Milk intake and risk of mortality and fractures in women and men: cohort studiesBMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g6015 (Published 28 October 2014) Cite this as: BMJ 2014;349:g6015
All rapid responses
Consumers get to read just about everything and the contrary regarding the benefits or harmful effects of milk on health. There is an urgent need for clarification.
Let us look at this from consumers’ vantage point. You get to hear and read just about everything and the contrary about milk. The simple fact that the same word can be used for something man-made that has never come out of any mammal’s udder (rice milk, almond milk, soy milk…) is baffling in itself, and adds to the confusion. This latest scientific article deals with hip fracture risk and mortality among milk drinkers and cheese eaters. Data does not provide any definite answer. Still, it is possible to draw a few common sense tips from it, based on evidence.
It was an observational study: the research team monitored two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997). They were submitted food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997. Their health status was assessed using health insurance data, in order to know if they suffered from a hip fracture or if they died. This method makes the study very reliable in terms of following up on the patients.
Here are the results:
High milk intake (3 glasses of milk a day or more) was associated with higher cardiovascular and cancer mortality, as well as and with higher fracture incidence in one cohort of women. With male participants, we observed a higher cardiovascular mortality. The risk is limited among men but significant among women.
Why is a cautious interpretation of the results recommended? Well, here we see correlation and not causality. This is not an interventional study and we did not ask a group of people who did not consume milk to start consuming it. Given the observational study design, there is the inherent possibility of residual confounding and reverse causation phenomena.
Let us also note that fermented dairy products consumption was not linked to higher mortality or fracture incidence.
The research team offers several hypotheses to explain the correlation between higher consumption of milk and higher hip fracture and morality. What can we take out of it?
1. “Milk = Calcium = Bone health” is simplistic and most likely erroneous, if we do not account for other factors. This is not news, since milk does not help fighting osteoporosis nor heal fractures (Feskanich D, Willet WC, Stampfer MJ, Colditz GA. Milk, dietary calcium, and bone fractures in women: a 12-year prospective study. Am J Public Health 1997;87:992-7). Bone’s complex structure is more relevant to its health than calcium actually is. If the bone structure is deficient, calcium will not properly be integrated and the bone will break easily. The structure is made out of proteins (50% of bone volume, 1/3 of its mass) and it gets stronger with exercise and vitamin D production due to exposition to the sun. Our indoor, sedentary lifestyle is what weakens the bone. Therefore we need to use our muscles as they pull on the bone, which is what induces bone strengthening. We also need to go out in the sun in order to activate vitamin D production, or take food supplement in the winter to make up for the lack of sun. Those are the prime factors to consider before calcium.
2. Throughout the evolution of the human species, we swapped plants and vegetables for cereals. They contain but little calcium and can promote decalcification because of phytic acid. We ought to avoid calcium supplements, as they increase cardiovascular mortality, at least among men. Therefore milk is really useful for nutrient intake. It should not be the sole calcium intake though, and vegetables are both accessible and affordable, provided we select those in season. We ought to increase the quantity of fruits and vegetables at the expense of processed foods, mostly those derived from wheat (pastries, cake, industrial bread, pasta etc.) for a varied calcium intake. In vegetable leafs (salad, spinach, Swiss chard, parsley, algae) calcium is highly absorbable.
3. Which nutrients other than calcium are essential for the bone? Well, there are at least two.
First of all, proteins: dairy products are a prime source, vegetable proteins, meat and fish. The protein intake among seniors is insufficient.
Then long-chain omega-3 acids: they are synthesized by fatty fish for the most part. The amount in our body really depends on diet and is correlated with a decreased risk of hip fracture among women. Sardines, mackerel, tuna and anchovies are excellent sources of long-chain omega-3 acids.
4. According to this Swedish study and other research, it seems very likely that milk is less adapted to our adult needs than cheese, especially pressed cheese. Why? Several hypotheses are discussed by the authors. In particular, there is one about lactose, the sugar in milk being made of a molecule of glucose and one of galactose (sugar was discovered by Pasteur in 1856). But galactose induces a form of oxidative stress and glucose, hyperglycemia similar to what happens in the body after fruit juice absorption. Oxidative stress and hyperglycemia promote chronic inflammation, which leads to cardiovascular diseases and bone fragility. Hard, pressed, ripened cheese contains less glucose, since it is used by bacteria for fermentation, and a bit less galactose. Some cheeses contain just traces of them. This could explain such a big gap in effects: milk and non-fermented dairy products can have deleterious effects on adults, but are necessary to new-born and children, while other cheeses are neutral. Study authors showed chronic inflammation among milk drinkers, in proportion to their consumption.
5. In view of the stakes, the controversies on milk being “a poison” or “cancer inducing” are senseless. They promote food scares, which are a way to pursue business to some food brands. It is also noteworthy that we consume much less milk than people from Northern countries do. However, when it comes to food recommendations, “one size fits all” simply doesn’t apply. Current nutritional recommendations are just too similar. Some digest lactose very poorly (most notably Asians and Africans), other will digest sheep or goat milk much easier.
These natural adjustments are often made by the consumer himself, since enzymatic resources are linked to our own genomics. Some more difficult cases can be managed by an allergist.
But ultimately, pressed, ripened cheeses are well digested and preferred to milk consumption among adults. Beyond the milk / cheese duality, the dairy products industry has seen its offer evolve a lot these last few years and many more products derived from milk are now available. These industrial dairy products are often made out of little or not-fermented milk, or even skimmed milk. In that sense, they are included in the amount of milk consumed. Furthermore, they are almost always sweetened, which our metabolism can hardly handle anymore. It is best to avoid them since there are already so many sources of sugar (simple sugars, starch of all sorts).
Lastly, this study shows no evidence that fat-free is any better. Quite the opposite in fact: cheeses not correlated with increased mortality are, for the vast majority, made with whole milk. Nothing in this study could tell us to avoid fats from milk or cheese.
Competing interests: No competing interests
Not only do Helen M Macdonald, Alexandra Mavroeidi and Alison Avenell dislike our results in general, they furthermore criticize our findings as not based on sound science from mainly three aspects: misclassification of milk intake by a food frequency questionnaire, residual confounding and the fact that galactose is existent in fermented dairy products.
