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An Extensively Hydrolyzed Formula Supplemented with Two Human Milk Oligosaccharides Modifies the Fecal Microbiome and Metabolome in Infants with Cow's Milk Protein Allergy.
Boulangé, CL, Pedersen, HK, Martin, FP, Siegwald, L, Pallejà Caro, A, Eklund, AC, Jia, W, Zhang, H, Berger, B, Sprenger, N, et al
International journal of molecular sciences. 2023;24(14)
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Human milk oligosaccharides (HMO) are important for the establishment and maturation of the early microbiome in infants and as such play a role in modulating immunity. The aim of this double-blind, randomised, controlled study was to evaluate the effect of HMO supplementation of extensively hydrolysed formula (EHF) on the faecal microbiome in infants with cow’s milk protein allergy (CMPA). 194 non-breastfed infants with CMPA were randomised to receive either an HMO supplemented EHF or control EHF until 12 months of age. The HMO supplemented infants displayed a higher abundance of bifidobacteria and slower microbiome maturation compared to controls as well as changes in faecal amino acid degradation and bile acid conjugation. These effects were more pronounced in infants who were started on the intervention before the age of 3 months. The authors concluded that HMO supplementation reversed, in part, the dysbiosis commonly observed in infants with CMPA.
Abstract
Cow's milk protein allergy (CMPA) is a prevalent food allergy among infants and young children. We conducted a randomized, multicenter intervention study involving 194 non-breastfed infants with CMPA until 12 months of age (clinical trial registration: NCT03085134). One exploratory objective was to assess the effects of a whey-based extensively hydrolyzed formula (EHF) supplemented with 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) on the fecal microbiome and metabolome in this population. Thus, fecal samples were collected at baseline, 1 and 3 months from enrollment, as well as at 12 months of age. Human milk oligosaccharides (HMO) supplementation led to the enrichment of bifidobacteria in the gut microbiome and delayed the shift of the microbiome composition toward an adult-like pattern. We identified specific HMO-mediated changes in fecal amino acid degradation and bile acid conjugation, particularly in infants commencing the HMO-supplemented formula before the age of three months. Thus, HMO supplementation partially corrected the dysbiosis commonly observed in infants with CMPA. Further investigation is necessary to determine the clinical significance of these findings in terms of a reduced incidence of respiratory infections and other potential health benefits.
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Effects of Fermented Milk Containing Lacticaseibacillus paracasei Strain Shirota on Constipation in Patients with Depression: A Randomized, Double-Blind, Placebo-Controlled Trial.
Zhang, X, Chen, S, Zhang, M, Ren, F, Ren, Y, Li, Y, Liu, N, Zhang, Y, Zhang, Q, Wang, R
Nutrients. 2021;13(7)
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Constipation is a common complaint among people with depression and may negatively affect their quality of life. In association with this, previous studies have shown a correlation between the reduction of Lactobacillus or Bifidobacterium strains in the gut of patients with major depressive disorder. Thus, this two-arm, parallel-design, randomised, double-blinded, placebo-controlled trial examined the effects of supplementing fermented milk with Lacticaseibacillus paracasei Strain Shirota or LcS (previously known as Lactobacillus casei strain Shirota) on constipation in people with depression. Symptoms of constipation, stool problems, and depressive symptoms improved after 9 weeks of consuming fermented milk containing LcS. The abundance of Adlercreutzia, Megasphaera, and Veillonella increased significantly in the intervention group. In contrast, the abundance of bacteria related to mental disorders such as Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter significantly decreased after the intervention. After 9 weeks of intervention with LcS, a significant reduction in serum proinflammatory cytokines such as IL-1β, IL-6, and TNF-α was observed in patients with depression. The intervention group also showed a decrease in inflammation-causing bacteria, Surrerella, which correlated with a reduction in proinflammatory cytokines. The mechanisms driving the changes in gut microbial composition, depression, and gastrointestinal symptoms after LcS intervention need to be evaluated in more robust studies. Healthcare professionals can use the results of the study to better understand how probiotics can reduce constipation and depression and improve gut microbial composition.
