate how RS may
influence lipolysis at a transcriptional level and there
are some suggestions of increases in genes coding for
enzymes involved in adipocyte differentiation and
mobilisation. For example, in 15 individuals with insulin resistance, HAMS-RS2 (40 g for 8 weeks) consumption increased adipose tissue gene expression (~twofold)
for lipoprotein lipase, adipose triglyceride lipase, perilipin and hormone-sensitive lipase, but not for PPARc
or visfatin (Robertson et al. 2012). In contrast, in a
study of ten healthy adults, intake of 30 g of RS from
HAMS-RS2 did not influence the expression of genes
measured in adipose tissue or skeletal muscle, including
lipoprotein lipase. In this second study, only increased
expression of hormone-sensitive lipase (involved in the
release of stored free fatty acids in adipose tissue) and
insulin receptor substrate-1 (involved in insulin signalling pathways) was noted (Robertson et al. 2005).
Perhaps this lack of effect is unsurprising given the insulin-sensitive nature of the group. More comprehensive
mechanistic studies are needed that account for level of
insulin resistance and any potential site-specific differences between skeletal muscle and adipose tissue.
Animal studies suggest that RS increases glucagonlike peptide-1 (GLP-1) production (Zhou et al. 2008).
In human studies, there are some reports of increased
plasma GLP-1 concentrations following consumption
© 2016 British Nutrition Foundation
17
of RS-containing foods (barley or rye kernel breads;
Nilsson et al. 2008, 2015; Sandberg et al. 2016) and
HAMS-RS2 by individuals with well-controlled type 2
diabetes (Bodinham et al. 2014), though the most
comprehensive study to date does not support a role
of GLP-1 in enhancing insulin sensitivity following
HAMS-RS2 intake in healthy humans (Bodinham
et al. 2013). Interestingly, in a study of 17 individuals
with type 2 diabetes (Bodinham et al. 2014), decreases
in fasting GLP-1 concentrations were observed after
consumption of HAMS-RS2 (40 g/day RS2) for
12 weeks. However, the opposite effect (i.e. increased
GLP-1) was observed during a postprandial challenge.
Given that this increase in GLP-1 occurred alongside
improved glucose disposal and without influencing
insulin response, the authors suggest that this
improved meal handling in people with type 2 diabetes occurred via insulin-independent effects of GLP1 (Bodinham et al. 2014). Such insulin-independent
effects include muscle glucose uptake (Ayala et al.
2009), increased nitric oxide levels altering microvascular recruitment (Chai et al. 2012) and endothelial
function (Nystrom et al. 2004). However, replication
of these results is needed. A number of considerations
have been proposed when studying gut hormone activity in humans. For example, many gut hormones have
short half-lives and are rapidly inactivated (Kim &
Egan 2008). Furthermore, gut hormones do not act
independently (Klosterbuer et al. 2012) and so reliance on a single biomarker may not reveal the complete picture. In addition, most researchers measure
total GLP-1 rather than the active fragment (GLP-1 7–
36; Bodinham et al. 2013). Other potential influencing
factors when assessing GLP-1 activity in humans may
include inter-individual differences in circulating concentrations as a result of defects in the GLP-1 synthesis pathways (Jin 2008) and the influence of high-fibre
diets (Freeland et al. 2010). Overall, unlike animal
studies, the balance of evidence from human studies
does not suggest a role of GLP-1 in mediating glycaemic control, perhaps in part due to differences in
physiology between species but perhaps also due to
inter-individual differences in response and baseline
levels of glycaemic control. Perhaps such variability is
unsurprising given inter-individual responses to SCFA
production after consumption of RS, as noted in the
gut health section of this review.
A third proposed mechanism of RS fermentation on
glycaemic control is reduction in Gram-negative bacteria. It has been suggested that such bacteria can
increase host exposure to lipopolysaccharides, allowing these to enter the bloodstream via a ‘leaky gut’
18
S. Lockyer and A. P. Nugent
and cause low-grade inflammation and insulin resistance [for review, see Keenan et al. (2015b)]. Currently, the only available information relates to animal
studies (Shen et al. 2011), with limited transferability
to humans.