We fully agree that an accurate dietary assessment is difficult to accomplish. In our cohort studies, we used comprehensive food frequency questionnaires. These questionnaires have been validated as described in our Methods. According to these validation studies of milk intake, the correlation between the FFQ and four gold standard reference weighed 7-day food records every third month have been approximately 0.7 (1). Further, in both women and men we have previously found a positive association between reported intake of milk and the fat tissue content of pentadecanoic acid, a biologic marker reflecting average long-term dairy fat intake (2, 3). Nevertheless, the consequence of non-differential misclassification when measuring dietary intake in cohort studies can partially be compensated by an increase in study size and in number of outcomes, and additionally by repeat dietary assessments (4) - as was the case in our female cohort study. Indeed, the associations were stronger among women where we used time-dependent exposure analysis taking advantage of the repeat FFQs and where the analysis was based on a larger number of outcomes compared with the male cohort analysis (5), and also compared with previous fracture analysis of the female cohort (6). Non-differential misclassification of the exposure normally leads to conservatively biased estimates.
The possibility of residual confounding has been well acknowledged by us in the article (5). Helen M Macdonald et al seem, however, not to have carefully read our text where it is clearly described that we did take into account fat intake, including saturated fat intake, and retinol in our analyses (p 3, Statistical analysis, and p 4, Sensitivity analysis). Our estimates were not attenuated by these adjustments (Supplementary table E). Coffee intake was related to a somewhat higher risk of fracture in one previous analysis (7) but not in later more extensive analyses, neither in women (8) nor in men (9). Moreover, coffee intake has in recent large observational studies (10-12) been suggested to lower the rate of mortality, not the opposite. Nonetheless, with the addition of coffee intake to our multivariable model and with <1 glass of milk per day as the reference, the HRs of hip fracture for the higher categories were 1.19 (95% CI 188.8.131.52; 1 to <2 glasses/day), 1.54 (95% CI 1.41-1.68; 2 to <3 glasses/day), and 1.58 (95% CI 1.37-1.82; ≥3 glasses/day). Similarly and expectedly, our estimates for mortality were only marginally affected after adjustment for coffee intake.
Finally, we have never claimed that soured milk and yogurt are free of galactose. What we in the Introduction stated was: “Separating milk intake from the consumption of other dairy products may be of importance since a less pronounced induction of oxidative stress and inflammation in humans is expected with cheese and fermented dairy products (for example, soured milk and yogurt) because of their lower or non-existent lactose and galactose content,14 15 possible probiotic antioxidant and anti-inflammatory effects,16 17 18 and effects on gut microbiota.19 20 21 Indeed, a high intake of fermented milk products has been associated with a decreased risk of cardiovascular diseases,18 22 23 24 whereas a high milk intake is related to a tendency of an unfavourable risk profile for the development of diabetes and cardiovascular disease.18 23 24”
Detailed analysis of our article’s reference 14 (by Livia Alm), an old but highly relevant reference regarding lactose and galactose in Swedish dairy products, revealed 10-50% lower galactose content in different fermented milk products compared with non-fermented milk. By use of more contemporary analytical techniques, there is an ongoing examination at the Swedish University of Agricultural Sciences of the sugar components in present Swedish liquid dairy products. Hard cheeses are nowadays recommended for people with galactosaemia since they have undetectable levels of galactose (13). Given these facts and our hypothesis, it is for us surprising to find a suggestion from Macdonald et al that all milk products should in an etiologic analysis have been analyzed together. In an effort to gain further knowledge, such an approach would not be recommended from a scientific point of view.
Arne Astrup and Ian Givens have made a rhetorically elegant attempt to criticize our publication. Had they, however, read our article carefully, including our supplementary material, our previous responses to commentaries and their own references they would have saved words and time.
They begin by citing some recent meta-analyses concluding a null association between milk intake and all-cause mortality as well as cardiovascular mortality. One problem, if you carefully scrutinize the original studies, is that several of them have not separated non-fermented from fermented milk intake in the exposure assessment, with the risk of mixing apples and oranges. There are also formally tested heterogeneities in the study results with some studies displaying a tendency of lower and some tendency towards higher mortality rates with increasing reported consumption of milk, which is an indication of methodological differences in study designs and analyses. Indeed, meta-analysis of published data from dietary studies is problematic because of the wide variety of ways that data have been analyzed and presented. Valid dose-response examinations in meta-analyses are also difficult to accomplish without individual data. The use of pooled analyses based on primary data is a more attractive methodology that allows a coherent analytic approach in included studies (14). Let us remind the reader of the fact that our female cohort included a large number of outcomes compared with earlier studies, that we have specific analysis of different dairy products, a wide exposure range and have applied time-dependent exposure analysis – all highly relevant when interpreting the study findings. We are fully aware that an accurate dietary assessment is difficult to accomplish in large scale studies, as also discussed above. However, the total error in the exposure assessment can be reduced by repeated examinations and by a larger study size, which improves the possibility to detect not only an association but also to determine the strength of the association. Meta-analysis of smaller studies will only render higher precision of the composite estimate and will not modify the magnitude of the estimate.
We note with interest the claim that osteoporosis is a paediatric disease with geriatric consequences. This claim is of especial interest given the recent study results by Feskanich et al based on the Nurses' Health Study and the Health Professionals Follow-up Study in the United States, displaying higher – not lower - risk of hip fracture in men with a high teenage consumption of milk and a null finding in women (15). Arne Astrup and Ian Givens forgot to mention these recent results.
Furthermore, in support of their view that high milk consumption will reduce fragility fractures Astrup and Givens mention the study by Sahni et al (16). This cohort analysis, based on a single FFQ, included 764 (not 830) men and women with an age range between 68 and 96 years. During the 12 year follow-up, a total of 97 hip fracture cases were identified. These hip fractures were self-reported, which is of potential importance for the interpretation of the study results since some fractures might not have been identified, especially since there are high mortality rates in the first months after the hip fracture event (17). No associations between dairy intake (milk or other products) were found when the exposures were examined as continuous variables. No spline curves are presented. The tendencies of statistically significant results from the categorical analyses emerged based on different categorizations depending on type of dairy analyzed. Choosing a reference category (e.g., 1 serving/week or less of milk) with the lowest number of outcomes and participants is not a recommended epidemiological approach. Only multivariable adjusted results are presented, which is also not recommended by the STROBE guidelines (18), but the attempts for adjustment did not include comorbid conditions. Moreover, the change in estimate approach is nowadays not recommended for covariate selection (4). Given these facts, it seems somewhat remarkable that Arne Astrup and Ian Givens consider the Framingham study to offer good scientific support for the notion that greater intakes of milk lower the risk for hip fractures in older adults.
Regarding biomarkers, milk intake estimated by our FFQ has been validated against the fat tissue content of pentadecanoic acid, a biologic marker reflecting average long-term milk fat intake, i.e., existent in both milk and fermented milk products (2, 3). Such biomarkers cannot distinguish between effects on health from non-fermented and fermented milk products.
