[Canada's guidance on alcohol and health : A paradigm shift]. / Kanadas Leitlinienempfehlung zu Alkohol und Gesundheit : Ein Paradigmenwechsel.

Alcohol is a socially accepted food and beverage and as a cultural asset is also part of religious rituals. It can be an intoxicant and an addictive substance. It is also a noxious substance as around 3 million people worldwide die every year as a result of alcohol consumption. With the publication by Zhao et al. 2023 the relationship between the quantity of alcohol consumption and mortality reached a new level and changed the recommendations of Canada's Guidance on Alcohol and Health. The J­curve of the French paradox became a linear relationship between alcohol consumption and mortality because the review of several control groups in previous studies revealed a recruitment error from abstinent ex-drinkers. In their systematic analysis, taking this bias into account the assessment of small amounts of alcohol as a cardioprotective stimulant had to be revised. This is a paradigm shift.

Outcomes of Cemented Distal Femoral Replacement Using "Line to Line" Technique With All-Polyethylene Tibial Implant for Tumors.

BACKGROUND: Both cemented and cementless stemmed endoprosthetic implants have been used to reconstruct large skeletal defects after tumor resection with similar outcomes. In this study, we examined the oncologic, clinical, and functional outcomes in patients undergoing distal femur replacement using the French paradox technique. METHODS: A total of 125 patients who underwent distal femur replacement between 1990 and 2019 using the line-to-line cementation technique were reviewed. Implant failure was recorded as per Henderson's classification. Functional outcomes were analyzed using the Musculoskeletal Tumor Society and Toronto Extremity Salvage Score scoring systems. The mean follow-up was 84 (1-350) months. RESULTS: Aseptic loosening of the femoral stem was recorded in one patient at 21-years of follow-up. Twenty of 125 patients required bushing exchange for polyethylene wear, all after 10 years. Six tibial bearing component fractures were recorded in four patients while one femoral stem component Morse taper fractured. Two all-polyethylene cemented tibial implants were revised for polyethylene granuloma. Deep surgical site infection occurred in 13 patients, while six patients experienced local recurrence. Kaplan-Meier estimates for implant survival for all-cause revision were 85% at 1 year and 70% at 5 years. These estimates for femur or tibia loosening as an end point were 96% at 10 years and 90% at 15 years. The mean Musculoskeletal Tumor Society and Toronto Extremity Salvage Score scores at the last follow-up were 76% and 74%, respectively. Thirty-five patients died of disease progression. CONCLUSION: The line-to-line cementation technique, used with all-polyethylene tibial implants, demonstrates low incidence of aseptic loosening at medium and long-term follow-ups. LEVEL OF EVIDENCE: III.

Radiographic, Functional, and Oncologic Outcomes of Cemented Modular Proximal Femur Replacement Using the "French Paradox" Technique.

BACKGROUND: Endoprostheses are frequently used in the management of tumors involving the proximal femur. Aseptic loosening is a common complication that has been linked to the cementing technique. The "French paradox" is well-known cementing technique in the arthroplasty literature. No previous reports have assessed loosening in proximal femur replacements using this technique. We examined rates of femoral stem aseptic loosening in proximal femur replacements, functional outcomes, complications, and oncologic outcomes. METHODS: We conducted a retrospective review of 47 patients who underwent proximal femur replacement between 2000 and 2019. Two reviewers evaluated preoperative and postoperative radiographs using the International Society of Limb Salvage scoring system and Barrack criteria for stem loosening. The acetabulum was evaluated according to the criteria of Baker et al. Functional outcomes were assessed using Musculoskeletal Tumor Society (MSTS) score and Toronto Extremity Salvage Score. The mean follow-up was 44 months. RESULTS: The mean International Society of Limb Salvage scores for the 2 reviewers were 86% ± 6% and 84% ± 6%. The first reviewer graded femoral stem loosening as "possibly loose" in 2 patients, one of whom was graded as possibly loose by the second reviewer. The 2 reviewers found no acetabular erosion in 16 (70%) and 15 (65.4%) patients, respectively. The mean Musculoskeletal Tumor Society score and Toronto Extremity Salvage Score at last follow-up were 61% and 72%, respectively. Twenty complications occurred in 13 patients, and 5 patients experienced local recurrence. CONCLUSION: Despite complications, we showed favorable femoral component survival rates. Cementing the proximal femur prosthesis with tight canal fit and thin cement mantle is a viable option for the short and medium term. LEVEL OF EVIDENCE: III.