Abstract
Probiotics have been shown to benefit patients with constipation and depression, but whether they specifically alleviate constipation in patients with depression remains unclear. The aim of this study was to investigate the effect of Lacticaseibacillus paracasei strain Shirota (LcS), formerly Lactobacillus casei strain Shirota, on constipation in patients with depression with specific etiology and gut microbiota and on depressive regimens. Eighty-two patients with constipation were recruited. The subjects consumed 100 mL of a LcS beverage (108 CFU/mL) or placebo every day for 9 weeks. After ingesting beverages for this period, we observed no significant differences in the total patient constipation-symptom (PAC-SYM) scores in the LcS group when compared with the placebo group. However, symptoms/scores in item 7 (rectal tearing or bleeding after a bowel movement) and items 8-12 (stool symptom subscale) were more alleviated in the LcS group than in the placebo group. The Beck Depression Index (BDI) and Hamilton Depression Rating Scale (HAMD) scores were all significantly decreased, and the degree of depression was significantly improved in both the placebo and LcS groups (p < 0.05), but there was no significant difference between the groups. The LcS intervention increased the beneficial Adlercreutzia, Megasphaera and Veillonella levels and decreased the bacterial levels related to mental illness, such as Rikenellaceae_RC9_gut_group, Sutterella and Oscillibacter. Additionally, the interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) levels were significantly decreased in both the placebo and LcS groups (p < 0.05). In particular, the IL-6 levels were significantly lower in the LcS group than the placebo group after the ingestion period (p < 0.05). In conclusion, the daily consumption of LcS for 9 weeks appeared to relieve constipation and improve the potentially depressive symptoms in patients with depression and significantly decrease the IL-6 levels. In addition, the LcS supplementation also appeared to regulate the intestinal microbiota related to mental illness.
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Efficacy of probiotics on digestive disorders and acute respiratory infections: a controlled clinical trial in young Vietnamese children.
Mai, TT, Thi Thu, P, Thi Hang, H, Trang, TTT, Yui, S, Shigehisa, A, Tien, VT, Dung, TV, Nga, PB, Hung, NT, et al
European journal of clinical nutrition. 2021;75(3):513-520
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The World Health Organization (WHO) reported that acute respiratory infection (ARI) is the leading cause of death in children followed by diarrhoea and constipation. In Vietnam, despite many achievements in malnutrition prevention, the rate of malnutrition is elevated. Malnutrition results in ARI, diarrhoea, and physical and mental retardation in children The aim of this study was to investigate the effects of a probiotic fermented milk product containing Lactobacillus casei strain Shirota (LcS) on gastrointestinal symptoms, respiratory infections, and the nutrition status of children from Vietnam. This study was a community based, controlled open trial and it was conducted over a period of 18 weeks consisting of 2-week screening/pre-observational period; 12-week intervention period; and 4-week postintervention period. A total of 1036 children (518 children in the Control group and 518 children in the Probiotic group) were enrolled in this study. Results showed a significant reduction in the incidence of constipation and beneficial effects to prevent infectious diseases in Vietnamese children. Furthermore, while LcS did not affect the duration of diarrhoea, the incidence of diarrhoea tended to be improved after 12 weeks of intervention. Authors conclude that habitual consumption of fermented milk containing LcS prevented constipation and ARI in Vietnamese children, and it may be useful for treating diarrhoea and improving nutritional status, thus conferring remarkable health benefits to children in Vietnam.
Abstract
OBJECTIVES To evaluate the efficacy of fermented milk containing Lactobacillus casei strain Shirota (LcS) on the incidence of constipation, diarrhea, acute respiratory infections (ARI), and nutritional status of young Vietnamese children. METHODS A controlled field trial was conducted with 1003 children (3-5 years old) in Thanh Hoa province in Vietnam. The probiotic group (n = 510) consumed fermented milk 65 mL/day containing 108 CFU/mL of LcS for the 12-week intervention period, whereas the control group (n = 493) was not given any. The incidence of constipation, diarrhea, ARI, and anthropometry in children was determined at baseline, after 4, 8, and 12-week intervention, and after the 4-week follow-up period. RESULTS Probiotic drink decreased the incidence of constipation after the 12-week intervention period (12.0% vs. 32.0%, OR = 0.28 (95% CI: 0.21-0.40), p < 0.001), tended to decrease the incidence of diarrhea (4.9% vs. 7.9%, OR = 0.60 (95% CI: 0.35-1.01), p = 0.068), and prevented the occurrence of ARI (15.9% vs. 24.5%, OR = 0.58 (95% CI: 0.42-0.79), p < 0.001), when compared with the control group. In contrast, no probiotic effects were observed for the duration of diarrhea or ARI. Weight gain was higher in the probiotic group than in the control group after 4, 8, and 12-week intervention and after the 4-week follow-up period (p < 0.05). CONCLUSIONS Daily intake of fermented milk containing LcS strongly prevented the incidence of constipation and ARI in Vietnamese children. This study also revealed the potential effects of the use of a probiotic drink on diarrhea prevention as well as nutritional status improvement.
