Dairy fat and its fatty acids (FAs) have been shown to possess pro-health properties that can support health maintenance and disease prevention. In particular, branched-chain FAs (BCFAs), comprising approximately 2% of dairy fat, have recently been proposed as bioactive molecules contributing to the positive health effects associated with the consumption of full-fat dairy products. This narrative review evaluates human trials assessing the relationship between BCFAs and metabolic risk factors, while potential underlying biological mechanisms of BCFAs are explored through discussion of studies in animals and cell lines. In addition, this review details the biosynthetic pathway of BCFAs as well as the content and composition of BCFAs in common retail dairy products. Research performed with in vitro models demonstrates the potent, structure-specific properties of BCFAs to protect against inflammation, cancers, and metabolic disorders. Yet, human trials assessing the effect of BCFAs on disease risk are surprisingly scarce, and to our knowledge, no research has investigated the specific role of dietary BCFAs. Thus, our review highlights the critical need for scientific inquiry regarding dairy-derived BCFAs, and the influence of this overlooked FA class on human health.
Lifestyle is a key modifiable risk factor involved in the manifestation of metabolic syndrome and, in particular, diet plays a pivotal role in its prevention and development. Current dietary guidelines discourage the consumption of saturated fat and dietary sources rich in saturated fat, such as dairy products, despite data suggesting that full-fat dairy consumption is protective against metabolic syndrome. This narrative review assessed the recent epidemiological and clinical research that examined the consumption of dairy-derived saturated fatty acids (SFA) on metabolic syndrome risk. In addition, this review evaluated studies of individual SFA to gain insight into the potential mechanisms at play with intake of a diet enriched with these dairy-derived fatty acids. This work underscores that SFA are a heterogenous class of fatty acids that can differ considerably in their biological activity within the body depending on their length and specific chemical structure. In summary, previous work on the impact of dairy-derived SFA consumption on disease risk suggests that there is currently insufficient evidence to support current dietary guidelines which consolidate all dietary SFA into a single group of nutrients whose consumption should be reduced, regardless of dietary source, food matrix, and composition.
Purpose: The prognosis of patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) remains poor, and novel therapies are needed. The proteasome pathway represents a potential therapeutic target. A phase I trial of the secondgeneration proteasome inhibitor ixazomib in combination with MEC (mitoxantrone, etoposide, and cytarabine) was conducted in patients with R/R AML.Patients and Methods: Dose escalation of ixazomib was performed using a standard 3 Â 3 design. Gene-expression profiling was performed on pretreatment and posttreatment bone marrow or blood samples.Results: The maximum tolerated dose of ixazomib in combination with MEC was 1.0 mg. The dose limiting toxicity was thrombocytopenia. Despite a poor risk population, the response rate [complete remission (CR)/CR with incomplete count recovery (CRi)] was encouraging at 53%. Geneexpression analysis identified two genes, IFI30 (g-interferon inducible lysosomal thiol reductase) and RORa (retinoic orphan receptor A), which were significantly differentially expressed between responding and resistant patients and could classify CR.Conclusions: These results are encouraging, but a randomized trial is needed to address whether the addition of ixazomib to MEC improves outcome. Gene-expression profiling also helped us identify predictors of response and potentially novel therapeutic targets.
The fatty acid (FA) composition and content of whole milk (3.25% fat) from organic, omega-3 (n-3) FA fortified, and conventional retail brands available in the northeastern U.S. were assessed monthly via gas chromatography. Among the retail labels, organic milk stood out as it contained a distinct and more healthful FA profile, consistently comprising a higher content of unique bioactive FAs (short-chain FAs, odd- and branched-chain FAs, vaccenic acid, and conjugated linoleic acids) per serving, particularly during the warm season. The total content of saturated FAs did not differ by retail label. While organic and n-3 fortified milk contained a similar content of total n-3 FAs, the proportion of individual n-3 FAs differed significantly (organic milk: 18:3 n-3; n-3 fortified milk: 20:6 n-3) as a result of the production system and process, respectively. Overall, per serving, the FA profile of organic milk may provide added nutritional and health benefits.
Background There is currently no consensus on which tissues are optimal for assessing specific diet-derived fatty acids (FAs) as biomarkers for long-term dietary studies. Objectives This study measured the content of unique diet-derived FAs from dairy, echium, and fish in tissues (adipose, muscle, liver, erythrocyte membranes, and plasma phospholipids, cholesterol esters, triglycerides, and free fatty acids) after long-term feeding in CD-1 mice. Methods Beginning at weaning, mice (n = 10–11/sex/diet) were fed 1 of 4 diets (40% kcal/total energy) that only differed in FA composition: control fat blend (CON), reflecting the FA profile of the average US American diet, or CON supplemented with 30% of fish oil (FO), dairy fat (DF), or echium oil (EO). After 13 mo, tissues were collected to determine FAs via gas–liquid chromatography. Tissue FAs were analyzed via 2-factor ANOVA, and relationships between FA intake and tissue content were assessed with Spearman correlations. Results As anticipated, 20:5n–3 (ω-3) tissue content was ≤32-fold greater in FO- compared with CON-fed mice (P < 0.05). In addition, 20:5n–3 intake strongly correlated with its content in all tissues (ρ = 0.67–0.76; P < 0.05). Echium oil intake also influenced tissue FA content in mice as expected. For example, 18:3n–6 was ≤25-fold greater in adipose, muscle, and liver tissues of EO-fed compared with CON-fed mice (P < 0.05). Tissue content of FAs typically considered biomarkers of dairy fat intake (15:0, 16:1 t9, and 17:0) was often not greater in mice fed DF than other diet groups, although 18:2 c9, t11 content was ≤6-fold greater in tissues from DF-fed compared with CON-fed mice (P < 0.05). The content of dairy-derived FAs in blood fractions of females was up to 2-fold greater compared with males, whereas docosapentaenoic acid content was up to 1-fold greater in all blood fractions and in liver tissue of males compared with females (P < 0.05). In adipose, muscle, and liver tissue, the content of γ-linolenic acid and stearidonic acid was less than 1-fold greater in females than in males (P < 0.05). Conclusions Our study indicates that the distribution of dietary FAs is tissue and sex dependent in aged CD-1 mice. Research using FA biomarkers should assess a combination of FA biomarkers to accurately validate patterns of FA intake and source.
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