Food Science and Technology Bulletin - Functional Foods, Volume 1

107 Pages·2005·2.52 MB·107\107

by  Gibson, Glenn R. (Eds.)

TM
Food Science and Technology Bulletin

Functional Foods

Volume 1

CHIEF EDITOR

Professor Glenn R. Gibson
The University of Reading
Reading
UK

EDITORIAL ADVISORY BOARD 2005

Dr Edward Farnworth Dr Colette Shortt
Food Research and Development Centre Yakult UK
St. Hyacinthe London
Canada UK

Dr David P. Richardson Dr Tiina Mattila-Sandholm
dprnutrition Valio Ltd
Croydon Finland
UK
Food Science and Technology Bulletin: Functional Foods comprises a minimum of eight minireviews per
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ISSN 1476-2137
ISBN 0 86014 193 4

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Contents
1. Functional Foods, Blood Lipids and Coronary Heart Disease ............................... 1-1
1.1 Coronary Heart Disease and Risk Factors ....................................................................... 1-1
1.2 Effects of Probiotics on Blood Lipids: the Evidence ......................................................... 1-2
1.3 The Effect of Fructan-type Oligosaccharide Prebiotics on Lipid Metabolism in
Humans ............................................................................................................................ 1-5
1.4 The Effects of Synbiotics on Coronary Heart Disease ..................................................... 1-9
1.5 References ....................................................................................................................... 1-9
2. Gastrointestinal Infections and the Protective Role of Probiotics and
Prebiotics .................................................................................................................... 2-1
2.1 Introduction ...................................................................................................................... 2-1
2.2 Acute Pathogenesis in the Human Gut ............................................................................ 2-1
2.3 Chronic Gut Disorder ....................................................................................................... 2-2
2.4 Functions of the Normal Human Gut Microbiota .............................................................. 2-4
2.5 Probiotics and Prebiotics .................................................................................................. 2-5
2.6 Examples of Foodstuffs Containing Probiotics and Prebiotics ......................................... 2-7
2.7 Mechanisms of Effects of Probiotics and Prebiotics on Gastrointestinal Pathogens ....... 2-8
2.8 Conclusions ...................................................................................................................... 2-11
2.9 References ....................................................................................................................... 2-11
3. Functional Foods and Bowel Cancer ........................................................................ 3-1
3.1 Introduction ...................................................................................................................... 3-1
3.2 The Biology of Cancer ...................................................................................................... 3-1
3.3 Diet as a Risk Factor ........................................................................................................ 3-2
3.4 Functional Foods – Modifying the Intraluminal Environment ........................................... 3-2
3.5 Phytochemicals – Foodborne Anticarcinogens ................................................................ 3-4
3.6 Polyunsaturated Fatty Acids (PUFAs) .............................................................................. 3-6
3.7 Conclusion ....................................................................................................................... 3-7
3.8 References ....................................................................................................................... 3-7
4. Functional Foods: Dietary Intervention Strategies in Autistic Spectrum
Disorders ..................................................................................................................... 4-1
4.1 Introduction ...................................................................................................................... 4-1
4.2 Functional Foods .............................................................................................................. 4-1
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vi Contents
4.3 What Is Autism? ............................................................................................................... 4-2
4.4 Interventions in Autism: Gluten and Casein Removal ...................................................... 4-2
4.5 Interventions in Autism: Phenolic Food Components and Enzymes ................................ 4-3
4.6 Interventions in Autism: the Gut Microflora ...................................................................... 4-4
4.7 Conclusions ...................................................................................................................... 4-7
4.8 References ....................................................................................................................... 4-8