We disagree with the authors’ opinion regarding our study as an outlier. As already explained in regard to the previous meta-analytical approaches made, these results stem from heterogenetic study results with some individual studies displaying tendencies of higher risk of mortality and fracture with high milk consumption while other researchers find associations in the opposite direction. Although we can’t rule out the possibility of biased results with the four observational study designs included in our article, a more likely explanation for our more obvious study findings compared with earlier publications is different methodology (study size, number of outcomes, no loss to follow-up, repeat dietary assessment in women, distinguishing between different types of dairy products, etc) as described above. Moreover, in a previous response (http://www.bmj.com/content/349/bmj.g6015/rr/779932), we have already described the old intriguing results from reducing gastric ulcer disease pain by drinking milk. Fifty years ago, such a diet to reduce the symptoms from peptic ulcers was reported to increase the risk of myocardial infarction (19). Thus, based on autopsy data both from the United States and Great Britain the relative risk of myocardial infarction was more than doubled in ulcer patients prescribed a milk diet compared with ulcer patients without such a diet (19). By use of data provided in the original publication (19), the RRs can be calculated to 2.3 (95% CI 1.4-4.0) and 4.7 (1.4-15.3), respectively. The pooled RR estimate is 2.6 (1.6-4.3). In addition, although ecological studies should be interpreted cautiously, both cardiovascular disease mortality and hip fracture rates have additionally displayed positive associations with lactose and milk intake (20-23). Therefore, clear indications that high milk consumption could negatively affect our health have long existed. Our study can, however, not prove causality and it should not be used for dietary advice but it is one piece in a scientific puzzle.
Regarding previous publications using the Swedish Mammography Cohort, Patterson et al (24) used the second FFQ in late 1997 as the baseline investigation. We don’t find these previous study findings conflicting with our new results. A high total dairy consumption conferred a lower risk of myocardial infarction (1392 cases of MI) during 12 years of follow-up. On average, only one fourth of the total dairy servings consumed was non-fermented milk. Since we also found a reduced risk of cardiovascular mortality with high cheese and fermented milk product intake, the results are not incompatible. However, highest (median 3.1 serving per day) compared with lowest category of milk intake (median 0.1 serving per day) in the Patterson study was associated with an age-adjusted HR of 1.17 (95% CI 0.99-1.39), with a p for trend across categories of 0.02. When other dairy products were considered in the model, the estimate remained essentially similar (HR 1.15; 95% CI 0.96-1.38). Although Patterson examined MI and we mortality (including cardiovascular mortality), the results from the two studies are definitely compatible given the single FFQ used in the Patterson analysis, a lower number of outcomes compared with our mortality analysis and a somewhat more heterogenic outcome (myocardial infarction compared with death). Accordingly, the claim by Arne Astrup and Ian Givens that “In the study by Patterson et al. (2013) there was not even a trend for an increased MI risk for high intakes of milk”, is untrue. We note with interest that these authors also reference the incorrect calculations of crude mortality made by Staffan Hellstrand, who is consultant for the Federation of Swedish Farmers, an organization who is owner of milk industries (e.g., Arla Foods). In a previous response (http://www.bmj.com/content/349/bmj.g6015/rr/779932), we have corrected Staffan Hellstrand and guided him to the correct data for use. Despite erroneous figures, Astrup and Givens have chosen to repeat the presentation of Staffan Hellstrand’s incorrect calculations – an interesting action given the fact that Arne Astrup should be an objective key opinion leader in field of nutritional research by his role as editor of the American Journal of Clinical Nutrition. Hopefully, his action to criticize our study by distorted arguments is not related to his financial conflicts of interest, for example research support from Arla Foods (25). In addition, we focused on deaths and fractures as outcomes in our study. Presentation of all possible outcomes and references, including bladder cancer, stroke and colorectal cancer, would not have been feasible given both relevance and space limitations. By the second last sentence under “Mystery one”, Astrup and Givens expose their lack of knowledge in epidemiology since they obviously have not understood the time-updated Cox’s regression analysis in our use of the Swedish Mammography Cohort data.
This part of Astrup’s and Givens criticism deals with the apparent paradox of similar average BMI levels of the different milk categories despite higher calculated energy intake in high consumption categories and without higher estimated metabolic equivalents (MET-hours/days). Astrup and Givens claim that we did not comment on this paradox but our comment can be found, including four references to meta-analyses of both cohort and randomized clinical trials, in the first 9-line long paragraph of the Discussion under the subheading “Comparison with other studies”. On average, in both the cohort studies and in the randomized clinical trials - despite a higher energy intake - no weight gain has been observed with high dairy consumption. Interestingly, the authors themselves have been involved in studies where they have found higher energy intakes with high consumption of dairy products accompanied by lower body mass index (26, 27). This fact was not discussed and not even mentioned in the cohort study by Ian Givens et al (26). Nonetheless, the mechanism behind this paradox is not at present known but may involve fecal excretion of fat by soap formation with calcium (28), as also discussed by Ian Givens and Arne Astrup previously (27, 29).
We would also draw the attention to the results for cheese and fermented milk products. High consumption of these products was also associated with a higher total energy intake (Supplementary table A and B; http://www.bmj.com/content/bmj/suppl/2014/10/30/bmj.g6015.DC1/mick020390...) whereas the mortality and fracture rates were lower compared with a low consumption of these products (Supplementary Table C and D). Moreover, if selective underreporting of body weight was the case in the high consumption category, a higher BMI should not be related to a higher hip fracture risk but to a lower risk (30, 31).
Selective underreporting of body weight in the high consumption categories of dairy products is, nevertheless, unlikely. Indeed, since 5022 of the women in the Swedish Mammography Cohort during the period 2003-2009 have been involved in a clinical examination including measurement of body height and weight as well as determination of body composition by DXA (32), we have had the possibility to accurately examine BMI levels by categories of milk intake. Measured average BMI by categories of milk intake was 25.8 (SD 4.2) kg/m2 in the first category of milk intake (<1 glass per day), 26.2 (SD 4.3) kg/m2 in the second category (1 to <2 glasses/day), 26.3 (SD 4.4) kg/m2 in the third category (2 to <3 glasses/day), and 26.0 (SD 4.1) kg/m2 in the highest category of milk intake (3 glasses or more per day). Therefore, the assumption made by Astrup and Givens that women in the highest category actually have a higher BMI is not correct. Moreover, Astrup and Givens again make a gross exaggeration by stating that self-reported weight “produce a severe under-reporting of weight” with reference to the study by Kuskowska-Wolk et al (33). Based on reports from residents in a health care centre, body weight was underreported in that study but the extent of underreporting and the degree of misclassification even by the selective recruitment of the participants is highly unlikely to explain more than small differences in mortality rates (34). A modest underreporting of actual body weight (<2 kg) is also well-known in population-based settings (35) but, again, the magnitude is not able to explain our higher risk of mortality and fractures. In conclusion, the non-differential underreporting in reported body weight by dairy categories is therefore not a probable explanation for our findings.