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Bioactivity of soy-based fermented foods: A review.
Cao, ZH, Green-Johnson, JM, Buckley, ND, Lin, QY
Biotechnology advances. 2019;37(1):223-238
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Fermented foods are growing in popularity in the West due to their unique flavour and nutritional value. This review investigates the fermentation processes, health-associated bioactive components and underlying mechanisms of the popular fermented soy products Natto, fermented soy milk, Tempeh and soy sauce. Each fermented soy product is summarised based on functional activities. The existing literature points to an overall positive effect on bone health and immune activities. Interestingly, each fermented soy food exhibits different profiles of bioactive components and therefore different mechanisms of action. Based on this review, the authors conclude there is a need for further in-depth human studies with large sample sizes and long-term follow up to better understand these foods benefits and potential toxicity.
Abstract
For centuries, fermented soy foods have been dietary staples in Asia and, now, in response to consumer demand, they are available throughout the world. Fermentation bestows unique flavors, boosts nutritional values and increases or adds new functional properties. In this review, we describe the functional properties and underlying action mechanisms of soy-based fermented foods such as Natto, fermented soy milk, Tempeh and soy sauce. When possible, the contribution of specific bioactive components is highlighted. While numerous studies with in vitro and animal models have hinted at the functionality of fermented soy foods, ascribing health benefits requires well-designed, often complex human studies with analysis of diet, lifestyle, family and medical history combined with long-term follow-ups for each subject. In addition, the contribution of the microbiome to the bioactivities of fermented soy foods, possibly mediated through direct action or bioactive metabolites, needs to be studied. Potential synergy or other interactions among the microorganisms carrying out the fermentation and the host's microbial community may also contribute to food functionality, but the details still require elucidation. Finally, safety evaluation of fermented soy foods has been limited, but is essential in order to provide guidelines for consumption and confirm lack of toxicity.
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Is perceived intolerance to milk and wheat associated with the corresponding IgG and IgA food antibodies? A cross sectional study in subjects with morbid obesity and gastrointestinal symptoms.
Kvehaugen, AS, Tveiten, D, Farup, PG
BMC gastroenterology. 2018;18(1):22
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Dairy and gluten are the most common triggers of irritable bowel syndrome (IBS) in the general population. Food intolerance is generally detected by IgG antibodies, but the test is controversial. In this cross-sectional study, 97 obese subjects (82.4% women) were included, of which 72.1% had gastrointestinal symptoms, 35.7% had IBS, 31.4% had symptoms of milk intolerance, 28.6% had symptoms of wheat intolerance, and 15.7% had symptoms of intolerance to both milk and wheat. The study examined the association between IgA and IgG antibodies corresponding to milk and wheat in subjects with and without gastrointestinal issues and with and without perceptions of food sensitivity. The results of this study found no association between s-IgG and s-IgA antibodies and perceived food intolerances to milk and wheat among morbidly obese subjects. Although IgA against gliadin correlated with increased levels of zonulin, a marker of intestinal permeability, tight-junctional gut permeability inversely correlated with wheat intolerance. Furthermore, the study results revealed a significant correlation between hypothyroidism and IgG against wheat and a marginal correlation between hypothyroidism and IgG against gluten. Further robust research is needed to confirm these findings. Healthcare professionals can use the results of this study to understand the current developments and the controversy surrounding food intolerance testing.