5. From Hypoallergenic Foods to Anti-allergenic Foods ............................................ 5-1
5.1 Introduction ...................................................................................................................... 5-1
5.2 Allergy, Atopy and the Origin of Allergic Disease ............................................................. 5-1
5.3 Normal Intestinal Microflora ............................................................................................. 5-4
5.4 Inflammation ..................................................................................................................... 5-5
5.5 Current Prevention Strategies and Treatment of Allergy ................................................. 5-6
5.6 Functional Foods .............................................................................................................. 5-6
5.7 Potential of Functional Foods for Allergic Individuals ....................................................... 5-8
5.8 Future Prospects .............................................................................................................. 5-8
5.9 Conclusions ...................................................................................................................... 5-8
5.10 Acknowledgements .......................................................................................................... 5-9
5.11 References ....................................................................................................................... 5-9
6. Canine Functional Foods ........................................................................................... 6-1
6.1 Introduction ...................................................................................................................... 6-1
6.2 Functional Food Types ..................................................................................................... 6-1
6.3 Colon-targeted Functional Foods ..................................................................................... 6-2
6.4 Conclusion ....................................................................................................................... 6-7
6.5 References ....................................................................................................................... 6-7
7. Perspectives on Foods for Specific Health Uses (FOSHU) ..................................... 7-1
7.1 Introduction ...................................................................................................................... 7-1
7.2 Drivers Behind FOSHU .................................................................................................... 7-1
7.3 How FOSHU Status Is Granted ....................................................................................... 7-2
7.4 Current Products .............................................................................................................. 7-3
7.5 Consumer Reaction ......................................................................................................... 7-6
7.6 Conclusions ...................................................................................................................... 7-7
7.7 References ....................................................................................................................... 7-8
8. Functional Foods in the USA: Emphasis on Probiotic Foods ................................ 8-1
8.1 Introduction ...................................................................................................................... 8-1
8.2 Probiotics – the Potential ................................................................................................. 8-2
8.3 Ensuring the Authenticity of Probiotic Products ............................................................... 8-3
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Contents vii
8.4 Product Labelling Claims for Probiotic Products .............................................................. 8-6
8.5 Conclusions ...................................................................................................................... 8-8
8.6 References ....................................................................................................................... 8-8
9. Functional Foods in Infant Formulae ........................................................................ 9-1
9.1 Introduction ...................................................................................................................... 9-1
9.2 Neonatal Gut Microflora ................................................................................................... 9-2
9.3 The Gut Microflora of Breast-fed and Formula-fed Infants ............................................... 9-2
9.4 The Search for Breast Milk Substitutes ............................................................................ 9-3
9.5 Conclusions ...................................................................................................................... 9-9
9.6 References ....................................................................................................................... 9-10
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Functional foods, blood lipids and coronary heart disease