Overall, the literature on RS and metabolic health
mainly focuses on insulin and glucose metabolism
where, in general, RS consumption has been found to
improve glycaemic control. As yet, consistent effects
over and above reductions in total available carbohydrate content require confirmation and studies in populations with normal and impaired glucose tolerance
(including those with type 2 diabetes), accounting for
mechanisms of action where possible. RS does not
appear to cause any adverse effects on metabolic
health in any population group. Given that RS-derived
SCFAs affect insulin sensitivity and lipolysis, and gut
health studies suggest large inter-individual differences
in SCFA production, future studies should capture
inter-individual variability in glycaemic response, as
well as in SCFA production. Furthermore, there is a
need to understand the influence of the food matrix
on glycaemic response and how the various RS types
may act independently, and synergistically, to improve
glycaemic control. The influence of RS on individuals
with impaired glucose tolerance and/or diabetes merits
further study, especially over longer periods of time.
Key points
•
It is well accepted that postprandial glycaemic
responses to RS are reduced compared with digestible
carbohydrates.
• In the EU, there is an approved health claim that
baked products containing at least 14% RS in place of
digestible starch reduce postprandial glycaemia.
• There may be synergism between RS and other fibre
types in reducing glycaemic responses.
• More long-term studies are required to fully ascertain the effect of RS consumption on plasma lipids.
Resistant starch and appetite regulation
Satiation describes the within-meal decline in hunger
and increase in fullness that lead to the inhibition of
further eating, and satiety describes the extent to
which appetite is suppressed between meals (Blundell
et al. 2010). Many factors influence the amount of
food consumed at an eating occasion, including environmental cues, such as portion size; sensory cues,
such as palatability; cognitive factors, such as previous
experiences with that particular food; and metabolic
signals between the gut and the brain, which involve
stretch receptors in the stomach and gut hormones
(Blundell et al. 2010). Peptide YY (PYY), pancreatic
polypeptide (PP), GLP-1 and cholecystokinin (CCK)
are produced in response to eating and suppress appetite and decrease food intake (i.e. increase satiety;
Chaudhri et al. 2006; Troke et al. 2014). Conversely,
ghrelin, known as the ‘hunger hormone’, increases
food intake, is released in the fasted state and suppressed after a meal. The inclusion of foods or ingredients in the diet that decrease hunger and promote
fullness has the potential to prevent weight gain or
even aid weight loss (if the result is lower calorie
intake overall), as hunger is cited as a barrier to the
success of diets undertaken with the aim of losing
weight (L
opez-Nicolas et al. 2016).
Human satiety studies often use a ‘preload’ design,
which involves consumption of the test food or ingredient as a ‘preload’ (the effects of which can be compared with a control preload), which is followed
sometime later by an ad libitum test meal. The effect
of the preload on satiety is assessed by measuring subsequent subjective sensations of appetite and food
intake at the test meal. Sometimes, physiological measurements, such as plasma levels of gut hormones, are
also taken. Ideally, food intake over the rest of the
day (and possibly even the following day) is also measured in order to capture any delayed effects.
Dietary fibre and satiety
There is some evidence that dietary fibre can enhance
satiety, with proposed mechanisms including increased
stomach distension, reduced rate of gastric emptying
and modulation of gut hormone production due to the
formation of a gel in the stomach by some fibre types
(Chambers et al. 2015a). A systematic review published in 2011 reported that in 43% of high-fibre vs.
low-fibre control comparisons, fibre consumption
reduced appetite by at least 10% (Wanders et al.
2011) and a later systematic review reported similar
findings, with 39% of high-fibre treatments significantly reducing appetite compared with low-fibre controls (Clark & Slavin 2013). Overall, these two
reviews suggest that around 60% of studies demonstrate that fibre does not significantly impact on appetite. These same reviews, respectively, indicated that
54% and 22% of fibre interventions reduced subsequent energy intake in an acute setting vs. a control.
Health claim applications submitted to EFSA related
to dietary fibre and effects on satiety, weight management and fat absorption have been rejected on the
© 2016 British Nutrition Foundation
Health effects of resistant starch
grounds that dietary fibre is not sufficiently characterised in relation to the claimed effects (EFSA
Panel on Dietetic Products Nutrition and Allergies
2010c). In its Scientific Opinion, EFSA commented
that the references provided demonstrated varying
effects of different fibre types (i.e. soluble, insoluble,
viscous, non-viscous) on appetite and subsequent food
intake.