Abstract
BACKGROUND Serum IgG and IgA food antibodies have been used for dietary advice to subjects with gastrointestinal symptoms and perceived food intolerance, but the role of these antibodies in mediating intolerance is controversial. The present study investigated associations between perceived gastrointestinal intolerance to milk-or wheat and the corresponding s-IgG and s-IgA food antibodies in subjects with morbid obesity. METHODS Subjects with morbid obesity (BMI ≥ 40 kg/m2 or ≥35 kg/m2 with obesity-related complications) were included. Irritable Bowel Syndrome (IBS) was diagnosed based on the Rome III criteria. Severity of specific gastrointestinal symptoms were measured with the Gastrointestinal Symptom Rating Scale (GSRS)-IBS. S-IgG against cow's milk, cheese, wheat and gluten, and s-IgA against casein and gliadin were measured. RESULTS Ninety-seven subjects (80 females) with mean age 45 (SD 8.4) years were included, 70 had gastrointestinal complaints, 25 had IBS, and 22 and 20 reported milk- and wheat- intolerance respectively. There were no significant differences in serum concentrations or proportions of subjects above defined cut-off values for the antibodies between subjects with and without gastrointestinal complaints. In the group with gastrointestinal complaints, no significant differences were found between subjects with and without perceived food intolerance. Except for a significant correlation between IgG against cheese and GSRS-diarrhea (Rho: -0.25, P = 0.04), no significant correlations were found between the antibodies and type or degree of gastrointestinal symptoms, including IBS. CONCLUSIONS The study showed no associations between perceived milk or wheat intolerance and the corresponding s-IgG and s-IgA food antibodies in subjects with morbid obesity.
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Beverage consumption patterns among 4-19 y old children in 2009-14 NHANES show that the milk and 100% juice pattern is associated with better diets.
Maillot, M, Rehm, CD, Vieux, F, Rose, CM, Drewnowski, A
Nutrition journal. 2018;17(1):54
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Recommendations for milk and/or fruit juice consumption in children’s diets has remained inconclusive. The aim of this study was to assess whether patterns in beverage consumption among children and adolescents can influence food choices and overall diet quality. Beverage consumption patterns of 8119 children and adolescents were analysed based on data from the National Health and Nutrition Examination Survey (NHANES). Beverage patterns were defined as milk pattern, juice pattern, milk and juice or other caloric beverages. This analysis found that while children rarely limit their drinking choices to a single beverage, those who primarily consumed milk, juice or a combination of the two were associated with better dietary choices. Based on this study, the authors conclude that promotion of milk and juice consumption, compared to other caloric beverages, may be an effective way to improve overall diet quality in children and adolescents.
Abstract
BACKGROUND Patterns of beverage consumption among children and adolescents can be indicative of food choices and total diet quality. METHODS Analyses of beverage consumption patterns among 8119 children aged 4-19 y were based on the first 24-h recall of the National Health and Nutrition Examination Survey (2009-14 NHANES). Four pre-defined beverage patterns were: 1) milk pattern; 2) 100% juice pattern; 3) milk and 100% juice pattern; and 4) other caloric beverages. Food- and nutrient-based diet quality measures included the Healthy Eating Index 2010. RESULTS Most children drank other caloric beverages, as opposed to milk (17.8%), 100% juice (5.6%), or milk and 100% juice (13.5%). Drinkers of milk and 100% juice had diets that did not differ from each other in total calories, total and added sugars, fiber, or vitamin E. Milk drinkers consumed more dairy and had higher intakes of calcium, potassium, vitamin A and vitamin D as compared to all other patterns. Juice drinkers consumed more total fruit, same amounts of whole fruit, and had higher intakes of vitamin C as compared to the other consumption patterns. Drinkers of both milk and 100% juice had the highest HEI 2010 scores of all the consumption patterns. CONCLUSIONS Beverage consumption patterns built around milk and/or 100% juice were relatively uncommon. Promoting the drinking of milk and 100% juice, in preference to other caloric beverages, may be an effective strategy to improve children's diet quality. Restricting milk and 100% juice consumption may encourage the selection of other caloric beverages.
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Self-reported bovine milk intake is associated with oral microbiota composition.