Kim G Jackson and Julie A Lovegrove
Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, The University of Reading, Whiteknights, PO Box 226,
Reading RG6 6AP, UK. Tel. [phone]. Fax [phone].
E-mail [email protected]

Abstract

For the past 20 years, the principal focus of public health strategies for reducing the risk of coronary heart
disease (CHD) has been aimed at lowering serum cholesterol levels. However, recent findings have highlighted
not only cholesterol but also triacylglycerol as a significant lipid risk factor for CHD. Dietary strategies which
are able to reduce these circulating lipid levels and which are able to offer long-term efficacy comparable with
effective drug treatments are currently being sought. One dietary strategy that may benefit the lipid profile
involves supplementation of the diet with prebiotics, probiotics and synbiotics; this method improves the health
of the host by supplementation with and/or fortification of certain health promoting bacteria present in the
gastrointestinal tract, by dietary means. Probiotics (live organisms) in the form of fermented milk products have
been shown to exert cholesterol lowering properties, whereas non-digestible fermentable carbohydrate
prebiotics have been shown to reduce triacylglycerol levels in animal studies. However, in human studies using
both prebiotics and probiotics, there have been inconsistent findings with respect to changes in lipid levels,
although, on the whole, there have been favourable outcomes.

Keywords: cholesterol, fermented milk products, fructans, glucose, insulin, prebiotics, probiotics, synbiotics,
triacylglycerols

Abbreviations: CHD, coronary heart disease; GIP, glucose-dependent insulinotrophic polypeptide; GLP-1,
glucagon-like peptide-1; HDL, high-density lipoprotein; LDL, low-density lipoprotein; OFS, oligofructose;
TAG, triacylglycerol; VLDL, very low-density lipoprotein

1. Coronary heart disease and risk factors thrombus or clot may further occlude the artery, with the

latter being an acute event which causes a myocardial
Diseases of the circulatory system account for an
infarct (Mangiapane and Salter 1999).
appreciable proportion of total morbidity and mortality in
CHD is a multifaceted condition which has no one single
adults worldwide. Coronary heart disease (CHD) accounts
cause. Potential risk factors are being identified
for around 115 000 deaths each year in the United Kingdom
concurrently with progress in CHD research. The known
alone (Department of Health 1999). The rates of mortality
risk factors for development of CHD are shown in Table 1.
due to CHD vary considerably throughout the world; for
This review is mainly concerned with blood lipids and CHD
example, in Finland, the annual incident rate has been
risk. Epidemiological studies examining CHD risks in
reported to be thirteen times higher than that reported in
different populations have observed a positive correlation
Japan (Keys 1980). The incidence rate is reducing in most
between fasting cholesterol levels in individuals, especially
countries, although in Eastern Europe and developing
that of low-density lipoprotein (LDL) cholesterol, and the
countries, CHD is still increasing in incidence.
development of CHD (Keys 1970). The role of cholesterol
The underlying basis for clinical cardiovascular disease is
reduction as a public health strategy in the primary
a combination of atherosclerosis and thrombosis
prevention of CHD was unequivocally supported by the
(Mangiapane and Salter 1999). Atherosclerosis is a
findings of the West Scotland Heart Study (Shepherd et al.
condition in which the arterial lining is thickened in certain
1995). However, in addition to plasma cholesterol (a classic
locations by raised plaques which occur as a result of the
risk factor) other lipid risk factors have also been identified.
excessive accumulation of modified lipids (predominantly
These include low levels of high-density lipoprotein (HDL)
cholesterol), and of proliferation and migration of smooth

muscle cells from deeper layers within the arterial wall.
Formation of an atherosclerotic plaque can occlude one or Food Science and Technology Bulletin: Functional Foods 1 (1) 1–11
more arteries, mainly coronary and cerebral, resulting in DOI: 10.1616/1476-2137.3965. Published 8 May 2002
ISSN 1476-2137 © IFIS Publishing 2002. All Rights Reserved
CHD or a stroke, respectively. In addition, a superimposed
1 - 2 Functional foods, blood lipids and coronary heart disease K. G. Jackson and J. A. Lovegrove

2.1 Evidence from the Maasi
Table 1. Risk factors for the development of coronary
heart disease Mann and Spoerry (1974) investigated the effect of an
exogenous surfactant material, known to be
Unmodifiable Gender (male) hypercholesterolaemic, in 24 male Maasi warriors.
Increasing age Although a significant fall (9.8%) in serum cholesterol was
Genetic traits (including lipid metabolism reported, because of a number of confounding factors

abnormalities) including the introduction of an exercise programme,
Body build coupled with an inability to control food intake and subject
weight gain, this study is now considered simply as a
Ethnic origin
curiosity and does not lend much to overall findings.
Modifiable Cigarette smoking

