Vitamin A Educates T-Cells, Joins Forces With Vitamin D Against Liver Cancer. Milk Better Than Sugary Electrolyte Solutions for Rehydration? Helicobactor Pylori: Probiotics from Breast Milk & Feces Better Than Amoxicillin!

Lactobacilli are hip, vitamin A is not - at the SuppVersity you still get news on both

1kg! That's the amount of weight you could probably lose if you rid yourself of all the microbes in your gut - from the weight of the bacteria alone, of course. Whether this would be a good idea or not, is however very questionable. On the one hand, we do have the still not fully understood studies on obesity-resistant germ free mice and an accumulating amount of evidence that having the "wrong" bacteria in the gut is at least associated with an increased obesity risk (Blaut. 2013). On the other hand, however, we are seeing new studies on the various benefits of having the "right" gut microbiome being published on an almost daily basis. So what?

Before we take a closer look at a definite benefit of having the "right" gut bacteria, though, let's start out with another likewise gut-related news item on the role of retinoic acid in T-cell education. In a way it's funny, it starts right where the bacteria reside, could have immune-modulatory effects that are way more pronounced and far reaching than probiotics and is still hardly discussed.

Vitamin A is of critical importance to (intestinal) T-cell education

If you have ever asked yourself how the immune cells in your body know what they are supposed to do, Catharine Ross' latest paper that was published in the American Journal of Clinical Nutrition and is based on a short talk the researcher from the Department of Nutritional Sciences at the Pennsylvania State University held at a conference earlier this year may provide at least some additional insides into the role a still way underrated molecule plays in this "T cell education" (Ross. 2013): Vitamin A!

Figure 1: Model of T cell differentiation, from uncommitted naive T cells into different T cell subsets that produce different cytokines and thus promote different functional activities (adapted from Ross. 2013)

As you can see in figure 1, retinoic acid does not simply promote the differentiation of regulatory T cells, which help to suppress inflammatory reactions, it also plays a significant role in normal mucosal immunity (in the gut, the airways and elsewhere) by modulating T cell activation and regulating cell trafficking. Moreover, vitamin A promotes antibody responses to T cell–dependent antigens. Needless to say that

"[...] in a state of vitamin A deficiency, inflammatory T cell reactions may be inadequately opposed and therefore become dominant [...] Although data from human studies are still needed, the framework now developed from studies in mice and rat models suggests that adequate vitamin A status, [...] is  important for maintaining a proper balance of well-regulated T cell functions and for preventing excessive or prolonged inflammatory reactions." (Ross. 2013).

Discovery a beta carotene derived vitamin A receptor blocker is only one of a couple of intriguing findings wrt to vitamin A.

One thing that sticks out from the complex interactions (see figure 1), really is the way by which the interaction of vitamin A with the T-cells in the gut crucially determine the efficiency of the 'fist line defenses' and their downstream effects on the whole organism. It is by no means co-incidental that diarrhea is rampant in areas of the "third world", where a large amount of the population is vitamin A deficient (Beaton. 1994). And in fact studies have shown consitently that

"RA is essential for 'imprinting' gut-homing specificity on T cells activated by intestinal DCs [dendritic cells] and suggested that MLN DCs are a source of RA that drives T cell differentiation toward the gut-homing phenotype" (Ross. 2013)

Moreover, oral tolerance to foreign antigens and thus an allergy free live requires a form of immune suppression, which can be proffered or hampered by sufficient and insufficient vitamin A intakes. In that, the exact effects of vitamin A will depend on the cytokine milieu the T-cells are exposed to. Examples are...

• an exaggerated IL-17 response with vitamin A deficiency, on the one hand, and
  
• an increase of the inflammatory response due to high vitamin A in an IL-15 environment 

Based on these observations, Ross rightly points out that "when RA is used for therapeutic purposes, it should be used cautiously in subjects with various inflammatory bowel conditions and sensitivities to dietary antigens." (Ross. 2013) People with gluten intolerance, celiac and other allergic reactions, for example would probably be better off avoiding the consumption of any form of supplemental vitamin A (on top of what's in their regular diet). Someone with high IL-17 and IL-6 levels as they have been observed in non-celiac inflammatory bowel disease, type 1 diabetes, multiple sclerosis and rheumatoid arthritis, on the other hand, could actually benefit from vitamin A's (especially ATRA) presence during activation of CD4⁺ T cells, because it will - even in the presence of IL-6 - "favor the development of the a Treg lineage at the expense of T cells secreting IL-17" and could thus help reduce chronic inflammation and keep autoimmune reactions at bay (Schambach. 2007; also Ramgolam. 2010).

More news

• 

  Figure 2: Who cares about cell viability, the survival time (in days) matters

  Combination therapy with vitamin A and a vitamin D (not D3, but calcitriol) analog EB1089 kills liver cancer cells. And it does so more effectively than any of the two molecules alone. That's the actually unsurprising result of a study that has been conducted at the Beijing Army General Hospital in China. The researchers injected nude mice with molecules that made them develop hepatocellular cancer. Afterwards, the rodents received either 10 μmol/L retinoic acid (vitamin A), 10 nmol/L EB1089 or both as a combination treatment.
  