Johansson, I, Esberg, A, Eriksson, L, Haworth, S, Lif Holgerson, P
PloS one. 2018;13(3):e0193504
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Dietary bovine milk consumption has been associated with both positive and negative health effects. The aim of this study was to explore the association between bovine milk intake and oral microbiota profile. Saliva and tooth biofilm samples were obtained from 154 Swedish adolescents and food frequency questionnaires were completed. A replication cohort of 31,571 was also studied to find patterns in diet intake, lifestyle factors and dental caries. The primary finding of this study was that bovine milk consumption can modulate oral microbiota, and that low milk intake was associated with higher prevalence of opportunistic bacteria. Interestingly there was no association between milk intake and dental caries, highlighting the complexity of this disease. Based on these results, the authors hypothesise milk consumption may also produce similar effects in the gut microbiome.
Abstract
Bovine milk intake has been associated with various disease outcomes, with modulation of the gastro-intestinal microbiome being suggested as one potential mechanism. The aim of the present study was to explore the oral microbiota in relation to variation in self-reported milk intake. Saliva and tooth biofilm microbiota was characterized by 16S rDNA sequencing, PCR and cultivation in 154 Swedish adolescents, and information on diet and other lifestyle markers were obtained from a questionnaire, and dental caries from clinical examination. A replication cohort of 31,571 adults with similar information on diet intake, other lifestyle markers and caries was also studied. Multivariate partial least squares (PLS) modelling separated adolescents with low milk intake (lowest tertile with <0.4 servings/day) apart from those with high intake of milk (≥3.7 servings/day) based on saliva and tooth biofilm, respectively. Taxa in several genera contributed to this separation, and milk intake was inversely associated with the caries causing Streptococcus mutans in saliva and tooth biofilm samples by sequencing, PCR and cultivation. Despite the difference in S. mutans colonization, caries prevalence did not differ between milk consumption groups in the adolescents or the adults in the replication cohort, which may reflect that a significant positive association between intake of milk and sweet products was present in both the study and replication group. It was concluded that high milk intake correlates with different oral microbiota and it is hypothesized that milk may confer similar effects in the gut. The study also illustrated that reduction of one single disease associated bacterial species, such as S. mutans by milk intake, may modulate but not prevent development of complex diseases, such as caries, due to adverse effects from other causal factors, such as sugar intake in the present study.
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Fecal Microbiome and Food Allergy in Pediatric Atopic Dermatitis: A Cross-Sectional Pilot Study.
Fieten, KB, Totté, JEE, Levin, E, Reyman, M, Meijer, Y, Knulst, A, Schuren, F, Pasmans, SGMA
International archives of allergy and immunology. 2018;175(1-2):77-84
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Atopic diseases, such as atopic dermatitis (AD), asthma and rhinitis, are on the increase worldwide. Exposure to microbes may be important in the development of an atopic disease. Specifically, reduced early-life exposure is thought to be a contributing factor because microbial colonisation of the intestines during infancy plays a crucial role in the maturation of the immune system. AD, also called eczema, is an inflammatory skin disease often seen in small children. Food allergies are common in children with AD, the most common allergens being eggs, cow’s milk, peanuts, soy and wheat. This cross-sectional observational pilot study with 82 young children with a diagnosis of AD set out to identify distinct microbial patterns in the children’s faecal microbiomes associated with a clinical diagnosis of food allergy. Stool and blood samples were collected for a microbiome analysis and IgE antibody measurement, respectively. 20 children had a confirmed food allergy (most commonly to cow’s milk and peanuts), while almost half of the children without a diagnosed food allergy were sensitised to common food allergens after a food challenge. The study identified a faecal microbial signature in children with AD that differentiates between the presence and absence of food allergy. Children with AD and food allergy had more Escherichia coli and Bifidobacterium pseudocatenulatum species and less Bifidobacterium breve, Faecalibacterium prausnitzii and Akkermansia muciniphila species than children without food allergy. The authors concluded that the study supports a hypothesis that the intestinal microbiome differs in children with AD, depending on whether they have a food allergy or not. They call for future studies to confirm these findings.