Wine and Cardiovascular Health: A Comprehensive Review.

Alcoholic beverages have been consumed for thousands of years, attracting great human interest for social, personal, and religious occasions. In addition, they have long been debated to confer cardioprotective benefits. The French Paradox is an observation of a low prevalence of ischemic heart disease, with high intakes of saturated fat, a phenomenon accredited to the consumption of red wine. Although many epidemiological investigations have supported this view, others have attributed it to beer or spirits, with many suggesting that the drink type is not important. Although excessive consumption of alcoholic beverages is commonly regarded to be detrimental to cardiovascular health, there is a debate as to whether light-to-moderate intake is cardioprotective. Although there is extensive epidemiological support for this drinking pattern, a consensus has not been reached. On the basis of published work, we describe the composition of wine and the effects of constituent polyphenols on chronic cardiovascular diseases.

Long-term results of revision total hip arthroplasty with a cemented femoral component.

INTRODUCTION: In revision total hip arthroplasty (THA), the cancellous bone is normally completely removed out of the femoral canal during stem extraction. This situation is comparable to primary THA following the shape-closed concept, with some authors advocating to remove the metaphyseal cancellous bone to enhance press-fit stability ("French paradox"). The aim of this study was to investigate the long-term outcome, regarding survival and radiological results, of a cemented straight stem when used for revision THA and to compare these results to the results of the same stem in primary THA. MATERIALS AND METHODS: 178 stem revisions performed between 01/1994 and 08/2008 using the Virtec straight stem were included. The cumulative incidence for re-revision was calculated using a competing risk model. Risk factors for re-revision of the stem were analyzed using an absolute risk regression model. Radiographs analyzed for osteolysis, debonding and subsidence had a minimum follow-up of 10 years. RESULTS: The cumulative incidence for re-revision due to aseptic loosening of the stem was 5.5% (95% CI, 2.9-10.2%) at 10 years. Aseptic loosening was associated with younger age, larger defect size and larger stem size. After a minimum 10-year follow-up, osteolysis was seen in 39 of 80 revision THA. Compared to the results in primary THA, the survival in revision THA with the same implant was inferior. CONCLUSIONS: Cemented straight stems used for revision THA showed excellent long-term results regarding survivorship and radiological outcome. This stem therefore offers a valuable and cost-effective option in revision THA.

Red or white wine consumption effect on atherosclerosis in healthy individuals (In Vino Veritas study).

AIMS: Consumption of wine has a protective effect on cardiovascular diseases. Data from prospective, long-term, head-to-head comparisons of effects of different drinks on markers of atherosclerosis have been insufficient. METHODS AND RESULTS: In Vino Veritas (IVV) study is long-term, prospective, multi-centre, randomized trial comparing effects of red and white wine on atherosclerosis. 157 healthy subjects were randomized to white or red wine consumption for one year. We did not find increase in HDL-cholesterol in the whole group (1.66±0.58 vs 1.62±0.49, p=0.180) or difference between both groups (1.60±0.53 vs 1.64±0.46, p=0.634). At 12 months there was reduction of LDL-cholesterol in both groups, but with no difference between the groups (3.37±0.75 vs 3.60±1.10, p=0.134); there was no difference between the groups in total cholesterol, CRP, fasting blood glucose and liver function tests. Both groups had comparable differences from baseline in levels of parameters of oxidative stress. CONCLUSION: We did not find any clinically relevant differences in the lipid profile, CRP, fasting blood glucose and other markers of atherosclerosis, between long-term consumption of red and white wine. Moreover, we were unable to confirm the hypothesis that wine drinking is associated with an elevation of HDL (Tab. 7, Fig. 1, Ref. 30).