  Compared to vitamin A or the calcitriol analog alone, the combination treatmend resulted in a significanlty higher reduction of the viability of hepatocellular cancer cells. Based on TUNEL analysis, Zhang et al. did also establish that individual cancer cells had a higher apoptotic ratio in the combined drug group than in the groups for which the drugs were used separately. Most importantly, however, the tumor weight was decreased and the mice on the combination treatment lived significantly longer (see figure 2; Zhang. 2013)

• 

  In the same publication, Pritchett and Pritchett recommend 1.0-1.5ml / kg body weight per hour of chocolate milk as the optimal post-workout drink to be consumed in the 2 h after a workout.

  Skimmed milk, the ideal post-workout rehydration formula? According to L James' paper in Lamprecht's compendium Acute Topics in Sport Nutrition, milk is a way better choice then the standard sugar + electrolyte rehydration formulas. Interestingly this is not due to the minerals in the milk, or the sugar, but, as James argues, a direct consequence of the milk proteins, which help restore "fluid balance after exercise-induced dehydration to a greater extent than a carbohydrate-electrolyte sports drink." As James points out it will yet have to be elucidated, whether the simple addition of whey protein to a standard sugar + electrolyte formula would exert similar effects (James. 2013).
• Probiotics to kill Helicobacter Pylori? While not every bacteria stands a chance against the nasty gut bug H. Pylori, certain Lactobacillus spp. strains obviously do. At least, if the results of a recent in-vitro + in vivo rodent study by Pei-Shan Hsieh can be replicated in human studies.

  

  Figure 3: Urease activity in H. pylpori after co-incubation with the specific probiotic and resulting bacteriostatic ratio (100% = bacteria free; data adapted from Hsieh. 2013)

  Lactobacillus acidophilus TYCA08, L. acidophilus TYCA15, L. johnsonii MH-68, and L. salivarius subsp. salicinius AP-32 were the most effective strains the researchers from National Chung Hsing University in Taichung, Taiwan, analyzed. And believe it or not, the latter of these, i.e. L. johnsonii MH-68, and L. salivarius subsp. salicinius AP-32, both of which are  by the way found in feces, were even minimally more potent effective than Amoxicillin, a moderate-spectrum, bacteriolytic, β-lactam antibiotic used to treat bacterial infections. L. acidophilus TYCA15, however, steals the show. This probiotic that occurs naturally in breast milk reduced the urease activity of H. Pylori by -97.1% (see figure 3).
  
  In the consecutive rodent study, Hseieh et al. did yet still use 10⁹ CFU/mL of either AP-32 alone, MH-68 alone, or an equal mix of cultures of the two strains and both, "either alone or as a mixture in powder form were effective in reducing H. pylori load in gastric mucosa and help in reducing gastric inflammation and in regulation of gastric acid production." (Hsieh. 2013)

Thats it for today and for this weekend. As mentioned yesterday, there was simply not enough time to do the necessary research for the follow up to the Athlete Triad Series, so that this will have to wait. So don't dig an even deeper whole in the mean time. Maybe you want to do some of the psychomotor tests mentioned in yesterday's news, and check whether you are already overtrained!? How steady are your hands, for example? And whatever the result may be, don't forget to enjoy the rest of the weekend!

References:

• Beaton GH, Martorell R, Aronson KA, Edmonston B. McCabe, G, Ross, AC, Harvey, B. Vitamin A supplementation and child morbidity and mortality in developing countries. Food Nutr Bull 1994;15(4): 282–9.
• Blaut M, Klaus S. Intestinal microbiota and obesity. Handb Exp Pharmacol. 2013;(209):251-73.
• Hsieh PS, Tsai YC, Chen YC, Teh SF, Ou CM, King VA. Eradication of Helicobacter pylori Infection by the Probiotic Strains Lactobacillus johnsonii MH-68 and L. salivarius ssp. salicinius AP-32. Helicobacter. 2013 Dec;17(6):466-77.
• James L. Milk Protein and the Restoration of Fluid Balance after Exercise. In Lamprecht M (ed): Acute Topics in Sport Nutrition. Med Sport Sci. Basel, Karger, 2013, vol 59, pp 120–126. 
• Pritchett K, Pritchett R. Chocolate Milk: A Post-Exercise Recovery Beverage for Endurance Sports. In Lamprecht M (ed): Acute Topics in Sport Nutrition. Med Sport Sci. Basel, Karger, 2013, vol 59, pp 127–134.
• Ramgolam VS, Markovic-Plese S. Interferon-beta inhibits Th17 cell differentiation in patients with multiple sclerosis. Endocr Metab Immune Disord Drug Targets. 2010 Jun;10(2):161-7.
• Ross AC. Vitamin A and retinoic acid in T cell-related immunity. Am J Clin Nutr. 2013 Oct 10.  
• Schambach F, Schupp M, Lazar MA, Reiner SL. Activation of retinoic acid receptor-alpha favours regulatory T cell induction at the expense of IL-17-secreting T helper cell differentiation. Eur J Immunol. 2007 Sep;37(9):2396-9. 
• Zhang J, Zhang H, Zhang X, Yu Z. Synergistic effect of retinoic acid and vitamin D analog EB1089-induced apoptosis of hepatocellular cancer cells. Cytotechnology. 2013 Oct 16.