Resistant starch, satiety and acute energy intake
In terms of RS, the aforementioned systematic reviews
were in agreement that RS does not influence subjective satiety ratings, but does impact on subsequent
energy intake (Wanders et al. 2011; Clark & Slavin
2013). In general, the numbers of studies testing the
satiating effects of RS tended to be smaller than those
on other fibre types. The Clarke and Slavin review
included four acute RS studies (Nilsson et al. 2008;
Willis et al. 2009; Anderson et al. 2010; Bodinham
et al. 2010), and Wanders et al. included three (Raben
et al. 1994; Willis et al. 2009; Bodinham et al. 2010).
Studies in this area conducted since our last review
(Nugent 2005) are summarised in Table S5, with some
studies also described in Tables S2–S4 (marked with
an asterisk). The number of subjects ranged from 10
to 90, and RS doses ranged from ~2 to 48 g (though
in some papers exact doses are not stated). Most studies assessed the impact of RS consumption on satiety
and food intake over the course of several hours (up
to 1 day) and some studies measured the effect of RS
intake on these parameters on repeated occasions
(Stewart et al. 2010; Sarda et al. 2016). Reported
short-term effects of RS on satiety-related outcomes
have been mixed, with some studies indicating positive
effects (i.e. increased satiety scores, reduced hunger
and/or reduced energy intake; Quilez et al. 2007;
Nilsson et al. 2008, 2013; Anderson et al. 2010;
Bodinham et al. 2010; Johnston et al. 2010; Rosen
et al. 2011; Chiu & Stewart 2013; Harrold et al.
2014; Sandberg et al. 2016), some reporting no effect
of RS on self-reported appetite compared with a control (Nilsson et al. 2008; Stewart et al. 2010; Karalus
et al. 2012; Klosterbuer et al. 2012; Ekstrom et al.
2013; Garcıa-Rodrıguez et al. 2013; Bracken et al.
2014; Gentile et al. 2015; Nilsson et al. 2015), others
reporting no effect on subsequent energy intake compared with a control (Stewart et al. 2010; Klosterbuer
et al. 2012; Karalus et al. 2012) and, in one study,
lower energy intake (~322 kcal over 24 hours) after
RS consumption, but no effect on appetite scores
(Bodinham et al. 2010).
© 2016 British Nutrition Foundation
19
Very small differences in RS content between intervention and control foods (around 1 g or less) may
provide an explanation for the null findings in some
of the satiety studies (Keogh et al. 2006; Ames et al.
2015). Studies with greater doses of RS suggest that
satiety increases with intake of RS. The largest study
identified here (n = 90; Harrold et al. 2014) demonstrated that satiety was sustained for longer following
consumption of 30 g of a composite product [with an
assumed RS content of ~21 g (Ingredion Incorporated
2014)] served within a smoothie vs. an energymatched smoothie containing only 20 g of the same
product (~14 g of RS). In a further study, wheat bread
enriched with 8 g of RS2, barley kernel bread (9.5 g
of RS) and high-amylose barley bread (22 g of RS),
given at evening meals, had no effect on self-reported
satiety vs. standard white wheat bread (1.33 g of RS),
whereas high-b-glucan barley bread (~14% b-glucan,
31 g of RS) resulted in significantly lower satiety ratings after a standard breakfast the next morning
(Nilsson et al. 2008). The higher b-glucan content in
this intervention introduces a confounding variable, a
feature that also limits the interpretation of some of
the other studies described here in which RS was
intentionally combined with other fibre types, such as
guar gum or pullulan, or where intervention foods
were not matched for these components making it
difficult to tease out any effects of RS alone (Keogh
et al. 2006; Klosterbuer et al. 2012; Ekstrom et al.
2013; Harrold et al. 2014; Ames et al. 2015).
A number of potential mechanisms may explain the
effects of RS on satiety and food intake observed in
some studies. A delay in gastric emptying rate (GER),
and possibly the associated delayed and prolonged
presence of glucose in the blood, has been linked to
an increase in satiety (Bergmann et al. 1992; Holt
et al. 1992), though this mechanism may be more relevant to viscous and soluble fibres (RS is neither viscous nor soluble; Marciani et al. 2001; Hoad et al.