Misreporting of dietary items was also discussed in our previous response (http://www.bmj.com/content/349/bmj.g6015/rr/779932) and we used the established method as suggested by Walter Willett to compensate for overall under- or overreporting (36, 37).
Finally, we find it remarkable that two researchers with a focus on nutrition research do not find more interest and curiosity in our findings and instead devote themselves to distort the truth. Distorting evidence will not in the long run benefit anyone; neither will hiding one’s head in the sand ignoring potentially important results.
Many of the Rapid responses include comments that disqualify the thorough work effort made by the BMJ reviewers (including a statistical reviewer) and the editorial team who have scrutinised our manuscript before allowing it to be published. We look forward to a scientific debate based not on opinion but rather on peer-reviewed scientific results and encourage researchers with information on dairy data to perform additional analyses where intake from non-fermented milk, fermented milk and cheese is analysed separately.
Karl Michaëlsson, Professor of Medical Epidemiology
Alicja Wolk, Professor of Nutritional Epidemiology
Liisa Byberg, Associate Professor of Medical Epidemiology
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Competing interests: No competing interests
We read with interest your article regarding milk intake and associations with various morbidities. The results were unexpected and raise concern regarding potential implications towards a decrease in milk intake that may not be appropriate. Previously published meta-analysis analyzing milk intake and fractures, cardiovascular disease, and mortality showed no apparent patterns towards increase in fractures or mortality. [1,2,3]
There are several confounders missing from the study that may bias results in these cohorts. Food intake, specifically red meat consumption, vegetable intake and alcohol consumption may have added valuable information. Family history, gravity and parity, and genetic variability also need to be considered. In addition, it is unpredictable whether the model relating negative effects of D-galactose seen in the animal model described can be translated to the human metabolism and cannot be concluded as such.
The published negative results of milk intake above 3 glasses per day yield potential harms including development of other vitamin deficiencies due to the 22 other essential nutrients that milk contains.  As an observational study, results published have limits of applicability not only to other ethnic populations but may be so biased as to be inapplicable to the presented cohorts; data need to be interpreted with significant caution and should not change dietary practice at this time.
1 Bischoff-Ferrari HA, Dawson-Hughes B, baron JA, Kanis JA, Orav EJ, Staehelin HB et al. Milk intake and risk of hip fracture in men and women: a meta-analysis of prospective cohort studies. J Bone Miner Res 2011;26:833-839.
2 Kanis JA, Johansson H, Oden A, De Laet C, Johnell O, Eisman JA, et al. A meta-analysis of milk intake and fracture risk: low utility for case finding. Osteoporos Int 2005;16:799-804.
3 Soedamah-Muthu SS, Ding EL, Al-Delaimy WK, Hu FB, Engberink MF, Willett WC, et al. Milk and dairy consumption and incidence of cardiobascular diseases and all-cause mortality: dose-response meta-analysis of prospective cohort studies. Am J Clin Nutri. 2011;93:158-171.
4 Heaney RP. Dairy and bone health. J Am Coll Nutr 2009;28:82S-90S.
Competing interests: No competing interests
To the editor:
We read the article by Michaelsson and colleagues1 with concern, since ‘dairy foods’ is a key food group recommended for a healthy diet in the UK2. Although calcium is found in other foods, milk is important from a public health perspective because the calcium, present naturally, is well-absorbed’ and milk contains other nutrients (eg zinc, riboflavin, potassium). Full-fat milk and cheeses provide fat-soluble vitamins, whereas low-fat dairy products are an important component of the DASH diet in helping reduce hypertension3. They are included in recent guidelines on the primary prevention of stroke4 and it is argued that the potassium requirements in the US could not be met without milk5. Boyd Orr promoted the introduction of free milk into schools in the UK in the 1930s, leading to the School Milk Act of1946, which helped improve the nutrition of all children. This strategy reached the poorest children and is believed to be a factor in the elimination of rickets. Although the practice discontinued in the 1970s, there are still calls for its re-introduction. For the edentate elderly, milk is an ideal food as it does not require chewing and provides an important source of many nutrients. We were alarmed by the strength of the association between milk intake and mortality in this very large study, showing a doubling of risk for the highest category of milk intake (although only 9% of the female study population) compounded by a linear relationship indicating that compared to no milk intake, between 1-2 glasses of milk daily increased mortality in women by 30%. The findings if true would impact greatly on public health.
We question the rationale of the analysis, the robustness of the tools used to assess milk intake, and the selective nature of the analysis undertaken.
Milk intake was assessed using a food frequency questionnaire, comprising a list of 96 foods and beverages, of which milk was one. Participants were asked how much milk they consumed based on a serving size of 200 mls. It is uncertain whether each individual’s perception of portion size is identical, and unclear whether milk added to tea and coffee and cereal (particularly difficult to assess 6) was included.
The association was adjusted for ‘healthy eating pattern’ but not dietary fat (which increased with increasing category of milk for women), nor caffeine intake (although caffeine was associated with increased fracture risk in the same cohort of women7). In the UK we do not fortify milk, whereas in Sweden, milk may be fortified with retinol (vitamin A). In the late 1990s , vitamin A was found to be associated with increased fracture risk 8, and since 2005 UK advice has been to limit intakes for people at risk of osteoporosis 9.
Most importantly is the rationale behind the selective analysis: in separating milk from fermented dairy products (yoghurts). The possibility that the detrimental effects of milk could be due to galactose was a primary reason behind the analysis. The monosaccharide galactose is produced from lactose in milk, by the action of lactase in the gastrointestinal tract. The authors argue that because lactose is removed during the fermentation process, yogurts and other fermented dairy products would not pose the same risk. The authors found no association between fermented dairy products and mortality which helped support their hypothesis. The premise of their hypothesis is inconsistent with the lactose and galactose content of these foods (table) which clearly shows that fermented milk products contribute as much galactose as milk.
Foods where dried milk is added (biscuits, pancakes, many food coverings such as breadcrumbs/ batter) and milk chocolate, would also contribute to lactose intakes. These should not be ignored if one wanted to test whether milk sugars are detrimental for health. Yet even if that analysis were done, it should be interpreted with caution as it may simply reflect an overall poor quality diet.
Anxiety has been raised by the controversy that calcium supplements increase mortality risk, but there was reassurance that dairy products did not pose the same risk10. Michaelsson’s article may lead the public to avoid milk, but it is not based on sound science. Not only are the data observational, the tools inexact, the product somewhat different to that consumed in the UK, and the high consuming group comprising less than 10% of the women’s population; but any selective analysis based on a priori hypothesis of galactose should, at the very least, have been done on all milk products including yoghurts, and not on milk alone.