Fat Advantage: 61% Lower Rates of Metabolic Syndrome in High Fat, 101% Higher Rates in Low Fat Dairy Lovers

"Got milk" is not the question health conscious supermen and -women should pose. "Got full fat milk, fermented dairy and cheese" is the line to remember (the original image was part of the "Got Milk Campaign")

While diet fads come and go, the advice the wise (not seldom obese or otherwise sick) experts on the boards and panels of our well-meaning governments is calling "dietary recommendations" is about as resistant to reform as the dreaded MSRA strains are to the antibiotics doctors are throwing at you whenever you sneeze. Against that background the recent trend we are seeing with respect to an increase in the recommended amount of dietary protein does almost amount to a quantum leap; a leap with a significant caveat, however. A fat caveat, so to say:

"A healthy diet includes [...] lean meats, poultry, fish, beans and fat-free or low-fat dairy products" (NIH. 2013).

Luckily, you as a SuppVersity reader do not have to rely on the NHI's thwarted interpretations of the latest research they claim to use, when they are "turning discovery into health" (no joke, this is a literal citation from the footer of the NHI website!), but can compare it to my thwarted interpretations of the latest research and cherry picked data ;-)

Cherry pick of the day: Longitudinal large scale study on dairy intake and metabolic health

 For Today, this means that you get to enjoy the latest results of a large scale observational study from the University of Sydney that's based on datasets from the Blue Mountains Eye Study (BMES) a population-based cohort study of common eye diseases and other health conditions in residents aged 49 years and over in the Blue Mountains area, west of Sydney. A longitudinal study the baseline information was obtained in 1992/1994 from  and complemented by follow-up ten years later.

The data sets included food frequency questionnaires, as well as anthropometric and biochemical assessments all of which were included in the present analysis of the association betweenn dairy consumption with the ten-year incidence of Metabolic syndrome (MetSyn) and type 2 diabetes. What's so special about this dataset, is that the food questionnaires were actually detailed enough to assess the effects of full- and low-fat dairy, separately - a very important advantage, as a cursory glance at the data in figure 1 reveals.

Figure 1: Odds ratios (95% confidence intervals) of incident metabolic syndrome according to quartiles of reduced/low fat,
regular fat and total dairy product intake (data based on Louie. 2013; adjustments for age and sex (basic model), smoking status, physical activity (metabolic equivalents), dietary glycemic load, fibre from vegetables, total energy intake and family history of type 2 diabetes (model 1) and calcium (model 2))

While the standard analysis for total dairy consumption (figure 1, left) yielded neither conclusive, nor statistically significant results (the p-values for the different models can be found in the upper right corner of the respective graphs). The categorization into low- and high fat dairy and the adjustments for age and sex (basic model), smoking status, physical activity (metabolic equivalents), dietary glycemic load, fibre from vegetables, total energy intake and family history of type 2 diabetes (model 1) and calcium (model 2) yields very clear and, after adjustment for calcium intake, pretty unflattering result the formulators of the afore mentioned "dietary recommendations" will probably file in their already bristling "statistical outliers"-folder:

• after adjustment for calcium intake subject in quartiles 2 / 3 / 4 of low-fat dairy are 50% / 145% / 101% more likely to be struck by metabolic syndrome, than those in the lowest quartile of low fat dairy intake (p = 0.043), while
• subjects in the highest quartile of full-fat dairy intake are - depending on the adjustments made -  48% / 59% / 61% less likely (base model / model 1 / model 2) to suffer frommetabolic syndrome, than those in the lowest quartile of high fat dairy intake (p-values:  0.018 / 0.004 / 0.004)

Yet while the scientists are well aware, that these results stand in stark contrast to the initially cited dietary recommendations, is it not this contrast that surprises them, but rather the fact that a similar significant benefit was not observed for type II diabetes, which is, after all, one of the hallmark features of the rather loosely defined triad of obesity, insulin resistance and cardiovascular disease(s), we usually refer to as 'metabaolic syndrome':

"Due to its higher saturated fat content, regular fat/high fat dairy products were previously believed to increase the risk of type 2 diabetes as a high saturated fat intake is associated with insulin resistance . However, cohort studies and a meta-analysis now suggest otherwise, with higher regular fat/high fat dairy consumption being considered mostly neutral or protective for type 2 diabetes. The results of the present study are consistent with these findings that higher regular fat dairy consumption may be protective of MetSyn and type 2 diabetes. The potential harmful effects of higher saturated fat from regular fat dairy products may have been offset by the protective components of regular fat dairy such as trans-palmitoleate, a fatty acid nearly unique to ruminant foods. Circulating level of trans-palmitoleate was shown to be significantly associated with reduced risk of type 2 diabetes (Q5 vs Q1: 62% reduced risk, p-trend < 0.001). Moreover, the protective effect of trans-palmitoleate may be exerted via the suppression of hepatic fat synthesis, where the latter was strongly associated with insulin resistance." (Louie. 2013; my emphases)

In view of these mechanism, it is all the more surprising that the study at hand and many previous studies didn't find any significant correlations between (regular fat) dairy intake and type II diabetes.

