lable at ScienceDirect

Nutrition 28 (2012) 733–736

Contents lists avai

Nutrition

journal homepage: www.nutr i t ionjrnl .com

Editorial

Do probiotics act more efficiently in foods than in supplements?

Probiotics history

It was the early 20th century when Mechnicoff extolled thevirtues of consuming fermented dairy products and postulatedhis “Longevity without aging” theory, in which he claimed thatlactic bacteria, by replacing the harmful bacteria indigenous to theintestines, prolong life. Tissier was another scientist who, almostat the same time, came upwith results convincing him that bifido-bacteria, the predominant component of breast-fed infants’ gutmicroflora, if replaced for the putrefactive bacteria, can relieve diar-rhea in non-breast-fed children. The history recording beneficialproperties of fermentedproducts,however, datesbackmanycentu-ries. Hippocrates prescribed yogurt to his patients to cure diarrheaand other intestinal disorders. Biblical scriptures have also docu-mented yogurt as a product for the treatment of some ailments [1].

Probiotic definition

Probiotics are defined as “live microorganisms which, whenadministered in adequate amounts, confer a health benefit onthe host” by the Food and Agriculture Organization (FAO)/WorldHealthOrganization [2]. Thisadequateamountvaries fromcountryto country; in Japan a product must contain a minimum of 107

colony forming units (CFU)/g of probiotic bacteria to be considereda probiotic one, whereas the USA has developed a standard thatrequires at least 108 CFU/g of the product to label it as probiotic[3]. However, generally a probiotic product should contain >106-108 CFU/g, or >108-1010 CFU/d of viable cells, which has beenshown to be efficacious, although there is no cell count leveldemonstrated to guarantee a health effect [2]. Some of the speciesused in probiotic products are 1) lactic acid–producing bacteria:lactobacillus, bifidobacterium, streptococcus; 2) non-lactic acid–producing bacterial species: bacillus, propionibacterium; 3) non-pathogenic yeasts: Saccharomyces; 4) non-spore-forming andnon-flagellated rod or coccobacilli [4].

A microorganism can be called probiotic if it fulfills thefollowing criteria: 1) the culture can be produced on an indus-trial scale; 2) the culture can survive during production andstorage; 3) the culture can tolerate the gut environment of thehost; and 4) the culture exerts health effects when consumed [5].

Documented health benefits of probiotics

Probiotics have been shown to be effective against a number ofdisorders. Some of themost documented effects are relieving diar-rhea, improving lactose intolerance, and its immunomodulatory,

0899-9007/$ - see front matter � 2012 Elsevier Inc. All rights reserved.doi:10.1016/j.nut.2012.01.012

anticarcinogenic, antidiabetic, hypocholesterolemic, and hypoten-sive properties [6–8].

Probiotic bacteria, by competing with enteric pathogens foravailable nutrients and binding sites, reducing the pH of thegut, producing a variety of chemicals that inactivate viruses,enhancing specific and non-specific immune responses andincreasing mucin production, can reduce the incidence, severity,and duration of diarrhea [9,10]. Alleviation of lactose intolerancesymptoms by probiotic bacteria is attributed to their intracellularb-galactosidase content [11]. Studies have revealed that probioticbacteria can induce many immunological changes and affectboth Th1 and Th2 cytokine production and that these effectsare strongly strain-specific [12].

Some major routes through which probiotic bacteria havebeen assumed to prevent cancer are binding to mutageniccompounds thus decreasing their absorption, suppression ofthe growth of bacteria that convert procarcinogens to carcino-gens, decreasing the activity of enzymes predictive of neoplasmincluding b-glucuronidase, nitroreductase, and choloylglycinehydrolase, as well as enhancing immune responses [13]. Inflam-mation plays a major role in both initiation and progression ofdiabetes [14,15]. By reducing inflammatory responses, probioticshave been shown to correct insulin sensitivity and reduce devel-opment of diabetes mellitus. This antiinflammatory effect hasbeen proposed to be rooted in immunomodulatory propertiesof probiotic bacteria [8]. By reducing cholesterol absorption inthe gut, incorporation of cholesterol into cell membranes, enzy-matically deconjugating bile salts, and conversion of cholesterolto coprostanol, probiotics can reduce blood cholesterol [8,16].Release of angiotensin-converting enzyme inhibitory peptidesfrom the parent protein through proteolytic action explainshow probiotics can exert antihypertensive effects [8].