Abstract
BACKGROUND Exposure to microbes may be important in the development of atopic disease. Atopic diseases have been associated with specific characteristics of the intestinal microbiome. The link between intestinal microbiota and food allergy has rarely been studied, and the gold standard for diagnosing food allergy (double-blind placebo-controlled food challenge [DBPCFC]) has seldom been used. We aimed to distinguish fecal microbial signatures for food allergy in children with atopic dermatitis (AD). METHODS Pediatric patients with AD, with and without food allergy, were included in this cross-sectional observational pilot study. AD was diagnosed according to the UK Working Party criteria. Food allergy was defined as a positive DBPCFC or a convincing clinical history, in combination with sensitization to the relevant food allergen. Fecal samples were analyzed using 16S rRNA microbial analysis. Microbial signature species, discriminating between the presence and absence food allergy, were selected by elastic net regression. RESULTS Eighty-two children with AD (39 girls) with a median age of 2.5 years, and 20 of whom were diagnosed with food allergy, provided fecal samples. Food allergy to peanut and cow's milk was the most common. Six bacterial species from the fecal microbiome were identified, that, when combined, distinguished between children with and without food allergy: Bifidobacterium breve, Bifidobacterium pseudocatenulatum, Bifidobacterium adolescentis, Escherichia coli, Faecalibacterium prausnitzii, and Akkermansia muciniphila (AUC 0.83, sensitivity 0.77, specificity 0.80). CONCLUSIONS In this pilot study, we identified a microbial signature in children with AD that discriminates between the absence and presence of food allergy. Future studies are needed to confirm our findings.
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Dairy intake revisited - associations between dairy intake and lifestyle related cardio-metabolic risk factors in a high milk consuming population.
Johansson, I, Nilsson, LM, Esberg, A, Jansson, JH, Winkvist, A
Nutrition journal. 2018;17(1):110
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Dairy intake and mortality has been evaluated in many studies but the results have been inconclusive. The aim of this cross-sectional and longitudinal study was to evaluate the association between different types of dairy products and metabolic risk markers for cardiovascular disease. Utilising data from the Swedish Vasterbotten Intervention Programme, 90,512 participants completed a food frequency questionnaire and had metabolic risk markers measured for the cross-sectional component of this study. From this cohort, 27,682 subjects returned within 8-11 years to complete the longitudinal component. Dairy intake was further classified as non-fermented milk, fermented milk, cheese and butter. Based on this cross-sectional and longitudinal data, the likelihood of having an undesirable body mass index (BMI) decreased with increasing amount of total dairy, cheese and butter intake, but increased with increasing non-fermented milk intake. According to these results, the authors conclude confounding variables are likely influencing the association between dairy intake and metabolic disease and suggest future studies be stratified by dairy type.
Abstract
BACKGROUND The association between milk and dairy intake and the incidence of cardiometabolic diseases, cancer and mortality has been evaluated in many studies, but these studies have had conflicting results with no clear conclusion on causal or confounding associations. The present study aims to further address this association by cross-sectional and longitudinal evaluation of the associations between exposure to various types of dairy products and metabolic risk markers among inhabitants in northern Sweden while taking other lifestyle factors into account. METHODS Respondents in the Västerbotten Intervention Programme with complete and plausible diet data between 1991 and 2016 were included, yielding 124,934 observations from 90,512 unique subjects. For longitudinal analysis, 27,682 participants with a visit 8-12 years after the first visit were identified. All participants completed a validated Food Frequency Questionnaire. Metabolic risk markers, including body mass index (BMI), blood pressure, serum (S) cholesterol and triglycerides, and blood glucose, were measured. Participants were categorized into quintiles by intake of dairy products, and risk (odds ratios, OR) of undesirable levels of metabolic risk markers was assessed in multivariable logistic regression analyses. In longitudinal analyses, intake quintiles were related to desirable levels of metabolic risk markers at both visits or deterioration at follow-up using Cox regression analyses. RESULTS The OR of being classified with an undesirable BMI decreased with increasing quintiles of total dairy, cheese and butter intake but increased with increasing non-fermented milk intake. The OR of being classified with an undesirable S-cholesterol level increased with increasing intake of total dairy, butter and high fat (3%) non-fermented milk, whereas an undesirable S-triglyceride level was inversely associated with cheese and butter intake in women. In longitudinal analyses, increasing butter intake was associated with deterioration of S-cholesterol and blood glucose levels, whereas increasing cheese intake was associated with a lower risk of deterioration of S-triglycerides. CONCLUSIONS Confounding factors likely contribute to the demonstrated association between dairy intake and mortality, and other medical conditions and analyses should be stratified by dairy type.