Reduction in metabolic risk, but no effect on type diabetes? Hold on...

Wolverine could be the only face of the "Got Milk" campaign who does not have to care about potential negative health effects of homogenized milk.

And upon a cursory read of the latest literature it does in fact seem as if "null findings" like this, were nothing special. Only recently by Sluijs et al. who had analyzed datasets from a nested case-cohort within 8 European countries of the European Prospective Investigation into Cancer and Nutrition Study (n = 340,234; 3.99 million person-years of follow-up) includind a random subcohort (n = 16,835) and incident diabetes cases (n = 12,403; cf. Slujis. 2013):

"This large prospective study found no association between total dairy product intake and diabetes risk. An inverse association of cheese intake and combined fermented dairy product intake with diabetes is suggested, which merits further study." (Sluijs. 2013)

If we do yet take a closer look at the actual results the actually not so surprising truth is that there was a statistically significant inverse association with diabetes for cheese (p = 0.01) and fermented dairy (p = 0.02).

An association that suggests a 12% reduction in diabetes risk in those study participants who consumed the most cheese and fermented dairy (cheese, yogurt, and thick fermented milk)

And since you all know your real foods, I guess I don't have to tell you that despite the fact that there are low fat varieties of cheese yogurts and other fermented milk products, 90% of them contain way more than the 1.5% let alone 0.1% fat the allegedly healthy low fat "milk" is boasting of. Mere coincidence? I don't think so. Reason to assume that low-fat milk will make you sick? No, but certainly not an argument to avoid the full-fat variety simply because it contains fat (which is the only argument the average dietitian has to favor low- over full-fat dairy products).

Mutant Milk!? New Research Fuels the Flames on Hushed Up Concerns About Ill Health Effects of Homogenized Milk 

Ask Dr. Andro: Are Colostrum and Milk Products in General Healthy Muscle Builders, a Waste of Money or Toxic Waste?

All about milk: Browse past news and articles at the SuppVersity

^ Suggested reads

Additional recent dairy science:Similar beneficial findings for all-cause mortality and fermented dairy (yet inconclusive results for CVD and diabetes) come from the recently published Whitehall II study (4526 subjects,72 % men, mean age 56 years; Soedamah-Muthu. 2013) and for dairy intake during adolescents and diabetes (-38% risk reduction for 2 servings per day or more) from a reanalysis of somewhat questionable data (who remembers exactly how much dairy he had during his adolescence?) from the Nurses' Health Study II cohort that comprises 37,038 women who completed a food-frequency questionnaire about their diet during high school were followed from the time of return of the questionnaire in 1998-2005 (Malik. 2013).


References:

• Louie JC, Flood VM, Rangan AM, Burlutsky G, Gill TP, Gopinath B, Mitchell P. Higher regular fat dairy consumption is associated with lower incidence of metabolic syndrome but not type 2 diabetes. Nutr Metab Cardiovasc Dis. 2013 Sep 26. pii: S0939-4753(12)00193-7. 
• Malik VS, Sun Q, van Dam RM, Rimm EB, Willett WC, Rosner B, Hu FB. Adolescent dairy product consumption and risk of type 2 diabetes in middle-aged women. Am J Clin Nutr. 2011 Sep;94(3):854-61.
• NIH. Health in the News: Love Your Heart. February 2013. < http://newsinhealth.nih.gov/issue/feb2013/feature1 > retreived Oct 02, 2013.
• Soedamah-Muthu SS, Masset G, Verberne L, Geleijnse JM, Brunner EJ. Consumption of dairy products and associations with incident diabetes, CHD and mortality in the Whitehall II study. Br J Nutr. 2013 Jun 7:1-9.
• Sluijs I, Forouhi NG, Beulens JW, van der Schouw YT, Agnoli C, Arriola L, Balkau B, Barricarte A, Boeing H, Bueno-de-Mesquita HB, Clavel-Chapelon F, Crowe FL, de Lauzon-Guillain B, Drogan D, Franks PW, Gavrila D, Gonzalez C, Halkjaer J, Kaaks R, Moskal A, Nilsson P, Overvad K, Palli D, Panico S, Quirós JR, Ricceri F, Rinaldi S, Rolandsson O, Sacerdote C, Sánchez MJ, Slimani N, Spijkerman AM, Teucher B, Tjonneland A, Tormo MJ, Tumino R, van der A DL, Sharp SJ, Langenberg C, Feskens EJ, Riboli E, Wareham NJ; InterAct Consortium. The amount and type of dairy product intake and incident type 2 diabetes: results from the EPIC-InterAct Study. Am J Clin Nutr. 2013 Aug;96(2):382-90.

Mutant Milk!? New Research Fuels the Flames on Hushed Up Concerns About Ill Health Effects of Homogenized Milk

Image 1: Wolverine could be the only face of the "Got Milk" campaign who does not have to care about potential negative health effects of homogenized milk.