Radiographic assessment of distal femur cemented stems in tumor endoprostheses.

BACKGROUND: Distal femoral endoprosthesis (DFE) has become the optimal method of reconstruction in the skeletally mature patients treated for malignant bone tumor. Albeit literature has reported wide range of aseptic loosening in cemented components (6-32%), few authors showed that cement was not detrimental to long-term success of primary distal femoral implants possibly relating to cementing technique. METHODS: A series of consecutive of DFE (MRS and GMRS, Styker Orthopaedics, Mahwah, NJ) was retrospectively reviewed for evidence of loosening on plain radiographs. All prostheses had the standard straight 127-mm stem and a cemented polyethylene tibial component. Cementing technique involved reaming line to line to the selected stem size and cementing without pressurization. Radiographs were assessed by two independent blinded reviewers and scored for radiolucent zones (>1 mm) and graded as not loose, possibly, probable and definite loose. Furthermore, the final reamer/stem diameters, length of resection, tumor type, adjuvant treatment modalities, bushing exchange/revision surgery and infection rate were recorded. RESULTS: There were 70 patients and none were lost to follow-up. The average radiographic follow-up was 7.2 years (58% had f/u >5 years). Examiner A found 89% of femoral components to be "Not Loose" and 11% (n = 6) "Possibly Loose". Examiner B found 96% of femoral components to be "Not Loose" and 4% (n = 2) to be "Possibly Loose". No components scored as probably or definitely loose. Two DFE stems were reported as "Possibly Loose" by both reviewers. No femoral stem required revisions for either loosening, femur fracture or metal failure. Although infection was frequent, there was no septic loosening. CONCLUSION: Despite our study limitations, no radiographic evidence of loosening was found. Cementing distal femur prosthesis with a tight canal fit and with a thin and inconsistent cement mantle appears to be a viable option at short and medium term.

Synthesis and radical scavenging activities of resveratrol analogs.

Highly substituted polyhydroxylated (E)-stilbenes were synthesized by Mizoroki-Heck reactions and tested for their ability to act as radical scavenger. One of the 56 stilbenes included in this study and investigated in DPPH assays gave an SC50 value of 11.0 µM, hence exhibiting an about 9.3 times higher activity than resveratrol. As shown in a photometric SRB assay using mouse NiH 3T3 fibroblasts, this compound is not cytotoxic up to concentrations of <30 µM.

The history, science, and art of wine and the case for health benefits: perspectives of an oenophilic cardiovascular pathologist.

This article stems from the intersection of the author's long-standing interests in science, medicine, pathology and oenology. A discussion is provided of selected aspects of the science of viticulture and wine production as well as qualities of the finished product crafted by the art of the wine maker. The case for health benefits of moderate consumption of wine and other alcoholic beverages also is discussed. Based on the "French paradox," an analysis is presented of the evidence for the special effects of red wine consumption, particularly as part of the Mediterranean diet and lifestyle. A concluding perspective is given in support of wine as a promoter of civility and social engagement.

Is the French Paradox cementing philosophy superior to the standard cementing? A randomized controlled radiostereometric trial and comparative analysis.