Some hyperlipidaemias (increased plasma cholesterol 2.2 Evidence for the milk factor
and triacylglycerol)
Low levels of high-density lipoprotein (HDL) As a follow-up to the Maasi trial, Mann (1977) fed a small
group (n = 4) of US volunteers 4 l of yoghurt
Obesity
(microbiological activity unspecified) per day over a 12-day
Hypertension
period, and reported a significant fall of 37% in serum
Low physical activity cholesterol. When the intake of the yoghurt was reduced to
Increased thrombosis (ability to clot) 2 l per day, this hypocholesterolaemic effect was
maintained, although intake of 1 l per day resulted in a
Stress
return to baseline cholesterol levels. The rate of cholesterol
Alcohol consumption
biosynthesis was monitored by measuring specific activity
Diseases Diabetes (glucose intolerance) of plasma digitonin-precipitated sterols, 2 h after a pulse of
Geography Climate and season (cold weather) [14C] acetate. A 28% fall in acetate incorporation was
reported 16 days after a 12 day ingestion of the high
Soft drinking water
yoghurt dose (4 l per day). To help explain the fall in serum

cholesterol, Mann proposed the presence of a milk factor
cholesterol (Gensini et al. 1998), an elevated concentration
such as hydroxymethyl glutarate (an inhibitor of 3 hydroxy-
of triacylglycerol (TAG; a major fat in the blood) in both
methyl-glutaryl CoA reductase which is an important
the fasted and fed (postprandial) states (Austin, 1991; Karpe
enzyme involved with cholesterol synthesis in the liver).
et al. 1994; Wilson 1994) and insulin resistance (Reaven et
Drinking milk has also been shown to be associated with
al. 1993; Haffner et al. 1999).
reduced mortality from CHD. At least seven prospective
There is a substantial, diverse, and generally consistent
cohort studies have investigated the effect of milk
body of evidence linking diet and CHD. Current dietary
consumption on death from CHD. The body of evidence
strategies for the prevention of CHD advocate adherence to
suggests that drinking milk is not detrimental and may be
low-fat/low-saturated-fat diets (Department of Health
mildly protective against CHD (Ness et al. 2001).
1994). Although there is no doubt that, under certain
Intervention studies on milk and plasma cholesterol levels
experimental conditions, low-fat diets do offer an effective
are mixed: some studies show beneficial reductions of LDL-
means of reducing blood cholesterol, on a population basis
cholesterol after three daily servings of low-fat milk (Barr et
they appear to be less effective. This is largely due to poor
al. 2000; Obarzanek et al. 2001), while others do not
compliance attributed to the poor palatability and
(Buonopane et al. 1992). The general consensus is that milk
acceptability of such diets to the consumer. Attempts have
consumption per se does not increase CHD risk, but neither
therefore been made to identify other dietary components
does it consistently reduce lipid risk factors.
which can address lipid abnormalities associated with CHD.
Howard and Marks (1979) investigated candidates for the
Recently, dietary intervention strategies based around
milk factor and fed lactose (with or without Ca/Mg), cheese
probiotics and prebiotics have been used with varying
whey or yoghurt to volunteers over a 2 wk period. The
degrees of success in lowering plasma cholesterol and TAG
yoghurt alone significantly reduced plasma cholesterol by
levels.
5.5%. However, this trial was also subject to the same

problems of lack of dietary control as the Mann and Spoerry
2. Effects of probiotics on blood lipids: the evidence
study, with substantial changes from the volunteers’

habitual diet resulting in a number of confounding factors.
A probiotic has been recently redefined as 'a live microbial
Unfortunately, most of the early studies introduced
food ingredient that is beneficial to health' (Salminen et al.
confounding factors due to a lack of control in the subjects'
1998). Since the early 1970s, research into probiotics and
diet. Hepner and colleagues (1979) performed a study
CHD risk has increased dramatically, although to date the
which attempted to control for such factors. This
data have been inconsistent and inconclusive (Table 2).
investigation was a crossover study in which 720 ml of