2004). Data relating to RS and GER are scarce. The
GER (measured by ultrasonography) of a second meal
preceded by a breakfast containing 13 g of RS was
found not to differ significantly from meals containing just 1 g of RS, though breath hydrogen values
were significantly higher at 6–10 hours (Brighenti
et al. 2006). However, in a study testing eight different bread types, served at an evening meal, the type
with the highest RS content (30.9 g) produced a significantly delayed GER (measured by serum paracetamol) and significantly higher satiety scores and breath
hydrogen after a standard breakfast the following
day. However, the test meals were also higher in b-
20
S. Lockyer and A. P. Nugent
glucan, a soluble fibre (Nilsson et al. 2008). Furthermore, paracetamol is suggested not to be an accurate
measure of gastric emptying (Bartholome et al. 2015).
The effect of RS on GER is therefore unclear at
present.
PYY, PP, GLP-1 and CCK are thought to delay gastric emptying (Troke et al. 2014). RS has been noted
in some studies to increase postprandial GLP-1 (Nilsson et al. 2008, 2015; Johnston et al. 2010; Sandberg
et al. 2016), but not others (Bodinham et al. 2013;
Garcıa-Rodrıguez et al. 2013; Ames et al. 2015). Two
studies have observed an increase in postprandial PYY
after RS consumption in healthy subjects (Nilsson
et al. 2015; Sandberg et al. 2016), whereas two have
found no impact (Garcıa-Rodrıguez et al. 2013; Ames
et al. 2015). Most RS studies have measured only a
few selected gut hormones rather than a broad range,
with very few examining CCK and PP, meaning that
full understanding of the cascade of gut hormone
release in response to RS intake is a long way off
(Klosterbuer et al. 2012). Almost all studies summarised here that measured ghrelin have found that
RS intake has no effect of ghrelin release, apart from
one in which RS consumed in liquid form decreased
ghrelin (Garcıa-Rodrıguez et al. 2013), an interesting
finding considering that a systematic review concluded
that fibre consumed in liquid form is more satiating
(Wanders et al. 2011).
The satiety-enhancing effects of RS have been
measured over short time periods (<3 hours; Quilez
et al. 2007; Anderson et al. 2010; Harrold et al.
2014), and it has been proposed that signals generated by the colonic fermentation of RS, indicated by
increased breath hydrogen or the appearance of
SCFAs, could account for satiety effects observed at
later time points via the reduction of GER, facilitated by gut hormone release (Nilsson et al. 2008;
Harrold et al. 2014). A series of studies demonstrated that the SCFA propionate stimulates the
release of PYY and GLP-1 from gut cells in vitro
and consumption of 10 g/day inulin-propionate ester
in humans increased plasma PYY and GLP-1 and
reduced acute energy intake (Chambers et al. 2014).
Furthermore, intake over a 24-week period was
observed to have beneficial effects on bodyweight,
adiposity and appetite ratings compared with a control (Chambers et al. 2014). While these results may
not be directly applicable to RS, they may be of relevance due to the reported (though varied) production of propionate after RS consumption (see
colonic health section). SCFAs have been shown to
act as ligands for specific receptors that are located
on colonic endocrine cells (known as L-cells), along
with other cells such as adipocytes, and secrete PYY
and GLP-1 (Chambers et al. 2015b). A positive correlation has been found between plasma acetate and
propionate levels and mean GLP-1 concentrations
after the consumption of wholegrain rye kernel
bread vs. a control (Sandberg et al. 2016). If this
mechanism explains the action of RS, the duration
of some of the studies described here may have been
too short to capture any effects, as measurements
ended before SCFAs would have been generated (see
colonic health section). Therefore, for studies that
provide RS at an evening meal or at breakfast, measuring effects on appetite and food intake for up to
15 hours may be necessary (Verbeke et al. 2010). In
addition, because the formation of SCFAs is so variable between individuals due to differences in gut
bacteria and other factors such as transit time
(Chambers et al. 2015b), smaller studies may lack
statistical power to detect an effect.