AIMS: Highly polished stems with force-closed design have shown satisfactory clinical results despite being related to relatively high early migration. It has been suggested that the minimal thickness of cement mantles surrounding the femoral stem should be 2 mm to 4 mm to avoid aseptic loosening. The line-to-line cementing technique of the femoral stem, designed to achieve stem press-fit, challenges this opinion. We compared the migration of a highly polished stem with force-closed design by standard and line-to-line cementing to investigate whether differences in early migration of the stems occur in a clinical study. METHODS: In this single-blind, randomized controlled, clinical radiostereometric analysis (RSA) study, the migration pattern of the cemented Corail hip stem was compared between line-to-line and standard cementing in 48 arthroplasties. The primary outcome measure was femoral stem migration in terms of rotation and translation around and along with the X-, Y-, and Z- axes measured using model-based RSA at three, 12, and 24 months. A linear mixed-effects model was used for statistical analysis. RESULTS: Results from mixed model analyses revealed a lower mean retroversion for line-to-line (0.72° (95% confidence interval (CI) 0.38° to 1.07°; p < 0.001), but no significant differences in subsidence between the techniques (-0.15 mm (95% CI -0.53 to 0.227; p = 0.429) at 24 months. Radiolucent lines measuring < 2 mm wide were found in three and five arthroplasties cemented by the standard and line-to-line method, respectively. CONCLUSION: The cemented Corail stem with a force-closed design seems to settle earlier and better with the line-to-line cementing method, although for subsidence the difference was not significant. However, the lower rate of migration into retroversion may reduce the wear and cement deformation, contributing to good long-term fixation and implant survival. Cite this article: Bone Joint J 2022;104-B(1):19-26.

Does the line-to-line cementing technique of the femoral stem create an adequate cement mantle?

BACKGROUND: The line-to-line cementing technique is proposed to create a press-fit in the femoral canal, which is contrary to modern cementing techniques. The term 'French paradox' has been used to describe the acceptable results associated with this technique. It has been suggested that the quality of the mantle may not be satisfactory, predisposing to early failure and aseptic loosening. METHODS: The line-to-line cementing technique, where the femoral stem was oversized by 1 size compared to the broach, was compared to the standard cementing technique using corresponding sized broaches and stems, in 6 pairs of human cadaver femora with taper-slip design C-stems. Cement pressure was measured, and cement mantle thickness was analysed. A mixed effects model with random intercepts was used to examine the relationship between thickness of mantle and cementing technique and between pressure and cementing technique. RESULTS: Line-to-line cementing results in significantly higher pressurisation for longer periods of time leading to better interdigitation but a thinner mantle in some areas. CONCLUSIONS: The results of this study describe the in-vitro advantages and disadvantages of the line-to-line cementing technique.

Ex vivo to in vivo extrapolation of syringic acid and ferulic acid as grape juice proxies for endothelium-dependent vasodilation: Redefining vasoprotective resveratrol of the French paradox.

Resveratrol, in wines, has been implicated to be primarily responsible for the French paradox, remaining controversial. Herein, we elucidated the representative vasodilation-increasing polyphenols from concord grape juice (CGJ) using ex vivo-to-in vivo extrapolation (EVIVE). We verified the interference-free antioxidant response of CGJ post-dose supernatant of deproteinated serum (CPSDS, as ex vivo proxy) in isolated aortic rings, and in healthy, and H2O2-treated endothelial cells (H-ECs). Syringic acid and ferulic acid (SF) were detected in CGJ and post-dose rat serum (PRS). In isolated aortic rings and H-ECs, polyphenols alone, or in combination, at doses equivalent to those detected in PRS, quantitatively reflected endothelium-dependent vasodilation of CPSDS, as evidenced by nitric oxide (NO) formation-mediated antioxidation-sensitive activation of Src kinase with subsequent PI3/Akt-dependent phosphorylation of endothelial NO synthase. Using EVIVE, SF closely reflected CGJ in coronary flow-mediated vasodilation. Hence, SF application in precision ethnomedicine may redefine antioxidant-sensitive vasoprotective resveratrol of the French paradox.

Resveratrol and cardiovascular system-the unfulfilled hopes.