In this study, all articles published between 2000 and 2011were searched in PubMed and Science Direct using probioticfood products and supplements as key words and only humanstudies were included. The efficacy of food products and supple-ments for transferring probiotics was reviewed in this study.

Probiotics in foods

Traditionally, yogurt was the first food to present consumerswith probiotics. Recently, the development of novel probioticfoods has attracted great attention and manufacturers arecoming out with new products including ice cream, cheese,chocolate, beverages, cereals, and vegetable products [17].

Editorial / Nutrition 28 (2012) 733–736734

Supplementationwith 1010 CFU of Lactobacillus casei in yogurtreduced the incidence of diarrhea [18]. Yogurt plus capsules con-taining a variety of probiotic bacteria including Lactobacillus bol-garicus, Streptococcus thermophilus, Bifidobacterium animalis, andBifidobacterium longum, when administered to lactose intoler-ants, increased fecal b-galactosidase activity and reducedsymptom scores [19]. Milk containing either 5 � 109 or 5 �1010 CFU of Bifidobacterium lactis increased CD4þ, CD25þ, naturalkiller cells, and phagocytic capacity of immune cells [20]. Anamount of 108-1010 CFU of L. casei in fermented milk onlyincreased oxidative burst capacity as well as natural killer cellstumoricidal activity [21]. Thirty-two weeks of interventionwith 6 � 109 CFU/mL of B. animalis in formula had no effect onfecal SIgA of non-breast-fed newborns [22]. Fermentedmilk con-taining Lactobacillus gasseri reduced IgE and increased Th1 cyto-kines in patients suffering perennial allergic rhinitis [23].Amounts of 3 � 108 CFU of Lactobacillus acidophilus and 27.9 �1010 CFU of B. lactis elevated the percentage of granolocytesand monocytes, showing phagocytic activity when administeredin yogurt to healthy subjects; however, oxidative burst activityand specific immune parameters remained unaffected [24].Formula containing 2.5 � 1010 CFU of Bifidobacterium bifidumand S. thermophilus increased CD4þ count in human immunode-ficiency virus–infected children [25]. Allergic children whenadministered 4 � 108 CFU of a combination of L. gasseri andLactobacillus corinyformis in yogurt showed decreased IgE inplasma and increased CD4þ, CD25þ, and natural killers [26]. Anamount of 1.95 � 1010 CFU of L. casei in milk left no effects onnatural killer cell activity in healthy men [27]. Extensively hydro-lyzed casein formula containing 3.4 � 109 CFU of L. rhamnosusGG decreased IgA- and IgM-secreting cells and increased propor-tions of CD19þ and CD27þ in infants with atopic dermatitis [28].Lactobacillus plantarum supplemented within powderedskimmed milk exerted different immune-enhancing effects inthe elderly subjects, depending on the dose [29].

Yogurt with a content of 4 � 106 CFU L. acidophilus and 3.6 �106 CFU of Bifidobacterium lactis reduced fasting blood glucose indiabetic patients [30]. Sausagewith 108 CFU of Lactobacillus para-casei had no significant effects on cholesterol fractions of healthysubjects, but decreased ICAM-1 expression on lymphocytes [31].B. longum when administered at a dose of 3 � 1010 CFU in milkwas capable of reducing total cholesterol only in those whohad mild hyperlipidemia [32]. Consumption of yogurt enrichedby 3 � 108 CFU of L. acidophilus and B. lactis for 6 weeks reducedtotal cholesterol significantly but had no effect on other types ofcholesterol [33]. Yogurt containing L. acidophilus and B. lactis ata dose of 4 � 106 CFU and 3.6 � 106 CFU, respectively, decreasedtotal and LDL cholesterol significantly but had no effect on HDLand triglycerides [34]. The very treatment also significantlydecreased total cholesterol: HDL cholesterol and LDL cholesterol,HDL cholesterol ratios, two major atherogenic indices [35]. Adrink called ProViva with 2 � 109 CFU of L. plantarum reducedsystolic blood pressure significantly [36] and tablets containingpowdered milk fermented with Lactobacillus helveticus reducedblood pressure as well [37].