Interestingly, a portion of boiled rye kernels containing 7.5 g of RS had more of an effect on satiety
and subsequent food intake than a portion of boiled
wheat kernels containing the same amount of RS and
similar amounts of available carbohydrate (Rosen
et al. 2011). The increased satiating effects of rye
could partly be due to the larger portion size (227 g
vs. 172 g of wheat kernels), as food volume can
influence satiety (Keller et al. 2013). Also, the glycaemic profile value (defined in this study as the
duration of the glucose curve divided with the incremental glucose peak) of the rye was almost double
that of the wheat kernels (i.e. the presence of glucose
in the bloodstream was more prolonged). A high glycaemic profile was associated with reduced ghrelin
levels at 270 minutes post-consumption and a lower
desire to eat, which were both associated with lower
energy intake at an ad libitum meal. A high glycaemic profile was also inversely related to insulin
responses including insulinaemic index (defined as the
incremental positive area under the blood insulin
curve after a test product, expressed as a percentage
of the corresponding area after an equi-carbohydrate
reference product taken by the same subject) and
incremental insulin peak, and a low postprandial
insulin response correlated with increased satiety and
lower energy intake. Reduced glucose and/or insulin
responses coupled with either increased satiety,
reduced food intake and/or increases in satiety hormones after the consumption of RS vs. a control
have also been reported elsewhere (Bodinham et al.
2010; Johnston et al. 2010; Luhovyy et al. 2014;
© 2016 British Nutrition Foundation
Health effects of resistant starch
Nilsson et al. 2015). This may be explained by a
prolonged release of gut hormones in response to
prolonged presence of glucose in the blood.
Overall, compared with digestible carbohydrate,
there is some evidence that RS is more satiating and
decreases short-term energy intake, with several plausible mechanisms having been identified, but there are
also a substantial number of studies in which no significant differences have been observed. Inconsistencies
in study design, including type and dose of RS, mean
that it is difficult to draw conclusions from the evidence base and an effective minimum dose is yet to be
identified. When interpreting studies in which foods
with intrinsically higher RS contents are compared
with foods with lower RS contents, it must be remembered that components other than RS (such as protein,
other fibre types) may contribute to observed biological effects. While such studies are informative as they
represent real-life food choices, studies comparing
purified RS-containing products with products otherwise identical in composition but without added RS
are required to understand the specific effects of different types of RS on satiety. Such information could aid
product innovation.
Resistant starch and bodyweight
It seems plausible that if RS is at least as satiating, if
not more satiating, than refined carbohydrates, consumption of RS in part replacement of refined carbohydrates could reduce bodyweight simply because it is
lower in energy. Some animal data indicate that an
RS-rich diet may lead to weight loss (Keenan et al.
2015a). However, the 2015 report from SACN, Carbohydrates and Health (SACN 2015) identified only
three human studies investigating the relationship in
humans (De Roos et al. 1995; Heijnen et al. 1996;
Jenkins et al. 1998) and concluded that there is no significant effect of long-term RS2 and RS3 intake on
overall energy intake (meta-analysis revealed energy
intake differences of +4.4 and 24.6 kcal/day, respectively). SACN did not identify any prospective cohort
studies examining RS intake and health outcomes in
its review.
Studies published since 2005 examining the effect of
long-term RS consumption on bodyweight are summarised in Table S6, with some also detailed in Tables
S2 and S3. The majority reported no change in bodyweight in response to longer term intake of RS, with
doses ranging from 5 to 40 g of RS per day for a
duration of 2–6 weeks. One study provided participants (n = 86; 47% of whom had metabolic
© 2016 British Nutrition Foundation
21
syndrome) with RS4-enriched flour (24 g/100 g, providing ~100 kcal less per 100 g than the control flour)
to use in place of usual flour for the preparation of
foods such as bread, noodles and dumplings for
12 weeks. Consumption of the RS4-enriched flour
resulted in no significant changes in overall bodyweight, but in the metabolic syndrome-free participants a significant reduction in fat mass (0.5%), a
significant increase in fat-free mass (1%) and a 2.6%
reduction in waist circumference occurred (Nichenametla et al. 2014). A significant limitation of this
study is that the mean daily intake of RS was not
reported but the length of the intervention period is a
strength, with EFSA guidance recommending 12
weeks for weight loss intervention studies (EFSA
Panel on Dietetic Products Nutrition and Allergies
2012).