INTRODUCTION: Resveratrol is a natural polyphenolic compound with a stilbene structure endowed with multiple health-promoting effects. Among phenolic compounds, resveratrol is assigned a leading role in the health-promoting effects of red wine. METHODS: The aim of the study was to assess the effect of resveratrol on the cardiovascular system in the experimental and clinical studies conducted so far. Moreover, the paper discusses the results of the most recent meta-analyses assessing resveratrol's therapeutic effect on the cardiovascular system in humans. RESULTS: In animal and preclinical studies, resveratrol has demonstrated a wide physiological and biochemical spectrum of activity, including antioxidant, anti-inflammatory, antiplatelet, and anticoagulant activities, which translated into its health-promoting effects on the cardiovascular system. The performed meta-analyses allow to confirm such an impact, however, after the assessment with the use of the SYRCLE's tool, these studies are burdened with a high risk of bias, and the results are not clearly presented. CONCLUSION: Despite numerous articles and clinical studies, the convincing beneficial mechanisms of resveratrol as well as its health-promoting effects in cardiovascular diseases have not been clearly confirmed in humans. Therefore, there is a need for further clinical studies, especially randomized, double-blind, placebo-controlled trials to objectively confirm the possible health-promoting effects of this substance and to determine both the efficacy and safety, and possible therapeutic potential.

The Microbiota-Gut-Brain Axis-Heart Shunt Part II: Prosaic Foods and the Brain-Heart Connection in Alzheimer Disease.

There is a strong cerebrovascular component to brain aging, Alzheimer disease, and vascular dementia. Foods, common drugs, and the polyphenolic compounds contained in wine modulate health both directly and through the gut microbiota. This observation and novel findings centered on nutrition, biochemistry, and metabolism, as well as the newer insights we gain into the microbiota-gut-brain axis, now lead us to propose a shunt to this classic triad, which involves the heart and cerebrovascular systems. The French paradox and prosaic foods, as they relate to the microbiota-gut-brain axis and neurodegenerative diseases, are discussed in this manuscript, which is the second part of a two-part series of concept papers addressing the notion that the microbiota and host liver metabolism all play roles in brain and heart health.

The Microbiota-Gut-Brain Axis Heart Shunt Part I: The French Paradox, Heart Disease and the Microbiota.

It has been well established that a vegetarian and polyphenol-rich diet, including fruits, vegetables, teas, juices, wine, indigestible fiber and whole grains, provide health-promoting phytochemicals and phytonutrients that are beneficial for the heart and brain. What is not well-characterized is the affect these foods have when co-metabolized within our dynamic gut and its colonizing flora. The concept of a heart shunt within the microbiota-gut-brain axis underscores the close association between brain and heart health and the so-called "French paradox" offers clues for understanding neurodegenerative and cerebrovascular diseases. Moreover, oxidation-redox reactions and redox properties of so-called brain and heart-protective foods are underappreciated as to their enhanced or deleterious mechanisms of action. Focusing on prodromal stages, and common mechanisms underlying heart, cerebrovascular and neurodegenerative diseases, we may unmask and understanding the means to better treat these related diseases.

Is cemented revision total hip arthroplasty a reasonable treatment option in an elderly population?

Revision THA is increasingly performed especially in the elderly population. The surgeon's challenge is to provide a solution that supports immediate full weight-bearing, despite poor bone quality. Shape-closed revision stems facilitate that by combining cement fixation with additional press-fit anchoring. The design tolerates varying cement mantle thickness and inconsistent cancellous bone lining of the femoral canal. Following that philosophy, we present our mid-term results using a long version of a cemented Charnley- Kerboull type stem. From 2010 to 2017, 38 long Charnley-Kerboull revision stems (Centris®, Mathys European Orthopaedics, Bettlach, Switzerland) were implanted and followed prospectively. Surgery was performed via a Hardinge approach in supine position with a third generation cementing technique. Patients were mobilized using full-weight bearing as early as possible. Survival was determined for stem revision for aseptic loosening and stem and/or cup revision for any reason. 20 stems had a minimum follow-up (f/u) of 2 years and were included for further radiological analysis. Detailed subsidence analysis as an early predictor for later aseptic loosening was performed using EBRA-FCA software. Further, the presence of osteolysis and cement debonding was evaluated. Mean follow- up was 4 years. No patient was lost to f/u.18 died of causes unrelated to THA. Stem survival was 100%. Survival for any re-operation was 82.2% (two early infections, one soft-tissue debridement, one cup exchange for recurrent dislocations). None of the cases revised for septic loosening showed signs of persistent infection at final f/u. EBRA-FCA revealed two oligosymptomatic cases of subsidence of 5mm and 6mm over a course of 2 and 12 months, respectively, with stable implants thereafter. Neither required revision. There was no development of osteolysis or debonding. The stem provides a reliable early fullweight bearing solution for revision THA with excellent mid-term survival in an elderly population. Even in two cases where subsidence was present, mobility was not impaired and re-revision could be avoided.