In view of the fact that even the Wikipedia article on milk mentions the long-touted hypothesis that the release of the  membrane bound (bovine) xanthine oxidase during the homogenization process and it's potential to generate reactive oxygen specimen could pose a serious health risk, it's quite funny that none of the multitude of papers on the pro- or anti-atheriogenic effects of milk ever mentions mentions the issue of homogenization.

Now even if we discard the potential negative effects of BXO, the results of a recently published paper from the Center of Specialized Nutrition in the Netherlands would still suggest that milk does at least lose some of it's beneficial health effects in the course of the homogenization process (Oosting. 2013).

Large and fluffy or small? That does ring a bell, doesn't it? 

In their experiments the Dutch scientists fed mice infant formulas with either small or large phospholipid coated lipid droplets. Probably to the utmost satisfaction of Danone, the producer of the large lipid droplet formula (Nuturis) and sponsor of the study, the mice who received the regular formula with small lipid droplets were fatter and had compromised lipid and blood glucose levels (see figure 1), as well as pathologically increased leptin levels (not shown in figure 1).

Figure 1: It may remind you of comparing apples and oranges, but let's be honest, if it were not for the disruption of the large fat globules during the homogenization process, similarly large phospholipids as those Danone plans to unleash onto our children would be present in milk, anyway.

Irrespective of the funding and product pimping, the results of this study could have major implications that reach way beyond infant formulas and parenteral nutrition. After all, homogenized milk is common used in all sorts of milk based or milk-containing products. It's shelf stable and above all highly standardized and easily processable by the dairy and food industry, who are still spending truckloads of money to find means to further reduce the unwanted clumping that's so characteristic for the naturally occurring large fat molecules most of the end-consumer don't want to float on top of their heated milk either.

So, if the bovine xanthine oxidase that's released during the homogenization process does not, as Ho & Clifford and other researchers argued in the late 1970s (Ho. 1977), pose a risk for heart disease, what about the structural changes in the lipid fraction of milk? Do we know anything about these at all and could they be the underlying cause of the increase in allergies, diabetes risk that have never been convincingly attributed to milk consumption in general or whole milk consumption in particular? Did we focus to much on the quantity and type of fat in the milk and overlooked its structural organization?

Though shalt not fix something that ain't broken!

In a 2007 review of the literature on the potential impact homogenized milk could have on our health, Mikalski discusses exactly this question: What's the physiological consequence of the physical "rupture of fat globules" which occurs during the heating and homogenization process and "creates a new interface" on the membrane of the fat globules so that "other surface active components" (Mikalski. 2007) will more or less randomly adsorb to the remnants and form a new structurally different membrane.

Figure 2: After the homogenization process took place none of the original functional large fat globules is left, smaller ruptured globules have taken their place and are used by other molecules as a "Trojan horse" (left), distribution of milk fat globule sizes in different types of whole milk - open circles - raw whole milk, full circles - whole milk homogenized at 5MPa, open squares - whole milk homogenized at 10 MPa, full squares - whole milk homogenized at 50MPa (partly adapted from Mikalski. 2007)

Unfortunately, the #1 compound that will bind to the now the disrupted surface structures of the molecules in the homogenized monster milk are casein micelles (Zahar. 1996). Yep, exactly those molecules, of which some scientists, though most of them discard the hypothesis that homogenized milk is not at least as good for you as regular milk, still speculate that they could be responsible for many if not all of the aforementioned negative health effects of milk (Kohno. 1994; Laugesen. 2003; Tailford. 2003).

Homogenized, fat reduced zombie milk?

Figure 3: Distribution of milk lipids in globule core, membrane and skim phase (top, based on Michalski. 2007) and electron micrographs at 15× and 100× augmentations of (A) raw, (B) pasteurised, (C) homogenised–pasteurised, and ultra-high-pressure homogenised milk samples at (D) 100 MPa (Zamora. 2013)

That the process of homogenization will also affect the normal distribution of tri- and diacylglycerols, which are necessarily released from the core of the ruptured fat molecules (figure 3, top - blue) and modify the intricate phospholipid structure of the membrane (figure 3, top - red) should be as obvious as the fact that those tri- and diacylglycerols, phospholipids, cerebrosides and gangliosides are suddenly part of the skim fraction are easily lost during further processing (such as the removal of fat) and will have different physical attributes, physiological effects, digestive properties and absorption kinetics (cf. Berton. 2013).

The degree of homogenization increases according to the pressure that's used to force the the hot milk between valve needle and seat of the homogenization machine, so that  the aforementioned effects are particularly pronounced in the high-pressure homogenized milk (also "ultra-homogenized" milk). Accordingly even the last few "unwanted" (by the food industry) larger, intact fat globules that are left in the regular homogenized milk (figure 3, C) break apart.

What used to be a huge container-like fat molecule in the raw milk (figure 3, A), survived the pasteurization process relatively unharmed (figure 3, B) is now, after it has been pressed with 100MPa through the valve of the homogenization machine, nothing but a heap of very shelf-stable and non-clumping, highly convenient debris (figure 3, D) - awesome, right?