A significant effect of RS on bodyweight (a reduction of 1.6 kg) was reported following consumption of
24 g of native banana starch (dissolved in 240 ml
water, providing 8.16 g of RS) for 4 weeks by 28 participants who were obese and had type 2 diabetes
(Ble-Castillo et al. 2010) vs. a control (24 g of soy
milk in 240 ml water). There was also a significant
reduction in BMI (0.6 kg/m2), but no change in percentage body fat or waist-to-hip ratio, which suggests
that the weight loss may have been due to reduced
body water or loss of lean mass. The energy content
of the intervention and control foods was not provided but the soy milk is assumed to be more calorific
as it contained 46.2% fat. Soy is not ideal to use as a
control food due to its reported bioactive effects
including weight loss, perhaps due to the presence of
phytoestrogens (Zhang et al. 2013). The authors
reported no changes in diet or exercise during the
intervention periods, but the study had no wash-out
period. Overall, it is difficult to drawn firm conclusions from this study due to limitations in study
design.
A study in which overweight and obese subjects
were advised to consume a diet rich in RS-containing
foods for 12 months reported reductions of 4.4 kg,
1.42 kg/m2 and 3.8 cm in weight, BMI and waist circumference, respectively, compared with equivalent
reductions of 2.4 kg, 0.61 kg/m2 and 3.1 cm in the
group following a more general fibre-rich diet
(Dodevska et al. 2016). Subjects in the RS group consumed on average 142 kcal less per day than at baseline compared with a 120 kcal reduction in the fibre
group. This study suggests a positive effect of increasing RS (and indeed all dietary fibre) in the diet over a
long time period on bodyweight.
22
S. Lockyer and A. P. Nugent
Animal studies have suggested that replacing digestible starch with RS can result in lower body fat
and adipocyte size (Higgins 2014; Keenan et al.
2015b). Several mechanisms have been suggested,
including increased energy expenditure and increased
fat oxidation (Keenan et al. 2015b). RS has been
observed to increase postprandial resting energy
expenditure (by more than 70% in the first 3 hours)
and fat oxidation measured by indirect calorimetry
in one human study, an effect that was coupled with
a reduction in the gut hormone GIP (Shimotoyodome et al. 2011). GIP is an incretin released from
the small intestine upon meal ingestion, which stimulates the secretion of glucagon and may have a role
in lipid metabolism and therefore bodyweight,
though the latter effects remain to be established
(Holst et al. 2016). Most human studies have found
either no effect of RS on postprandial energy expenditure (Howe et al. 1996; Keogh et al. 2006; Sands
et al. 2009) or a reduction (Tagliabue et al. 1995),
although the study durations may have been too
short to capture any longer-term effects following
gut fermentation. There has been evidence of
increased fat oxidation in humans after the consumption of RS-enriched foods compared with digestible carbohydrates (Tagliabue et al. 1995; Higgins
et al. 2004; Gentile et al. 2015).
At present, there is little evidence that RS consumption can induce weight loss in humans. Due to the
existence of positive results from animal studies and
some evidence of increased satiety and reduced shortterm energy consumption in humans, this area may be
worthy of further investigation. Further studies should
be at least 12 weeks in duration. In addition, data
from animal studies have suggested that small
decreases in bodyweight can be obscured by the concomitant increase in the mass of gut microbiota,
which may occur with RS supplementation. This, coupled with the impact of losing water weight, means
that body composition should ideally be measured
rather than total bodyweight in order to provide an
accurate assessment of whether or not RS consumption can result in fat loss.
Other health benefits of resistant starch
A small amount of evidence suggests that RS may
have immune modulatory effects, though at present
most data available are from animal and in vitro
studies (Nofrarıas et al. 2007; Bassaganya-Riera et al.
2011; Haenen et al. 2013; Bermudez-Brito et al.
2015). Some human studies have observed that RS
consumption lowers circulating inflammatory cytokines such as IL-6, IL-18 and TNF-a (Nilsson et al.
2008, 2013; Bodinham et al. 2014; Gargari et al.