Phospholipid packing defects and oxysterols in atherosclerosis: Dietary prevention and the French paradox.

The research literature on atherosclerosis includes findings investigating the atherosclerotic effect of oxysterols, which are the oxidation products of cholesterol; and the literature on oxysterols refers to mechanisms by which oxysterols cause phospholipid packing defects in cell membranes. This review synthesizes these two bodies of research findings to describe how oxysterols cause phospholipid packing defects within the membranes of vascular endothelial cells, potentially increasing cell permeability of low-density lipoprotein cholesterol which may lead to atheroma formation. Exogenous sources of oxysterols are provided by dietary intake of animal-based foods that contain cholesterol oxidation products. This review proposes an explanation for the anti-atherosclerotic effect of plant-based dietary patterns, which is attributed to restriction or avoidance of dietary oxysterol intake from animal-based foods. Furthermore, raw-milk cheeses play an important role in the traditional French diet-low oxysterol content in these unheated foods may contribute to the French paradox, in which reduced coronary heart disease is associated with a diet high in saturated fat and cholesterol.

Biomechanics of a cemented short stem: Standard vs. line-to-line cementation techniques. A biomechanical in-vitro study involving six osteoporotic pairs of human cadaver femurs.

BACKGROUND: Short-stem total hip arthroplasty (THA) potentially offers advantages compared to conventional THA, including sparing bone and soft tissue and being a facilitated and less traumatic implantation. However, the indication is limited to patients with sufficient bone quality. Cemented short-stem THA might provide an alternative to conventional cemented THA. To date, no cemented short stem is available on the market. METHODS: In the present in vitro study, primary stability of a new cemented short stem was evaluated, comparing standard (undersized stem) versus line-to-line (same-sized stem) cementing techniques, using six pairs of human cadaver femurs. Primary stability, including reversible micromotion and irreversible migration, was assessed in a dynamic material-testing machine. Fracture load was tested and fracture pattern analyzed. FINDINGS: Both cementation techniques (standard vs. line-to-line) displayed comparable results with respect to primary stability without any statistical differences (micromotion: 17.5 µm vs. 9.6 µm (p = 0.063); migration: 9.5 µm vs. 38.2 µm (p = 0.188)). Regarding fracture load, again, no difference was observed (3670 N vs. 3687 N (p = 0.063)). In all cases, proximal fractures of Vancouver type B3 occurred. INTERPRETATION: The present in vitro study demonstrates that the line-to-line cementation technique, which is favourable regarding the philosophy of short stem THA, can be further pursued in the course of the development of a cemented short stem. Further investigations should address how well the cemented short stem compares to well-established cemented straight-stem designs.

The Oxygen Paradox, the French Paradox, and age-related diseases.