Bottom line: Aside from the disgusting taste of what we here in Germany call "H-Milch" ("h" as in "haltbar", which denotes the longer shelf-life) the structural changes and the potentially problematic downstream effects of the homogenization process, such as

Image 2: Assuming that the plastic canister the girl on the right holds in her hands contains homogenized milk, it may in fact be better for the girl on the left, if it was fat free :-o After all, when the homogenized whole milk is further processed into 0.2% = no fat milk ~95% of the previously created mutant fat molecules will be removed ;-)

• a rise in potentially artherosclerotic free bovine xanthine oxidase, which would otherwise be "locked" in the the intact milk fat globule membrane (MFGM),
• the formation of new lipid layers from casein and other milk components and milk fat globule membrane fragments with potentially allergenic, and inflammatory properties,
• a decrease in curd formation / stability, an increase proteolysis and lipolysis (=digestion of the proteins and fats) and the subsequent increase in nutrient absorption and speed in the gastrointestinal tract with its potentially detrimental downstream effects on blood lipids, and
• the increased absorption of casein molecules and the loss of the beneficial health affects such as the anti-viral, antimicrobial, anabolic and gut protective effects that have been ascribed to the natural MFGM structure of milk

should be reason enough not to make the most convenient, but the most natural choice - and that irrespective of whether the milk is for a toddler, a child, a teen or an adult... and by the way, the changes the fat molecules in the milk are undergoing and the subsequent "mutant" protein + fat fragment structures they are forming make the otherwise nonsensical advice to use "low" or better "no-fat dairy" actually appear quite sensible.

Apropos "high fat dairy", did I mention that the "bad high fat cheese" is not just almost always made from regular, non-homogenized milk (which is hard to get, these days, as even the cooled milk is routinely homogenized, so make sure to check the label), but that its consumption is also associated with a decreased risk of developing metabolic syndrome (Høstmark. 2011)? No... well, than that's even more food for thought ;-)

References

• Berton A,Rouvellaca S, Robertd B, Rousseaud F, Lopez C. Effect of the size and interface composition of milkfatglobules on their in vitro digestion by the human pancreatic lipase: Native versus homogenized milk fat globules. Food Hydrocolloids. 2013; 29:1, 123–134. 
• Ho C, Clifford A Bovine milk xanthine oxidase, blood lipids and coronary plaques in rabbits.J Nutr. 1977; 107, 758–766
• Høstmark AT, Tomten SE. The Oslo health study: cheese intake was negatively associated with the metabolic syndrome. J Am Coll Nutr. 2011 Jun;30(3):182-90.
• Kohno Y, Honma K, Saito K, Shimojo N, Tsunoo H, Kaminogawa S, Niimi H. Preferential recognition of primary protein structures of alpha-casein by IgG and IgE antibodies of patients with milk allergy. Ann Allergy. 1994 Nov;73(5):419-22.
• Laugesen M, Elliott R. Ischaemic heart disease, Type 1 diabetes, and cow milk A1 beta-casein. N Z Med J. 2003 Jan 24;116(1168):U295.
• Michalski MC. On the supposed influence of milk homogenization on the risk of CVD, diabetes and allergy. Br J Nutr. 2007 Apr;97(4):598-610.
• Oosting A, Kegler D, Wopereis HJ, Teller IC, van de Heijning BJ, Verkade HJ, van der Beek EM. Size and Phospholipid Coating of Lipid Droplets in the Diet of Young Mice Modify Body Fat Accumulation in Adulthood. Pediatr Res. 2013 Jul 31.
• Tailford KA, Berry CL, Thomas AC, Campbell JH. A casein variant in cow's milk is atherogenic. Atherosclerosis. 2003 Sep;170(1):13-9.
• Zahar M, Smith D- Adsorption of proteins at the lipid-serum interface in milk systems with various lipids. Int Dairy J. 1996: 6, 697–708.
• Zamora A, Ferragut V, Guamis B, Trujillo AJ. Corresponding author contact informationChanges in the surface protein of the fat globules during ultra-high pressure homogenisation and conventional treatments of milk. Food Hydrocolloids. 2013; 21:1, 135–143.

Are Camels the Better Cows? Cancer, Heart Disease, High LDL and Triglycerides, Diabetes, High Blood Pressure, Allergies, Viral and Bacterial Infections and Trace Mineral Deficiencies, Camel Milk Prevents or Fixes Them All!

Image 1: To the average inhabitant of the Western hemisphere camels are probably not the most beautiful animals under the sun; but hey, cows aren't either, hah?