2015), whereas others have reported no change in
these or other inflammatory markers such as CRP
and PAI-1 (Worthley et al. 2009; Johnston et al.
2010; Penn-Marshall et al. 2010; Kwak et al. 2012;
Maki et al. 2012; Sandberg et al. 2016). It has been
proposed that the mechanism for reduced inflammation is an increase in GLP-2 induced by RS consumption, which decreases intestinal wall permeability and
thus blocks the entry of endotoxins (Nilsson et al.
2013).
A study conducted in subjects with impaired glucose tolerance or newly diagnosed type 2 diabetes
reported that 4-week consumption of rice, delivering
6.51 g of RS/day, reduced markers of oxidative stress
(plasma malondialdehyde and urinary F2-isoprostanes), which was associated with improved endothelial function measured by RH-PAT (Kwak et al.
2012). It was hypothesised that the RS-related reduction in postprandial glycaemia caused reduced production of oxygen-derived free radicals (superoxide
dismutase activity tended to increase after RS consumption), which led to increased serum nitric oxide.
However, in another study, 40 g of RS2 supplementation for 12 weeks had no effect on arterial stiffness
(another measure of vascular function) measured by a
gold standard methodology, pulse wave velocity
(Johnston et al. 2010). More research is clearly
needed in this area.
Emerging research indicates that RS may be useful
in treating chronic kidney disease. In a small study
of nine patients, 40 g of fermentable carbohydrate
per day for 5 weeks shifted nitrogen excretion from
urine into faeces, therefore decreasing uraemia (raised
blood levels of urea and other nitrogenous waste
compounds that are normally eliminated by the kidneys; Younes et al. 2006). Many uraemic substances
are generated by the gut microbiota, and altered
microbial composition and increased intestinal permeability are seen in renal disease (Vaziri 2012). It has
been proposed that RS consumption may yield benefits via the generation of SCFAs and increased proliferation of SCFA-producing bacteria, which may in
turn boost gut barrier integrity and result in reduced
production of waste solutes (Vaziri et al. 2014). In a
study of 28 patients receiving haemodialysis, consumption of 15 g of high-amylose corn starch (60%
RS) per day for 6 weeks resulted in a reduction in
plasma levels of one such solute, indoxyl sulphate
(Sirich et al. 2014).
© 2016 British Nutrition Foundation
Health effects of resistant starch
Key points
•
There is some evidence that RS can decrease appetite and short-term food intake.
• Potential mechanisms include an increase in the
release of gut hormones that promote feelings of satiety, stimulated by SCFAs.
• There is little evidence that RS can decrease adiposity in humans.
• RS may have a role in treating chronic kidney disease.
Conclusion
From a food technology perspective, RS is an established ingredient used in a range of food products
including baked goods, pasta, beverages and dairy
products, as well as for the microencapsulation of
components such as probiotics. In addition, current
evidence points towards RS as a dietary component
with several potential health benefits and no harmful
effects, besides possible gastrointestinal symptoms in
some individuals at high intakes.
The wealth of evidence linking RS to reduced postprandial glycaemic responses has resulted in an EUapproved health claim, which clearly sets out a minimum amount that is needed to replace digestible carbohydrates in order to produce the desired effect.
There is also some evidence of glycaemia-related benefits of RS over and above simply replacing digestible
carbohydrates, but interpretation of these findings is
complicated by differences in study design, study populations, doses and forms of RS used. The role of the
food matrix appears important, where lower doses of
RS may have an effect when naturally present within
foods that contain other types of fibre, rather than as
a purified form. More research among subjects with
diabetes could lead to RS being recommended to this
group as an aid to glycaemic control, especially as no
detrimental effects on glycaemia have been identified.
There is little evidence of effects of RS on lipid metabolism, markers of immune function or adipokines,
although research in these areas is scant at present.
It is clear from animal and in vitro studies that RS
modulates many outcomes related to gut health but
there is difficulty in translating this to humans, perhaps due to inadequacies in the methodologies used at
present. There is evidence that RS can increase the
production of SCFAs in the human gut but there
appears to be a significant degree of variability in
response to RS intervention, most likely influenced by
differing gut microbial compositions between
© 2016 British Nutrition Foundation
23
individuals, habitual intake, RS type and presence or
absence of other RS and other fibre types. Furthermore, SCFAs use by the host within the colon prior to
excretion can be influenced by sex, BMI and gut
microbiota. More data in this area would be useful as
this is an important point for researchers to consider
when undertaking power calculations for studies using
RS. Esterified RS4 may be more effective at generating
SCFAs than native RS.