yoghurt and 750 ml milk were given to the subjects over a
Functional foods, blood lipids and coronary heart disease K. G. Jackson and J. A. Lovegrove 1 - 3
Table 2. Summary of human studies to evaluate the hypocholesterolaemic properties of fermented milk
products
Author Subjects (n) Product (vol/type) Duration Total cholesterol LDL cholesterol
Mann et al. (1974) 24M 8.3 l lacto/yoghurt 3 weeks -9.6% (P<0.001) NA
Mann (1977) 3M 1F 4 l WMY 12 days -16.8% (P<0.05) NA
Mann (1977) 3M 2F 2l SMY 12 days -23.2% (P<0.05) NA
Howard et al. (1979) 10 3 l 3 weeks 5.5% (P<0.05) NA
Hepner et al. (1979) 6M 4F 720 ml (A) 4 weeks -5.4% (P<0.01) NA
Hepner et al. (1979) 5M 3F 720 ml (B) 4 weeks 8.9% (P<0.01) NA
Rossouw et al. (1979) 11M 2 l yoghurt 3 weeks +16% (P<0.01) +12% (P<0.001)
Thompson et al. (1982) 13 11 UPY 3 weeks NS NS
Bazzare et al. (1983) 5M 16F 550 g yoghurt 1 week -8.7% NA NA
Massay (1984) 30F 480 ml yoghurt 4 weeks NS NS
Jaspers et al. (1984) 10M 681 g yoghurt 2 weeks -11.6% transient (P<0.05) NS
McNamara et al. (1989) 18M 16 oz LFY 4 weeks NS NS
Agerbaek et al. (1995) 58M 200 ml UPY 6 weeks -6.1% (P<0.001) -9.8% (P<0.001)
-9% transient
Richelsen et al. (1996) 47M 43F 200 ml UPY 21 weeks NA
(P<0.05)
Sessions et al. (1997) 78M 76F 200 ml UPY 12 weeks NS NS
Bertolami et al. (1999) 11M 21F 200 ml UPY 8 weeks -5.3% (P<0.004) 6.2% (P<0.001)
De Roos et al. (1999) 78 500 ml UPY 6 weeks NS NS
Agerholm-Larsen et al. (2000) 20M 50F 450 ml UPY 8 weeks NS -8.4% (P<0.05)
F, female; M, male; WMY, whole milk yoghurt; UPY, unpasteurised yoghurt; SMY, skimmed milk yoghurt; PY, pasteurised yoghurt; LFY, low
fat yoghurt; NA, data not available; NS, not statistically significant.