When muscle-heads think of dairy, they think of whey, they think of casein, they think of cottage cheese... but I bet few of them will think of camels! Even if you just went by the mere amino acid composition (see. figure 2 at the end of the article), of which you, as an educated SuppVersity student should by now be aware that it does not give you the 'whole picture', as far as the biological effects of a given protein and peptide containing foodstuff is concerned, it appears that camel milk would at least make an excellent alternative for cows milk, in case global warming is progressing and Europe and the US turn into desert wastelands... but all jokes aside, muscle is not everything and I bet that after reading this article you will be interested to register for the US' first official camel milking seminar *rofl*

7+1 reasons you may want to slaughter your grass fed cows and replace them with camels

While the idea of drinking the milk of an ugly desert ship may appear hilarious at first, I guess my compilation of purported and scientifically established benefits of camels milk will have you reconsider if the Sheikh Hamdan bin Mohammed bin Rashed Al-Maktoum, Crown Prince of Dubai, may not have made a very good investment, when he spent $16.5 million dirham ($4.5 million USD) on the winner of a 2008 beauty pageant in the United Arab Emirates’ capital city of Abu Dhabi (FYI, the guy in image 1 is not the Sheikh, just tom make sure I don't get sued, here ;-):

Image 2 (DrCate.com): Homogenization makes milk more convenient, but it disrupts the natural structure of the fat globules and releases the otherwise bound xanthine oxidase of which scientists hypothesized that it could trigger heart disease, a hypothesis, btw., that was not disproven, but simply kept quiet for the past 25+ years (Deeth. 1983)

• Little to no xanthine oxidase (=reductase) - While the idea that XOR (xanthine oxidoreductase), which is supposedly released during homogenization of bovine milk, could be a potential contributor to overall inflammation and cardiovascular disease has disappeared from the 'scientific radar' within the past couple of years (cf. Deeth. 1983; Berry. 2004) , it may still be of interest (and for certain populations such as people with increased gut permeability even of great importance) that camel milk apparently contains little to no xanthine oxidase - irrespective of whether you drink it raw, pasteurized or homogenized (Baghiani. 2003).
• Anticancer effects - Camels milk has been shown to trigger apoptosis (controlled cell death) in human breast cancer and liver cancer cells via epigenetic mechanisms (Korashi. Feb 2013; Korashi. May 2013).
• Antibacterial & antiviral effects -Camel milk prevents gram positive bacteria from growing and reduces the amounts and activity of gram-negative cultures (el Agamy. 1992). With the latter being among the primary drivers of lipopolysaccharide (LPS) and endotoxin induced inflammation (Ulevitch. 1999), camel milk could thus help to reduce local and systemic inflammation. Aside from its activity against rotavirus, the lactoferrin faction from camel milk appears to have protective effects against hepatitis C, as well (Redwan. 2007).
• Camel milk whole- & beta-caseins act as natural anti-oxidants and ACE-inhibitors - As Salami et al have shown the whole casein and beta-casein (β-CN) faction(s) of camel milk exert Angiotensin Converting Enzyme (ACE)-inhibitory (=blood pressure reducing) and antioxidant activity after they were hydrolyzed in the stomach (Salami. 2011). In a previous study, the same researchers had already determined that the whey fraction of camel milk exhibits significant anti-oxidant and antimicrobial activities, as well, and that those were up to 100% greater (depending on the essay and fraction the scientists used) than those of bovine whey protein (Salami. 2010).



Figure 1: A certain part of the population in Rajasthan (India) who consumes camel milk on a daily basis has been found to have a significantly reduced incidence of diabetes (not a single one!), impaired fasting glucose (-6%/-11%) and impaired glucose tolerance (-10%/-10%) than both non-camel milk drinking parts of the Raica community or other non-camel milk drinkers from the same region (based on Agrawal. 2007)

• Profound and long-lasting anti-diabetic effects - Camel milk has a long history of being used to tread type 1 diabetes in the Middle East (see figure 1; cf. Mohamad. 2009). Studies from animal models (dogs, Sbou. 2010) and humans (Agrawal. 2009; Mohamad. 2009) improved blood glucose, microalbumenia and secondary symptoms such as diabetic neuropathy. Probably also as a consequence of the small, but biologically active natural insulin content of camels milk (Malik .2013), the type 1 diabetics in a 2009 study by Agrawal could even reduce their insulin medication by 32% from 41µ/day to 28µ/day. In the 2-year follow up, the researchers report that "out of 12 subjects receiving camel milk, insulin requirement in 3 subjects reduced to zero" (Agrawal. 2011) - try that with metformin, let alone some of the other 'diabetes prolongation drugs'.
• Improved lipid metabolism - The 24 type one diabetics who consumed 500ml of plain camel milk per day for 6 months in the aforementioned 2009 study by Agrawal et al. for example exhibited -30% decreases in LDL and -66% decrease in triglycerides.
• Camel milk is an extraordinary good source of trace minerals - According to Al-Awidi et al. Camel milk contains 7-20x and 1-10x higher levels of manganese and iron than human milk, more zinc and comparable amounts of selenium, copper and other protein bound and thus highly bioavailable trace minerals (Al-Awadi. 2001).

And best of all, based on studies on people with cow's milk allergy, we know that the incidence of allergic reactions to camel milk is not only much lower, but also that 80% of cow's milk allergy sufferers can actually ingest camel milk without any unwanted side-effects (Cardoso. 2010; Ehlayel. 2011).

