Summary of points raised by this research:
- Milk (non-fermented) worsens oxidative stress and inflammation
- Fermented milk (sour milk and yoghurt) reduces oxidative stress and inflammation
- Drinking unfermented milk did not reduce the risk of fractures - in fact the reverse was observed!
- D-Galactose is highlighted as a possible explanation for the health differences between fermented milk and non-fermented milk. Unfermented milk is a major dietary source of D-Galactose. Galactose has been shown in animals to accelerate ageing and worsen oxidative stress.
Milk intake and risk of mortality and fractures in women and men: cohort studies
BMJ 2014; 349 doi: http://dx.doi.org/10.1136/bmj.g6015 (Published 28 October 2014)
Abstract
Objective:
To examine whether high milk consumption is associated with mortality and fractures in women and men.
Design:
Cohort studies.
Setting: Three counties in central Sweden.
Participants: 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), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997.
Main outcome measure:
Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture.
Results:
During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker).
[following are some quotes from the body of the full text article]
Conclusions:
High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.
High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.
Biomarkers
D-galactose supplementation in animals has been shown to increase oxidative stress and inflammation.4 5 6 7 To assess the association between milk intake and biological markers of oxidative stress and inflammation
[...]
Milk intake, oxidative stress, and inflammation
We further investigated whether milk intake was associated with oxidative stress and inflammation. Milk intake was positively associated with 8-iso-PGF2α in both sexes, and with interleukin 6 in men (fig 4⇓). Consumption of fermented milk products (soured milk and yogurt) indicated a negative relation with both the oxidative stress and the inflammatory markers (see supplementary figure C, panel A). No such association was observed with cheese intake (see supplementary figure C, panel B). Milk intake and risk of mortality and fractures in women and men: cohort studies
Results
[...] In women, higher rates were observed for death from all causes (adjusted hazard ratio 1.15, 95% confidence interval 1.13 to 1.17, for each glass of milk), cardiovascular disease (1.15, 1.12 to 1.19, for each glass of milk), and cancer (1.07, 1.02 to 1.11, for each glass of milk) (table 2 and fig 3⇓). Milk consumption corresponding to three or more glasses of milk a day (mean 680 g a day) compared with less than one glass a day (mean 60 g a day), was associated with a hazard ratio of total mortality of 1.93 (1.80 to 2.06) in women, with approximately similar estimates for cardiovascular mortality and somewhat lower for cancer mortality (1.44, 1.23 to 1.69). For women who consumed three or more glasses of milk a day the hazard ratio for any fracture was 1.16 (1.08 to 1.25) and for hip fracture was 1.60 (1.39 to 1.84).
[...]
Comparing milk with other dairy products
Particularly noteworthy is that intake of fermented milk products such as yogurt and soured milk and cheese were associated with lower rates of fracture and mortality. Furthermore, we observed a positive association only between milk intake and markers of oxidative stress (urine 8-iso-PGF2α) and inflammation (serum interleukin 6). Previously, we found a negative relation between bone mineral density and 8-iso-PGF2α.42 63 Interleukin 6 seems to be causally related to cardiovascular disease64 and may influence bone loss and osteoporosis.65 Importantly, those who consume high amounts of non-fermented milk have a more non-favourable cardiovascular risk factor profile, with higher blood pressure, lower high density lipoprotein cholesterol levels, and higher insulin resistance.18 In contrast, intake of cheese and fermented milk products is related to higher high density lipoprotein cholesterol levels, less insulin resistance, and a lower risk of myocardial infarction.18 22 23 24 In addition, a recent small randomised cross over study indicated that the intake of a fermented dairy diet seemed to provide a more favourable biomarker profile than that of a non-fermented dairy diet.66
Potential mechanism
One potential candidate for the discrepant results for different types of dairy products is D-galactose content. The intake of D-galactose from non-fermented milk is considerably higher than that from other food sources, including cheese and fermented milk products. Non-dairy sources of D-galactose are mainly cereals, vegetables, and fruits,67 but the concentration of galactose and the amount ingested from these sources accounts for a small proportion of the total intake of galactose. Put into perspective, the amount of lactose in one glass of milk corresponds to approximately 5 g of galactose, whereas the amount in 100 g of fruits or vegetables67 is measured in milligrams or tens of milligrams. D-galactose given to laboratory animals (mice, rats, and drosophila flies) is an established experimental model for premature aging, including shortened life span caused by oxidative stress and chronic inflammation,4 5 6 7 but whether this mechanism can be generalised to humans needs further scientific support. However, galactosaemia is a genetic disorder that results from loss of galactose-1P-uridylyltransferase, with accumulation of galactose in blood and other tissues as a consequence.68 69 Affected infants experience a rapid escalation of potentially lethal acute symptoms after exposure to milk, and experimental models display oxidative stress as a mechanism for the development of disease.68 Even with dietary restrictions of galactose intake these patients have higher circulating levels of galactose and an increased risk for chronic diseases in adulthood,69 including osteoporosis.70
Conclusion
A higher consumption of milk in women and men is not accompanied by a lower risk of fracture and instead may be associated with a higher rate of death. Consequently, there may be a link between the lactose and galactose content of milk and risk as suggested in our hypothesis, although causality needs be tested using experimental study designs. Our results may question the validity of recommendations to consume high amounts of milk to prevent fragility fractures.3 71 72 The results should, however, be interpreted cautiously given the observational design of our study. The findings merit independent replication before they can be used for dietary recommendations.
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