Probiotics in supplements

Different forms of probiotic supplements are available in themarket including pills, capsules, tablets, gelcaps, liquids, andpowders [38].

An amount of 108 CFU of L. casei, when added to oral rehydra-tion solution in the form of powder, resulted in a shorter durationof diarrhea and a faster discharge from the hospital in children

[39]. Capsules containing 109 CFU of L. acidophilus and 109 CFUof Bifidobacterium infantis shortened the duration of diarrhea inchildren aswell [40]. Capsuleswith 4�1010 CFU of a combinationof Lactobacillus rhamnosus and Lactobacillus ruteri amelioratedacute diarrhea in children and shortened hospital stay [41].L. GG capsules at a dose of 109 CFU had no effect on severity orduration of diarrhea [42]. Five days of supplementation withcapsules containing 1.6 � 109 CFU of L. acidophilus, B. bifidum,and L. bolgaricus was just moderately effective in reducing diar-rhea duration in children [43]. Powder with a content of 1010

CFU L. paracasei led to a bettermanagement of non-rotavirus diar-rhea, butwas not effective in rotavirus type [44]. Children supple-mented with capsules containing 2.4 � 1010 CFU L. rhamnosusshowed reduced duration of diarrhea and time of intravenousrehydration [45]. Capsules containing 3�109 CFUof LactobacillusandB. infantis shortened thedurationof diarrheabuthadnoeffecton stool frequencyandhospitalization course [46]. A powder con-taining 12�107 CFUof L. GGhadno significant effect on frequencyor duration of diarrhea in children [47]. Either 2�1010 or 2�1012

CFUof L. GGdecreased the frequencyandduration of diarrhea andhospital stay [48]. A combination of 6�109 CFU L. acidophilus andB. bifidum administered in the form of powder to children couldshorten the duration of diarrhea, hospital stay, and stoolfrequency [49]. Children given powder containing 2.5 � 107

CFU/kg/d of Bifidobacterium mesentricus, Enterococcus faecalis,and Clostridium butyricum had less severe diarrhea and shorterhospital stay [50]. Capsules containing 15 � 109 CFU of L. GGhad no significant effect on the children suffering from diarrhea[51]. VSL3 capsules in either 4.5 � 1011 or 4 � 4.5 � 1011 CFUdose of four Lactobacillus and three Bifidobacteria strains hadno effect on lactose maldigestion parameters [52]. Lacidofilcapsules when administered to children with lactose intolerancereduced breath hydrogen significantly [53]. L. reuteri supple-mented in capsules also reduced breath hydrogen as well as clin-ical score in lactose-intolerant patients [54]. Three months ofsupplementationwith tablets containing 5�107 CFU of L. gasseri,B. longum, and B. bifidum enhanced cytotoxic plus T-suppressorcell and caused an even greater increase in T-helper cells [55].Capsules containing108,109,1010, or 1011 CFUofB. lactis and L. par-acasei had no effect on phagocytic activity in blood leukocytes,fecal IgA, or interferon-g, and IL-10 production [56]. Supplemen-tation with 19.5 � 109 CFU of L. casei restored neutrophil phago-cytic activity in cirrhosis, maybe through changing IL-10secretion and TLR4 expression [57]. A measure of 2 � 109 CFU ofBacillus coagulans in capsules increased TNF-a in response toadenovirus exposure and influenza A [58]. Powderwith a contentof B. mesentricus, E. faecalis, and C. butyricum, when administeredat a dose of 2.5 � 107 CFU/kg/d, increased IL-10 and down-regulated TNF-a [50]. An amount of 2 � 108 CFU of Lactobacillussalivarius induced natural killer cells and increased IgM, IgA,IgG, and IL-10 [59]. Capsules containing 109 CFU of L. plantarumand L. paracasei were effective in reducing the risk of acquiringcommon cold infections [60].