A paradox is a seemingly absurd or impossible concept, proposition, or theory that is often difficult to understand or explain, sometimes apparently self-contradictory, and yet ultimately correct or true. How is it possible, for example, that oxygen "a toxic environmental poison" could be also indispensable for life (Beckman and Ames Physiol Rev 78(2):547-81, 1998; Stadtman and Berlett Chem Res Toxicol 10(5):485-94, 1997)?: the so-called Oxygen Paradox (Davies and Ursini 1995; Davies Biochem Soc Symp 61:1-31, 1995). How can French people apparently disregard the rule that high dietary intakes of cholesterol and saturated fats (e.g., cheese and paté) will result in an early death from cardiovascular diseases (Renaud and de Lorgeril Lancet 339(8808):1523-6, 1992; Catalgol et al. Front Pharmacol 3:141, 2012; Eisenberg et al. Nat Med 22(12):1428-1438, 2016)?: the so-called, French Paradox. Doubtless, the truth is not a duality and epistemological bias probably generates apparently self-contradictory conclusions. Perhaps nowhere in biology are there so many apparently contradictory views, and even experimental results, affecting human physiology and pathology as in the fields of free radicals and oxidative stress, antioxidants, foods and drinks, and dietary recommendations; this is particularly true when issues such as disease-susceptibility or avoidance, "healthspan," "lifespan," and ageing are involved. Consider, for example, the apparently paradoxical observation that treatment with low doses of a substance that is toxic at high concentrations may actually induce transient adaptations that protect against a subsequent exposure to the same (or similar) toxin. This particular paradox is now mechanistically explained as "Adaptive Homeostasis" (Davies Mol Asp Med 49:1-7, 2016; Pomatto et al. 2017a; Lomeli et al. Clin Sci (Lond) 131(21):2573-2599, 2017; Pomatto and Davies 2017); the non-damaging process by which an apparent toxicant can activate biological signal transduction pathways to increase expression of protective genes, by mechanisms that are completely different from those by which the same agent induces toxicity at high concentrations. In this review, we explore the influences and effects of paradoxes such as the Oxygen Paradox and the French Paradox on the etiology, progression, and outcomes of many of the major human age-related diseases, as well as the basic biological phenomenon of ageing itself.

Dairy products and the French paradox: Could alkaline phosphatases play a role?

The French paradox - high saturated fat consumption but low incidence of cardiovascular disease (CVD) and mortality - is still unresolved and continues to be a matter of debate and controversy. Recently, it was hypothesised that the high consumption of dairy products, and especially cheese by the French population might contribute to the explanation of the French paradox, in addition to the "(red) wine" hypothesis. Most notably this would involve milk bioactive peptides and biomolecules from cheese moulds. Here, we support the "dairy products" hypothesis further by proposing the "alkaline phosphatase" hypothesis. First, intestinal alkaline phosphatase (IAP), a potent endogenous anti-inflammatory enzyme, is directly stimulated by various components of milk (e.g. casein, calcium, lactose and even fat). This enzyme dephosphorylates and thus detoxifies pro-inflammatory microbial components like lipopolysaccharide, making them unable to trigger inflammatory responses and generate chronic low-grade inflammation leading to insulin resistance, glucose intolerance, type-2 diabetes, metabolic syndrome and obesity, known risk factors for CVD. Various vitamins present in high amounts in dairy products (e.g. vitamins A and D; methyl-donors: folate and vitamin B12), and also fermentation products such as butyrate and propionate found e.g. in cheese, all stimulate intestinal alkaline phosphatase. Second, moulded cheeses like Roquefort contain fungi producing an alkaline phosphatase. Third, milk itself contains a tissue nonspecific isoform of alkaline phosphatase that may function as IAP. Milk alkaline phosphatase is present in raw milk and dairy products increasingly consumed in France. It is deactivated by pasteurization but it can partially reactivate after thermal treatment. Experimental consolidation of the "alkaline phosphatase" hypothesis will require further work including: systematic alkaline phosphatase activity measurements in dairy products, live dairy ferments and intestine of model animals. Furthermore, stool residual IAP, a possible early marker of diabetes, should be assayed in human cohorts. If confirmed, this "alkaline phosphatase" hypothesis will highlight the protective effects of milk alkaline phosphatase and promote the consumption of (microbiologically safe) raw milk and dairy products. Microorganisms secreting alkaline phosphatases may be privileged as ferments in dairy products.