Adapted from Taylor & Williams 1998

2.3 Probiotic effect on lipid parameters

4 wk period. Significant reductions in plasma cholesterol
Hepner et al. (1979) assessed whether the presence of live
were observed after the first week of both supplementation
bacteria was important for reported effects of yoghurt on
periods (Hepner et al. 1979). The observation that
lipid parameters. The aim of the study was to compare the
cholesterol levels could fall significantly after acceptance
effects of 750 ml of pasteurised and unpasteurised yoghurt,
onto a study has been well documented (Rossouw et al.
using milk as the placebo. After a 12 wk intervention
1981; Sessions et al. 1997). This is probably due to a
period, all treatments significantly reduced plasma
conscious or even subconscious modification of the diet by
cholesterol, with milk resulting in a lesser reduction.
the volunteers due to awareness of dietary assessment. In an
Unfortunately, the nutritional and microbiological content
attempt to reduce this confounding factor, baseline run-in
of the products used was not reported which severely
periods are essential (Sessions et al. 1997). Of the early
hampers comparison with other study data. Thompson et al.
negative studies that have been published, those of
(1982) analysed a wide range of milk-based products
Thompson et al. (1982), Massey (1984) and McNamara et
including milk fortified with Lactobacillus acidophilus (titre
al. (1989) have incorporated a run-in period. The study of
1.3 x 107 counts/ml), buttermilk (a milk product fermented
McNamara et al. was one that was more carefully
with Streptococcus cremoris and Streptococcus lactis - titre
controlled. They investigated effects of the ingestion of 480
6.4 x 108 counts/ml) and a yoghurt (fermented with
ml unspecified yoghurt and reported no significant
Lactobacillus bulgaricus and Streptococcus thermophilus -
cholesterol reduction. From the evidence presented above, it
titre 1.2 x 109 counts/ml). A 1 l supplement was offered for
can therefore be concluded that there is little evidence that
a 3 wk period, but no significant changes were reported in
milk or fermented milk products affect serum lipid
serum total cholesterol, LDL or HDL. Another study (De
parameters per se.
Roos et al. 1999) involving seventy-eight male and female
1 - 4 Functional foods, blood lipids and coronary heart disease K. G. Jackson and J. A. Lovegrove
participants (mean cholesterol 5.4 ± 0.7 mmol/l) clinically important (Bertolami et al. 1999). A more recent
investigated the effect of consuming 500 ml of control publication investigated the effects of consumption of a
yoghurt or yoghurt enriched with Lactobacillus acidophilus larger volume (450 ml per day) of GAIO® yoghurt
L-1 for a 6 wk period. No significant reduction in containing the CAUSIDO® culture on seventy overweight
cholesterol or LDL cholesterol was reported in this study. and obese men and women for 8 wk. After adjustment for
The possible importance of variation in yoghurt cultures changes in body weight, a significant reduction in LDL-
stimulated Jasper et al. (1984) to assess the effect on plasma cholesterol (8.4%) was reported in the GAIO® group
lipid levels of consuming 681 g per day of different samples (Agerholm-Larsen et al. 2000a).
of a non-fat unpasteurised yoghurt fermented with a 1:1 However, not all studies have reported a significant
ratio of Lactobacillus bulgaricus and Streptococcus reduction in cholesterol after GAIO® ingestion. One study
thermophilus. Two yoghurt strains (CH-I and CH-II) were reported by Sessions et al. (1997) was conducted in 160
taken for a 14 day period each, followed by a third strain middle-aged men and women with moderately raised
(SH-III) which was taken for 21 days. A 21 day 'washout cholesterol. Volunteers consumed 200 ml per day of either
period' was permitted between each dietary intervention the active (containing a minimum titre of 1 x 106 counts/ml)
period to re-establish normal serum cholesterol levels. or chemically fermented yoghurt for a 12 wk period.
Significant falls in serum total cholesterol and LDL Stratified randomisation was used and the study was well
cholesterol levels occurred after 1 wk with strain CH-II and controlled. During the 2 wk run-in period, both groups
2 wk with strain SH-III. Such transient changes could be showed significant reductions in blood cholesterol (P <
explained either by effects of volunteers commencing the 0.05), but thereafter there were no further changes in either
study as discussed previously, or could be a true difference group or between the groups at any of the time points.
between the efficacious properties of different strains and A meta-analysis of short-term intervention studies using
indeed different types of probiotics. GAIO® was published by Agerholm-Larsen et al. (2000b).
A commercially available yoghurt, GAIO®, containing a They concluded that consumption of the fermented yoghurt
specific bacterial culture, CAUSIDO® (consisting of produced 4 and 5% decreases in total and LDL cholesterol
Enterococcus faecium and Streptococcus thermophilus, and respectively; however, long-term studies were required to
has been shown to have hypocholesterolaemic properties demonstrate sustained effects on blood lipids.
when tested on animals) has been studied, albeit with
inconsistent findings. Agerbaek et al. (1995) tested the 2.4 Possible mechanisms of action