L. rhamnosus and Propionibacterium freudenreichii at a doseof2-5�1010 in capsules reducedexcretionof aflatoxinB-N, abiomarkerof cancer, in students residing in a Chinese province where expo-sure to aflatoxin is high [61]. Capsules containing 4 � 1010 CFU ofa combination of L. rhamnosus and P. freudenrechii decreasedactivity of b-glucosidase, an enzyme indicator of colon cancer risk[62]. No effects on colorectal cancer biomarkers were observedby B. lactis supplementation at a dose of 5 � 109 CFU [63]. Fourweeksof supplementationwith1010CFUofL. acidophiluspreservedinsulin sensitivity but had no effect on inflammatorymarkers [64].A measure of 6 � 1010 CFU of Lactobacillus aciphilus could reduce

Editorial / Nutrition 28 (2012) 733–736 735

cholesterol, but throughout the study, changes inserumlipidswereinsignificant [65]. Lactobacillus fermentum capsules at a dose of 4�109 had no significant effects on lipid profile either [66]. Capsulescontaining 4 � 1010 CFU of Lactobacillus rhamnosus and P. freuden-reichii did not affect blood lipids either [62].

Comparison

It seems hard to judgewhether foods or supplements act moreefficiently in exerting the claimed health effects, mainly becausethe results of different studies are strongly dependent on thestrain, dosage, period of intervention, and the condition studied.Unfortunately, thus far, to our knowledge, no studies have beenperformed comparing the efficacy of food versus supplements asthe probiotic carriers.

The efficacy of probiotic bacteria is mainly based on twofactors: viability (being live in food products and supplements)and survivability (sustaining their life through harsh conditions)as well as activity [55]. Several parameters including probioticstrain, pH of the matrix, nutritional component of the carrier,and heat treatment can affect viability and survivability [17,67–71]. Some techniques have been developed for increasing bacte-rial viability and survivability including preexposure to sublethalstresses such as salt, heat, bile, and lowpH, immobilized cell tech-nology, microencapsulation, genetic modification, combiningdifferent synergistic strains, and incorporation of nutrients andprebiotics to the matrix. Selection of the proper method dependson the type of product to be added the probiotic bacteria [69,72–75]. Factors affecting bacterial activity are water activity of thecarrier, access to essential nutrients for probiotic growth, pH ofthe matrix, and growth promoters [3].

Thus far, only one study that we know of has compared thesurvivability of probiotic bacteria in food versus supplements, inwhich fecal bacterial count was considered the indicator ofsurvivability. The results showed that matrix did not influencesurvival of lactobacilli strain but Bifidobacteria survived betterin yogurt [76]. However, the magnitude of health effects was notinvestigated and compared for different matrices in this study.

Conclusion

Returning to the hypothesis posted at the beginning of thisstudy, it is now possible to state that foods are better carriersfor probiotics than supplements. This article has given anaccount of thewidespread use of food products for the treatmentof several diseases in humans. The reason for this widespreadapplication of probiotic foods may be due to the buffering prop-erties of foods for probiotics during passage through the gut,provision of essential nutrients for maintaining the activity andefficacy of the probiotic bacteria, synergistic effects of food ingre-dients on probiotic growth, and consumer attitude toward probi-otic foods versus supplementation with tablets, capsules, andother drug forms [17,55,77].

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Aziz Homayoni Rad, Ph.D.a,*Elnaz Vaghef Mehrabany, M.Sc.b

Beitullah Alipoor, Ph.D.b

Leila Vaghef Mehrabany, M.Sc.b

Mina Javadi, B.Sc.baDepartment of Food Science and Technology

Faculty of Health and NutritionTabriz University of Medical Sciences

Tabriz, East Azarbaijan, Iran

bDepartment of Nutrition, Faculty of Health and NutritionTabriz University of Medical Sciences

Tabriz, East Azarbaijan, Iran�Corresponding author. Tel.: þ98 411 3357581;

fax: þ98 411 3340634.E-mail address: homayounia@tbzmed.ac.ir. (A. Homayoni Rad)