1. Michaelsson K, Wolk A, Langenskiold S, et al. Milk intake and risk of mortality and fractures in women and men: cohort studies. BMJ 2014;349:g6015.
2. Your guide to the eatwell plate booklet. Public_Health_England, 2014. (Accessed 27 Nov 2014, at https://www.gov.uk/government/uploads/system/uploads/attachment_data/fil....)
3. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. New Eng J Med 1997;336:1117-24.
4. Meschia JF, Bushnell C, Boden-Albala B, et al. Guidelines for the Primary Prevention of Stroke: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke; a journal of cerebral circulation 2014.
5. Rafferty K, Heaney RP. Nutrient effects on the calcium economy: emphasizing the potassium controversy. J Nutr 2008;138:166S-71S.
6. Macdonald HM, Garland A, Burr J, et al. Validation of a short questionnaire for estimating dietary calcium intakes. Osteoporosis international 2014;25:1765-73.
7. Hallstrom H, Wolk A, Glynn A, Michaelsson K. Coffee, tea and caffeine consumption in relation to osteoporotic fracture risk in a cohort of Swedish women. Osteoporos Int 2006.
8. Melhus H, Michaelsson K, Kindmark A, et al. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med 1998;129:770-8.
9. SACN. Review of dietary advice on vitamin A by the Scientific Advisory Group on Nutrition. London: TSO; 2005.
10. Reid IR, Bolland MJ, Avenell A, Grey A. Cardiovascular effects of calcium supplementation. Osteoporos Int 2011;22:1649-58.
Helen M Macdonald
Competing interests: HMM - member of nutrition and lifestyle forum of the National Osteoporosis Society (voluntary)
The observational study by the Swedish surgeon Karl Michaëlsson and co-workers published in British Medical Journal concluded that high milk intake was associated with increased risk of bone fractures and mortality (Michaëlsson 2014). The message gave rise to global media attention, not least due to the fact that the results of the study seem to go against previous systematic reviews, meta-analyses and recommendations from most authorities in the world.
But are the new findings valid and do they change our view on dairy in any way? Or is the study flawed, or are there reasons simply to look at the result as just an outlier that needs to be viewed in the context of the totality of evidence? We have analysed the publication and the population studies behind the data.
The study is based on analyses of two Swedish population cohorts, the Swedish Mammography Cohort (SMC), and the Cohort of Swedish Men (CSM) that were followed for a mean of 20 years. At baseline in 1987-90, and 1997, respectively, various pieces of information were recorded including self-reported information about dietary intakes, and this information was analysed in relation to subsequent health outcomes. In both cohorts all subjects ranged from middle aged to elderly at baseline.
The positive findings
The intake of cheese and fermented milk products was associated with a reduced mortality and a reduced risk of fractures. For each serving, the rate of mortality and hip fractures was reduced by statistically significant 10-15 %, which is consistent with other studies.
The negative findings
For every glass of milk the women reported to drink at baseline it was found, after various adjustments, that they had a 15 % higher mortality in the subsequent 20 years, and a 3 % higher mortality for males. They also found that for every glass of milk women had a 2 % higher risk of all fractures, and a 9 % higher risk of hip fractures, whereas no such significant risk was found among the males. But how do these results fit with the totality of evidence on cardiovascular risk and mortality?
A single study versus totality of evidence
Two recent meta-analyses have analysed all available observational studies. Based on 26 studies O’Sullivan et al. (2013) concluded that dairy and milk intake had neither any effect on total mortality nor cardiovascular mortality. Soedamah-Muthu et al. (2011) also did a meta-analysis of 17 prospective cohort studies and found a modest inverse association between milk intake and risk of overall cardiovascular disease i.e. a 6 % decrease in risk per 200 mL/day. But milk intake was not associated with risk of CHD, stroke or total mortality. They concluded that their dose-response meta-analysis of prospective studies indicated that milk intake is not associated with total mortality, but may be inversely associated with overall CVD risk. A meta-analysis of milk intake and risk of hip fractures could not find any increased risk (Bischoff-Ferrari et al., 2011), but systematic reviews involving totality of evidence conclude that dairy is an important contributor to bone health (Weaver 2014). It is also worth remembering that osteoporosis is a ʻpediatric disease with geriatric consequencesʼ (Power et al.,1999) with good evidence that low milk and hence low calcium intake during childhood/adolescence is associated with significantly increased risk in middle and older age, particular in women (e.g. Kalkwarf et al., 2003). Thus in middle aged and older women it may not be surprising that that increased milk intake did not reduce the risk fractures although a recent study challenges this (Sahni et al., 2014). They reported that a total of 830 men and women (mean age at baseline 77 years) from the Framingham Original Cohort, completed a food-frequency questionnaire in 1988 to 1989 and were followed for hip fracture rate until 2008. Those with medium (>1 and <7 servings/wk) or higher (≥7 servings/wk) milk intake tended to have lower hip fracture risk than those with low (≤1 serving/wk) intake (high versus low intake HR 0.58, 95% CI 0.31–1.06; medium versus low intake HR 0.61, 95% CI 0.36–1.08; p trend = 0.178). There appeared to be a threshold for milk, with a 40% lower risk of hip fracture among those with medium/high milk intake compared with those with low intake (p = 0.061). A similar threshold effect was observed for milk plus yogurt intake. These results do indeed suggest that greater intakes of milk and milk + yogurt may lower risk for hip fracture in older adults.
These conclusions are supported by several newer observational studies using objective biomarkers for dairy intake, and they have strengthened the evidence from observational and intervention studies to support that dairy reduces risk of type 2 diabetes and CVD (Astrup 2014, AJCN).
We have identified several shortcomings and limitations that can be found in most, if not all, observational studies. However, we have identified two mysteries that go beyond our scientific skills and capacity to explain:
Since this study is clearly an outlier it is reasonable to consider if there is something special regarding the health effects of dairy in the Swedish population. The answer to this question is interestingly enough found in publications from another research group in Sweden that has published similar results from exactly the same study populations, although of somewhat smaller sizes.