effect of GAIO® against an identical yoghurt that had been
It is important to highlight the fact that viable and
chemically fermented with an organic acid (δ-gluco-
biologically active microorganisms are usually required at a
lactone). Fifty-eight middle-aged men with moderately
specific target site in the host. It is therefore essential that
raised cholesterol levels (5.0-6.5 mmol/l) were fed 200 ml
the probiotics involved not only exert the characteristics that
per day of yoghurt for a 6-wk period. They observed a 9.8%
are necessary to produce any desired biological effects, but
reduction in LDL cholesterol levels (P < 0.001) for the live
also have the required viability and are able to withstand the
yoghurt group. Although this was a well-controlled study,
host's natural barriers against ingested bacteria. The classic
an unforeseen skew in randomisation resulted in a
yoghurt bacteria, Streptococcus thermophilus and
significantly different baseline total and LDL cholesterol
Lactobacillus bulgaricus are technologically effective, but
levels in the two groups. The reduction in these parameters
they do not reach the lower intestinal tract in a viable form.
observed in the live yoghurt group could be ascribed to a
Therefore, intrinsic microbiological properties, such as
regression towards the mean. Another study performed
tolerance to gastric acid, bile and pancreatic juice, are
using the same yoghurt and a similar design for a longer
important factors when probiotic organisms are considered
period (6 months) was carried out in 87 men and women
(Huis In't Veld and Shortt 1996).
aged between 50 and 70 years (Richelsen et al. 1996).
The mechanism of action of probiotics on cholesterol
Although after 12 wk there was a significant drop in LDL
reduction is unclear, although a number of possible
cholesterol levels in the group taking the active yoghurt,
mechanisms have been proposed. These include the
these reductions were not sustained. This was partly
physiological actions of fermentation end products (short
explained by a reduction in the titre of the yoghurt at 12 wk.
chain fatty acids), deconjugation of bile acids (which could
A more recent study investigated the same product at 200 g
reduce cholesterol by co-precipitation at acidic pH or by
per day for 8 wk with 32 patients who had mild to moderate
increasing excretion of bile acids, thereby increasing the
hypercholesterolaemia. The patients were asked to follow a
amount of cholesterol required for de novo synthesis in the
lipid-lowering diet for 8 wk and then were given the test or
liver, or a combination of both these mechanisms),
control product for two 8 wk periods. The results from this
cholesterol assimilation, and cholesterol binding to bacterial
study showed a significant reduction (5.3% (P = 0.004) and
cell walls. The short chain fatty acids that are produced by
6.2% (P = 0.01), respectively) in total and LDL cholesterol
bacterial anaerobic breakdown of carbohydrate are acetic,
after consumption of the active product. However, the
propionic and butyric acids. The physiological effects of
authors did question whether or not an average reduction of
these are discussed in more detail in the prebiotic section
approximately 5% for total and LDL cholesterol was
below.
Functional foods, blood lipids and coronary heart disease K. G. Jackson and J. A. Lovegrove 1 - 5
It has been well documented that microbial metabolism of The mechanism of action of probiotics on cholesterol
bile acid is a peculiar probiotic effect involved in the reduction could include one or all of the above mechanisms,
therapeutic role of some bacteria. The deconjugation with an ability of different bacterial species to have varying
reaction is catalysed by a conjugated bile acid hydrolase effects on cholesterol lowering. Moreover, inconsistencies
enzyme, which is produced exclusively by bacteria. in the literature regarding beneficial effects of probiotics
Deconjugation is widely found in many intestinal bacteria could be due to a number of different factors. The period of
including genera such as Enterococcus, Peptostreptococcus, intervention, volume consumed and, more importantly, the
Bifidobacterium, Fusobacterium, Clostridium, Bacteroides bacterial titre of the product are all important considerations
and Lactobacillus (Hylemond 1985). This reaction liberates that may vary (Thompson et al. 1982; Richelsen et al.
an amino acid moiety and a deconjugated bile acid, thereby 1996). The baseline concentrations of cholesterol also affect
reducing cholesterol re-absorption by increasing faecal study outcomes, with hypercholesterolaemic groups
excretion of the deconjugated bile acids. Many in vitro responding to probiotics in some (Agerbaek et al. 1995;
studies have investigated the ability of various bacteria to Agerholm-Larsen et al. 2000a) but not all (Sessions et al.