There is good evidence that RS influences gut microbial communities involved in amylose breakdown and
butyrate and methane production, but there is a significant variability in responses. Advances in gut microbe
profiling and metabolomics may help us to understand
the complexity of this variation. If stimulatory effects
are found to be selective in favour of bacteria that
promote health benefits, this could lead to the classification of RS as a prebiotic which is not possible at
present. The potential for RS to act synergistically
with other fibre types and probiotics merits further
attention. While there is no evidence for an effect of
RS on colorectal cancer occurrence or polyp number
and size in individuals at high risk, there is evidence
of a reduction in disease risk markers at a molecular
level and for mitigation by RS intake of the detrimental effects of red meat on colorectal cancer. Emerging
research also indicates a role of RS in treating
dehydration.
There is some evidence that RS can positively influence satiety and short-term food intake and plausible
biological mechanisms have been demonstrated, but
results have not been consistent. Studies that have
measured appetite as a secondary endpoint have sometimes used flawed study designs. For example, information on the effect of RS on glycaemic responses has
been provided by matching an RS-rich test food and
control food for carbohydrate content, but this can
make comparisons of appetite effects difficult due to
the introduction of other factors that impact on satiety, such as differences in portion sizes. There is some
evidence of potential synergistic effects of RS with
other fibre types leading to enhanced satiety effects,
which requires further study.
The duration of RS satiety studies published to date
varies significantly, with some studies providing RS in
an evening meal and measuring next day effects on
appetite to allow time for SCFA generation, while
others have taken measurements for only a few hours
after RS consumption. Individual differences in SCFA
production should also be taken into account in these
types of studies. The EU-funded SATIN (SATiety
INnovation) project is looking into the effect of food
24
S. Lockyer and A. P. Nugent
components, including RS, on satiety and weight loss,
with the aim of increasing understanding of the
biopsychological mechanisms underpinning satiety
(www.satin-satiety.eu). Outputs from this project
could help to inform methodologies for future studies
examining the impact of RS and appetite regulation.
Currently, there is very little evidence in humans that
any satiating effects of RS translate into weight loss.
This is an area worthy of investigation with welldesigned studies of sufficient duration and robust dietary assessment.
There may be a lot still to be discovered in terms of
the health benefits of RS. At the time of writing,
upcoming trials investigating the effect of RS on bodyweight, gut health, glycaemia, insulin sensitivity, CVD
risk markers, appetite and colorectal cancer prevention, in a variety of populations including patients
with Parkinson’s disease, type 2 diabetes, renal diseases and those undergoing transplantation, have been
registered on clinicaltrials.gov. At present, most RS
research relates to RS2. A wider spread of evidence
relating to all RS types, via the testing of whole foods,
would be useful in informing innovation, the selection
of grains/varieties of RS-rich foods and perhaps in
future, a recommended intake value for RS.
Conflict of interest
The British Nutrition Foundation is grateful to Ingredion Incorporated for financially supporting some of
the time spent on the preparation of this review. The
views expressed are those of the authors alone.
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Supporting Information
Additional Supporting Information may be found in
the online version of this article:
Table S1. Overview of studies post 2005 exploring the
effect of resistant starch on gut health in humans.
Table S2. Summary of acute, semi-acute and chronic
studies (post 2005) investigating the influence of high
amylose maize starch (HAMS) on markers of metabolic health in humans.
Table S3. Summary of acute, semi-acute and chronic
studies (post 2005) investigating the influence of resistant starch from banana, bread, beans and rice on
markers of metabolic health in humans.
Table S4. Summary of acute, semi-acute and chronic
studies (post 2005) investigating the influence of RS3
and RS4 on markers of metabolic health in humans.
Table S5. Studies (post 2005) investigating the effect
of resistant starch on appetite and short-term energy
intake in humans.
Table S6. Studies (post 2005) investigating the effect
of resistant starch on bodyweight in humans.
© 2016 British Nutrition Foundation