Patterson et al. (2013), who also used the Swedish Mammography Study of ~33,000 women found that total dairy intake at baseline was inversely associated with risk of myocardial infarction (MI) when comparing highest versus lowest quintile during 11.6 years follow up (HR 0.77; 95% CI, 0.63-0.95). Also cheese intake was inversely associated with MI (HR 0.74; 95% CI, 0.60-0.91). Interestingly, butter on bread, but not butter on cooking, was associated with an increased risk (HR 1.34; 95% CI, 1.02-1.75). The latter finding is highly suggestive of a confounding effect of starchy carbohydrates i.e. white bread intake, as Jacobsen et al. (2010) have reported that replacement of saturated fat with refined carbohydrate increases CVD risk. In the study by Patterson et al. (2013) there was not even a trend for an increased MI risk for high intakes of milk. In another analysis from the same research group Larsson et al. (2012) examined dairy intake and risk of the other CVD end-point stroke in the both the SMC (also used by Patterson et al. (2013)) and CSM cohorts with a mean 10.2 years follow up. She found that low-fat dairy was associated with reduced risk for total stroke, whereas there was no effect of other dairy products. Again milk intake was not significantly positively associated with stroke, but with RR values of 0.92-0.94 (P=0.15) there was a suggestion a possible small protective effect, if anything (Larsson et al., 2012). Moreover there was a significant negative association between low-fat dairy and total stroke (RR 0.88; CI 0.80-0.97, P=0.03). It is also very interesting to note that if the mortality data in the paper of Michaëlsson et al. (2014) are expressed as a simple proportion of the population that died; increasing milk intake is associated with a linear decrease in mortality while the reported age-adjusted HR shows a similar linear but increasing mortality with increasing reported milk intake (See commentary by Hellstrand above).
The same group have also examined the potential role of dairy for risk of major cancers with possible protective role of dairy for bladder and colorectal cancers using the same to cohorts. Again, total dairy intake was not significantly associated with risk of bladder cancer, but sour milk and yogurt intakes were associated with a significant 38 % lower risk in men and women combined (Larsson et al., 2008). For milk there was no signal of any increased risk, only a non-significant lower risk. In another paper they reported that total dairy intake was associated with reduced risk of colorectal cancer in men, and more than 7 servings/d of total dairy foods compared with less than 2 servings were associated with a 57 % lower risk of colonic cancer (Larsson et al., 2006). A recent meta-analysis of 19 cohort studies also concluded that increased intake of milk and dairy products was associated with reduced colorectal cancer risk reporting summary RR of 0.83 (CI, 0.78–0.88) per 400 g/day of total dairy products and 0.91 (0.85–0.94) per 200 g/day of milk (Aune et al., 2012)
So studies using both the SMC and CMS cohorts, with a shorter follow-up and smaller cohort size than the recent BMJ study, show significantly lower risk of major CVD and cancers for those who consumed higher amounts of dairy, and with no indication of any possible increased risk for high milk intakes. It is unfortunate that the authors of the BMJ paper did not comment on these previous findings from the same cohorts, and failed to present data on both cancer and CVD incidence (relying only on mortality), including details on site specific cancers and strokes and MI. They actually do not even cite that papers in their discussion of their results, despite the fact that the opposing results from these cohorts relied on the same baseline dietary recordings.
From a scientific point of view it is very unusual that a longer follow up i.e. 10 years versus 20 years follow up completely turns the results upside down, particularly when no new information of dietary intake is added during follow up so the impact of changes in intakes can be addressed. There are concerns however that dietary data collected at baseline will be less representative of habitual diet after 20 years than after 10-11 years. Although the SMC cohort was larger in size in the BMJ analyses, the discrepancy with other results from the same cohorts severely questions the validity of the analyses and statistics, and calls for a re-analyses of all data by independent scientists.
The validity of self-reported information about dietary intake is a major problem in population studies, and failure to address this may lead to false conclusions (Dhurandhar et al., 2014). Some “sensitivity analyses” are normally required to avoid false conclusions being made due to statistical artefacts that occur due to a systematically biased under- and over-reporting. It is well-known that all people are prone to underreport unhealthy foods and drinks, and over-report food and drinks considered as healthy. It is impossible to take misreporting into account and adjust for it unless there are measurements of objective biological markers. This has not been done in the Swedish studies, so we can just do some basic validity assessments.
Are the baseline characteristics of the participants in the different quintiles of dairy food consumption comparable and consistent with basic physiological principles? Across the quintiles of dairy intakes BMI is very similar, and so is Total Physical Activity (MET-h/day), so consequently these groups are supposed to have similar basal metabolic rate, and total energy expenditure, which means that they should have same total energy requirements. However, with increasing intake of dairy intake total energy intake goes significantly up i.e. from 1412 to 1965 kcal/day in lowest to highest quintile of dairy intake, a difference of 553 kcal/day (or 39 %). In a previous publication reporting on the same study (Larsson et al., 2012), also here BMI and physical activity were identical across the quintiles of dairy food intakes, but total energy intake went from 1709 to 3013 kcal/day from lowest to highest intake of dairy (76 %).
The authors of the studies do not comment on this paradox, except saying that it is well-known that a high intake of dairy is not associated with increase in body weight and BMI. However, according to thermodynamic laws, it is obvious that the existence of two weight stable groups of persons with same BMI, physical activity level and energy requirements cannot exist when one group is consuming ~50 % more energy than the other. It is a violation of the laws of thermodynamics. However, there is a very sensible explanation: all information about height and weight in the Swedish cohorts are self-reported, which is well known to produce a severe under-reporting of body weight among the overweight and particularly obese individuals (Kuskowska-Wolk & Rössner, 1989).
It means that the true BMI across the quintiles would be increasing, and that total energy intake, and intakes of most foods would go up. An increased BMI causes an increased mortality due to both cancer and CVD. So the most likely explanation for the findings are that the authors have in reality studied, not the effect of high dairy intakes, but the results of being obese. It would be interesting to invite subsets of the participants of these studies to a measured height and weight to get this hypothesis tested.
Professor Arne Astrup Professor D Ian Givens
Astrup A. A changing view on saturated fatty acids and dairy: from enemy to friend. Am J Clin Nutr. 2014 Dec;100(6):1407-8.
Aune D, Lau R, Chan DS M, Vieira R, Greenwood DC, Kampman E and Norat T. (2012) Dairy products and colorectal cancer risk: a systematic review and meta-analysis of cohort studies. Annals of Oncology 23: 37–45.
Bischoff-Ferrari HA, Dawson-Hughes B, Baron JA, Kanis JA, Orav EJ, Staehelin HB, Kiel DP, Burckhardt P, Henschkowski J, Spiegelman D, Li R, Wong JB, Feskanich D, Willett WC (2011) Milk intake and risk of hip fracture in men and women: a meta-analysis of prospective cohort studies. J Bone Miner Res 26:833-839.
Dhurandhar NV, Schoeller D, Brown AW, Heymsfield SB, Thomas D, Sørensen TI, Speakman JR, Jeansonne M, Allison DB (2014) Energy balance measurement: when something is not better than nothing. Int J Obes Epub ahead of print doi: 10.1038/ijo.2014.199.