deconjugate a variety of different bile acids. For example, 1997; De Roos et al. 1999) studies. The study outcome
Grill et al. (1995) reported Bifidobacterium longum as being depends also on the bacterial species used, its metabolic
the most efficient bacterium when tested against six capabilities, and viability throughout the gastrointestinal
different bile salts. Another study reported that tract (Jasper et al. 1984). Further research is required to
Lactobacillus species had varying abilities to deconjugate more fully elucidate the relative importance of such
glycocholate and taurocholate (Gilliland and Speck 1977). parameters before the true beneficial effects and mechanism
Studies performed on in vitro responses are useful, although of action of probiotics in relation to CHD can be
in vivo studies in animals and humans are required to more determined.
fully determine the contribution of bile acid deconjugation
to cholesterol reduction. Intervention studies on animals and 3. The effect of fructan-type oligosaccharide
ileostomy patients have shown that oral administration of prebiotics on lipid metabolism in humans
certain bacterial species can lead to an increased excretion
In recent years, there has been increasing interest in the
of free and secondary bile salts (De Smet et al. 1998;
important nutritional roles of prebiotics as functional food
Marteau et al. 1995).
ingredients. A prebiotic is a selectively metabolised dietary
There is also in vitro evidence to support the hypothesis
ingredient that stimulates 'beneficial' microorganisms in the
that some bacteria can assimilate (take up) cholesterol. It
lower gut. This interest has been derived from animal
has been reported that Lactobacillus acidophilus (Gilliland
studies which have shown marked reductions in TAGs and,
et al. 1985) and Bifidobacterium bifidum (Rasic et al. 1992)
to a lesser extent, cholesterol levels when diets containing
have the ability to assimilate cholesterol during in vitro
significant amounts of the prebiotic (oligofructose (OFS))
studies, but only in the presence of bile salts and under
were fed. However, studies conducted in humans examining
anaerobic conditions. However, despite such reports, there
the effects of prebiotics on plasma lipids levels have
is uncertainty about whether the bacteria are assimilating
generated inconsistent findings (Table 3). In individuals
cholesterol or whether cholesterol is co-precipitating with
with raised blood lipids, three studies have shown
the bile salts. Studies have been performed to address this
significant decreases in fasting total and LDL cholesterol,
question; for example, Klaver and Van der Meer (1993)
with no significant changes in TAG levels (Yamashita et al.
concluded that removal of cholesterol from the medium in
1984; Hidaka et al. 1991; Davidson et al. 1998), whereas
which Lactobacillus acidophilus and Bifidobacterium were
one recent study in type II diabetics did not reveal any
growing was not due to assimilation, but due to bacterial
change in cholesterol levels (Alles et al. 1999). In
bile salt deconjugase activity. The same question was
normolipidaemic subjects, only two studies involving
addressed by Tahri et al. (1995) but with conflicting results:
supplementation with inulin have demonstrated significant
they concluded that part of the removed cholesterol was
changes in both fasting TAG and total cholesterol levels
found in the cell extracts and that cholesterol assimilation
(Canzi et al. 1995; Brighenti et al. 1999), with another
and bile acid deconjugase activity could occur
study showing a significant decrease in TAG levels only
simultaneously.
(Causey et al. 2000). However, Luo et al. (1996) and
Cholesterol binding to bacterial cell walls has also been
Pedersen et al. (1997) have recently reported no effects of
suggested as a possible mechanism for the
OFS or inulin treatment on plasma lipid levels in young
hypocholesterolaemic effects of probiotics. Hosono and
healthy subjects. In a group of middle-aged men and
Tono-oka (1995) reported that Lactococcus lactis subsp.
women, lower plasma TAG levels were observed 8 wk after
lactis biovar. diacetylactis R-43 had the highest binding
inulin treatment compared to a placebo (Jackson et al.
capacity for cholesterol for a range of bacteria tested. It was
1999). In this study, follow-up blood samples were taken 4
speculated that differences in binding of the bacteria were
wk after completion of the supplementation period, by
due to chemical and structural properties of their cell walls,
which time concentrations of TAG had returned to baseline
and that even non-viable cells may have the ability to bind
values, thus supporting the conclusion that inulin feeding
cholesterol in the host intestinal tract.