Jakobsen MU, Dethlefsen C, Joensen AM, Stegger J, Tjønneland A, Schmidt EB, Overvad K. Intake of carbohydrates compared with intake of saturated fatty acids and risk of myocardial infarction: importance of the glycemic index. Am J Clin Nutr. 2010 Jun;91(6):1764-8.
Kalkwarf H J, Khoury JC and Lanphear BP (2003) Milk intake during childhood and adolescence, adult bone density, and osteoporotic fractures in US women. Am J Clin Nutr 77:257–65.
Kuskowska-Wolk A, Rössner S. The "true" prevalence of obesity. A comparison of objective weight and height measures versus self-reported and calibrated data. Scand J Prim Health Care. 1989 Jun;7(2):79-82.
Larsson SC, Bergkvist L, Rutegård J, Giovannucci E, Wolk A (2006) Calcium and dairy food intakes are inversely associated with colorectal cancer risk in the Cohort of Swedish Men. Am J Clin Nutr 83:667-673.
Larsson SC, Andersson S-O, Johansson J-E, Wolk A (2008) Cultured milk, yogurt, and dairy intake in relation to bladder cancer risk in a prospective study in Swedish women and men. Am J Clin Nutr 88:1083-1087.
Larsson SC, Virtamo J, Wolk A (2012) Dairy consumption and risk of stroke in Swedish women and men. Stroke 43:1775-1780.
Michaëlsson K, Wolk A, Langenskiöld S, Basu S, Lemming EW, Melhus H, Byberg L (2014) Milk intake and risk of mortality and fractures in women and men: cohort studies. BMJ 349:g6015.
O'Sullivan TA, Hafekost K, Mitrou F, Lawrence D. Food sources of saturated fat and the association with mortality: a meta-analysis. Am J Public Health. 2013 Sep;103(9):e31-42. doi: 10.2105/AJPH.2013.301492.
Patterson E, Larsson SC, Wolk A, Åkesson A (2013) Association between dairy food consumption and risk of myocardial infarction in women differs by type of dairy food. J Nutr 143:74-79.
Power ML, Heaney RP, Kalkwarf HJ, Pitkin RM, Repke JT, Tsang RC and Schulkin J (1999) The role of calcium in health and disease. Am J Obstet Gynecol 181:1560–1569.
Sahni, S., Mangano, K. M., Tucker, K. L., Kiel, D. P., Casey, V. A. and Hannan, M. T. (2014), Protective Association of Milk Intake on the Risk of Hip Fracture: Results from the Framingham Original Cohort. J Bone Miner Res, 29: 1756–1762. doi: 10.1002/jbmr.2219
Soedamah-Muthu SS, Ding EL, Al-Delaimy WK, Hu FB, Engberink MF, Willett WC, Geleijnse JM. Milk and dairy consumption and incidence of cardiovascular diseases and all-cause mortality: dose-response meta-analysis of prospective cohort studies. Am J Clin Nutr 2011;93:158-71.
Weaver CM. How sound is the science behind the dietary recommendations for dairy? Am J Clin Nutr. 2014 May;99(5 Suppl):1217S-22S.
Competing interests: Arne Astrup: He is a member of the Scientific Advisory Board of Global Dairy Platform, USA, and have received speakers honorarium for dairy related presentations. He’s department receives research funds from several dairy foundations and companies. Ian Givens: Current dairy food related research is funded by competitive research grants from the Medical Research Council (MR/K020218/1), DairyCo/Dairy Council, the Biotechnology and Biological Sciences Research Council (BBSRC) with contributions from various industries. I have no other relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript’
Hello, it would be interesting to know if there is a difference between homogenized milk and non-homogenized milk. The grease in homogenized milk is very much split and is probably much easier taken up by the body than from normal milk. Is this examined in the study?
Competing interests: No competing interests
We read with interest the article by Karl Michaëlsson et al.1 We had a chance to view the role of milk from a different perspective. It reminded me of a funny story about Chinese people imitating Europeans. Leon The Professional, a famous French film starring Jean Reno, impressed Chinese audiences with a special detail that Leon, a seemingly omnipotent mob hitman, maintained a good habit of drinking a large amount of milk for decades. It really played an active role in encouraging Chinese adults and teenagers to drink milk every day.
However, the result of this latest cohort study indicates that high milk intake is associated with higher mortality and fracture incidence in women. Meanwhile, Professor C Mary gives a further explanation that people who consume milk are similar to those who consume yogurt or cheese, therefore it is less likely that there would be confounding factors between consumers of fermented milk products and consumers of milk, such as accidents. 2
Actually, I’d like to provide a seemingly ridiculous interpretation that the daily total volume drunk could cause different fracture incidences in different categories of daily milk intake. It is reasonable to hypothesize that people with a higher daily milk intake are likely to drink a higher daily volume leading to much more frequent use of the bathroom, especially during the night, which could account for the higher risk of hip fracture. Of course, this interpretation could also explain the difference between consumers of fermented milk products and those consuming milk. If Professor Karl Michaëlsson and his colleague could analysis the data on daily volume intake and physical activities causing the fracture, we could know whether this interpretation is ridiculous or reasonable.
1 Michaelsson K, Wolk A, Langenskiold S, Basu S, Warensjo LE, Melhus H, et al. Milk intake and risk of mortality and fractures in women and men: cohort studies. BMJ (Clinical research ed.) 2014;349:g6015.
2 C Mary. Milk and mortality Genetic studies could help us interpret a biologically plausible but preliminary association. BMJ2014;349:g6205.
Competing interests: No competing interests
Thank you for your invitation to discuss the subject: “Milk intake and risk of mortality and fractures in women and men: cohort studies.”
I am interested in the result that a high milk intake in both sexes is associated with higher mortality and fracture rates and with higher levels of oxidative stress and inflammatory biomarkers. Such a pattern was not observed with high intake of fermented milk products.
I ask some questions.
1: Hypertension, dyslipidemia, diabetes mellitus, smoking and family history as the risk factors of cardiovascular disease are important, when I see patients suspected with cardiovascular disease. I want to know the information of the risk factors in each categories of milk intake.
The number of current smokers in the group with an intake of more than 3 glasses of milk is more than that in the group with an intake of less than 1 glass of milk in this paper. The number of current smokers may affect the results.
2: Bone density, serum calcium, total protein and albumin are important, when I see patients with bone fracture. I want to know the information on bone density, serum calcium, total protein and albumin in each category of milk intake.
The number of users of calcium and vitamin D supplements in the group with an intake of less than 1 glass of milk is more than that in the group with an intake of more than 3 glasses of milk in this paper. The dose of supplements may affect the results.
Competing interests: No competing interests
Based on your invitation, I read with interest the nice paper by Michaëlsson et al. about milk intake and risk of mortality and fracture. Considering some comments may elucidate small details. They have mentioned that “For every glass of milk in women no reduction was observed in … or for hip fracture (1.09, 1.05 to 1.13)”. However, their confidence interval does not contain one and it shows that it is significant.
It is not determined are subsamples of cohorts selected randomly or was there any selection bias?
Women are selected from a mammography cohort. Surveillance bias in such a research scenario may be a possible cause for more detailed evaluation in these participants and findings fractures which we were not able to detect in a usual clinical scenario. Moreover, selection bias due to participating interested cases to their health or cases with problems in their health seeking a support from a study may have caused selecting specific sample not generalizble to the general population. Non-response bias can also be another source of selection bias in this study as 46.8% (45339/(100303-3511)) of men and 46.1% (39227/(90303-5218)) of women did not completely participate in all phases of the study.
All of above mentioned scenarios could be find behind the rationalization of the present study.
1. Michaelsson K, Wolk A, Langenskiold S, et al. Milk intake and risk of mortality and fractures in women and men: cohort studies. BMJ (Clinical research ed) 2014;349:g6015 doi: 10.1136/bmj.g6015[published Online First: Epub Date].
correspondence to: email@example.com
Competing interests: No competing interests
Second reply to commentaries regarding our manuscript “Milk intake and risk of mortality and fractures in women and men: cohort studies”
We again thank all authors for their comments. Some of the comments have already been addressed in our previous response (1).
Stefan Hellstrand is suspicious that our statistical analyses might have distorted reality. The statistical analyses we have performed are standard procedures in epidemiological research. In his attached Figure 1, Hellstrand has calculated risks by combining information in Tables 1 and 2 to show that, in reality, there is a lower risk of mortality with higher milk intake and that the hazard ratios we present might be incorrect. Unfortunately, Hellstrand has combined the wrong data resulting in an erroneous analysis and incorrect results. Since we are using time-updated data for the cohort of women, a crude incidence rate would be obtained by dividing the number of cases with the person-time at risk in Table 2. To get a crude incidence, or risk, by using the numbers at risk in Table 1 (baseline data), these should be combined with the number of cases provided in supplemental Table H. By doing so, and by comparing with intake of <1 glass of milk, the risk ratios for total mortality would be 1.09, 1.22 and 1.22 for 1-2 glasses, 2-3 glasses and ≥3 glasses of milk, which is in line with the age-adjusted hazard ratios with results derived from only baseline data as presented in supplementary table H). Thus the statement that our data processing or analyses “change the results of consuming milk from being positive for health to being negative” is incorrect.
Hellstrand further compares the energy intake in our cohorts to the recommended intake in Sweden. Firstly, it is difficult to draw conclusions based on a comparison with ecological data. Secondly, it is unclear how Hellstrand has calculated the “fraction of subsamples that died” since this was incorrectly calculated in his Figure 1. Thirdly, and most importantly, we have used standard methods to compensate for misreporting of energy intake in epidemiological studies. This is done by first excluding those with implausible energy intake (≥3 SDs below or above the log-transformed mean energy intake) and then adjusting for total energy intake, as suggested by Walter Willett (2, 3). Willett states “Although the extremes within this range are rarely correct, adjustment of nutrient intakes for total energy intake will, to a large extent, compensate for overall underreporting or overreporting” (2). We would also draw the attention to the results for cheese and fermented milk products. High consumption also of these products was associated with also a higher total energy intake whereas the mortality and fracture rates were lower compared with a low consumption of these products.
Fredrika Hansson’s first question regarding lactose has been addressed in our previous response (1). Regarding the definition of outcomes, these are clearly defined in the methods section. We did not specifically study mortality after a fracture.
In response to Klaus W Aschern we would like to point out that the studies referred to regarding D-galactose were animal studies that, to the best of our knowledge, seem to be carefully conducted. He further speculates that a high intake of milk might reduce intake of other foods with positive health effects. The associations presented in the article were independent of a healthy eating pattern and also many nutrients, as shown in Appendix Table E.
Siddappa Gada proposes a prospective study to study various dietary products on mortality. Indeed, our study is a prospective study where participants indicated their consumption of milk and other dairy products and were followed until fracture or death. A long-term randomised study with exclusive adherence to separate dietary products is unlikely to ever be well performed.
Bodo C. Melnik presents an interesting alternative hypothesis as an explanation for our findings. An intriguing question arises – what is the concentration of microRNA in cheese and fermented milk products compared with that in non-fermented milk?
Henning K Antonsen proposes that gastroesophageal reflux or ulcer disease or its treatment might be the underlying cause of our findings since his patients relieve their symptoms by drinking milk. Interestingly, 50 years ago such diet to reduce the symptoms from peptic ulcers was reported to increase the risk of myocardial infarction (4). Thus, based on autopsy data both from the United States and Great Britain the relative risk of myocardial infarction was more than doubled in ulcer patients prescribed a milk diet compared with ulcer patients without such a diet (4). By use of data provided in the original publication (4), the RRs can be calculated to 2.3 (95% CI 1.4-4.0) and 4.7 (1.4-15.3), respectively. The pooled RR estimate is 2.6 (1.6-4.3).
Moreover, whether proton pump inhibitors increase the risk of fragility fractures have been debated since some years. A recent review of the current evidence concluded that patients prescribed PPI therapy tend to be more frail with more risk factors for fractures than those not given these drugs and it is probable that PPI therapy is not an independent risk factor for fracture (5). Even though a surrogate measure for fracture, bone mineral density in a RCT was significantly higher in a group that received PPI along with risedronate compared with those on risedronate alone (6). Nonetheless, we found no indication that high consumers of milk had been prescribed PPIs more frequently than low-consumers of milk (Attached Table 1).
1. Michaëlsson K, Byberg L. Reply to commentaries regarding our manuscript "Milk intake and risk of mortality and fractures in women and men: cohort studies". BMJ. 2014;349:g6015.
2. Willett W. Nutritional epidemiology. 3rd ed. Oxford University Press: Oxford; 2013.
3. Willett WC, Howe GR, Kushi LH. Adjustment for total energy intake in epidemiologic studies. Am J Clin Nutr. 1997;65(4 Suppl):1220S-8S.
4. Hartroft WS. The Incidence of Coronary Artery Disease in Patients Treated with Sippy Diet. Am J Clin Nutr. 1964;15:205-10.
5. Leontiadis GI, Moayyedi P. Proton pump inhibitors and risk of bone fractures. Curr Treat Options Gastroenterol. 2014;12(4):414-23.
6. Itoh S, Sekino Y, Shinomiya K, Takeda S. The effects of risedronate administered in combination with a proton pump inhibitor for the treatment of osteoporosis. J Bone Miner Metab. 2013;31(2):206-11.
Competing interests: No competing interests