Figure 2: Even if you go solely by the amino acid composition (here expressed relative to the total amino acids), camel milk protein could be a valid replacement for bovine proteins (data based on Davis. 1994 & Beg. 1987)

This is also worth mentioning, because the host of great effects I listed above do - at least in parts - also occur with the unwarrantedly vilified bovine (=cow's) milk, which also contains ACE precursors (Saito. 2008), exert anti-cancer effects (Gill. 2000), and so much more (see "suggested readings" at the end of this article).

So, in the unfortunate case that you "ain't got no camel handy" at the moment and, due to "the current economy" (I hate when people say that) lack the $1300 to $1700 (Debacle. 2006) to buy your own, obviously not  pageant winning $16.5 million dirham camel, and tolerate bovine milk, just stick to the milk of the farmer you trust. After all, even if Camels were the better cows, you better have a gallon of cows milk in the fridge than a camel in the Arabian desert, right? Ah, wait that was a bird in the hand, right? ... ah, whatever ;-)

Suggested readings:

• Ask Dr. Andro: Are Colostrum and Milk Products in General Healthy Muscle Builders, a Waste of Money or Toxic Waste?
• Childhood Asthma: Children Born to Mothers Who Consume Semi-Skimmed Milk 8% More Likely, Kids of Whole Milk Drinking Mothers 15% Less Likely to Develop Asthma
• The Fat Truth Behind the Dairy Weight Loss Miracle: MUFA and PUFA Impair, Saturated Fat and Plenty of Micronutrients Drive Full-Fat Dairy-Powered Fat Loss.
• Higher Calcium Intake Greater Fatty Acid Oxidation!? True: Chronic & Acute Effect Size Comparable to Caffeine
• Read all about milk here at the SuppVersity

References:

1. Agrawal RP, Budania S, Sharma P, Gupta R, Kochar DK, Panwar RB, Sahani MS. Zero prevalence of diabetes in camel milk consuming Raica community of north-west Rajasthan, India. Diabetes Res Clin Pract. 2007 May;76(2):290-6.
2. Agrawal RP, Dogra R, Mohta N, Tiwari R, Singhal S, Sultania S. Beneficial effect of camel milk in diabetic nephropathy. Acta Biomed. 2009 Aug;80(2):131-4. 
3. Agrawal RP, Jain S, Shah S, Chopra A, Agarwal V. Effect of camel milk on glycemic control and insulin requirement in patients with type 1 diabetes: 2-years randomized controlled trial. Eur J Clin Nutr. 2011 Sep;65(9):1048-52. doi: 10.1038/ejcn.2011.98. Epub 2011 Jun 1.
4. Al-Awadi FM, Srikumar TS. Trace elements and their distribution in protein fractions of camel milk in comparison to other commonly consumed milks. J Dairy Res. 2001 Aug;68(3):463-9.
5. Baghiani A, Harrison R, Benboubetra M. Purification and partial characterisation of camel milk xanthine oxidoreductase. Arch Physiol Biochem. 2003 Dec;111(5):407-14.
6. Beg OU, von Bahr-Lindström H, Zaidi ZH, Jörnvall H. Characterization of a heterogeneous camel milk whey non-casein protein. FEBS Lett. 1987 Jun 1;216(2):270-4.
7. Berry CE, Hare JM. Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol. 2004 Mar 16;555(Pt 3):589-606.
8. Cardoso RR, Santos RM, Cardoso CR, Carvalho MO. Consumption of camel's milk by patients intolerant to lactose. A preliminary study. Rev Alerg Mex. 2010 Jan-Feb;57(1):26-32.
9. Davis TA, Nguyen HV, Garcia-Bravo R, Fiorotto ML, Jackson EM, Lewis DS, Lee DR, Reeds PJ. Amino acid composition of human milk is not unique. J Nutr. 1994 Jul;124(7):1126-32.
10. Deeth HC. Homogenized milk and atherosclerotic disease: a review. J Dairy Sci. 1983 Jul;66(7):1419-35.
11. Gill HS, Cross ML. Anticancer properties of bovine milk. Br J Nutr. 2000 Nov;84 Suppl 1:S161-6. Review.
12. Ehlayel MS, Hazeima KA, Al-Mesaifri F, Bener A. Camel milk: an alternative for cow's milk allergy in children. Allergy Asthma Proc. 2011 May-Jun;32(3):255-8.
13. el Agamy EI, Ruppanner R, Ismail A, Champagne CP, Assaf R. Antibacterial and antiviral activity of camel milk protective proteins. J Dairy Res. 1992 May;59(2):169-75. 
14. Gill HS, Cross ML. Anticancer properties of bovine milk. Br J Nutr. 2000 Nov;84 Suppl 1:S161-6. Review.
15. Korashy HM, El Gendy MA, Alhaider AA, El-Kadi AO. Camel milk modulates the expression of aryl hydrocarbon receptor-regulated genes, Cyp1a1, Nqo1, and Gsta1, in murine hepatoma Hepa 1c1c7 cells. J Biomed Biotechnol. 2013;2013:782642. Epub 2013 Feb 27.
16. Korashy HM, Maayah ZH, Abd-Allah AR, El-Kadi AO, Alhaider AA. Camel Milk Triggers Apoptotic Signaling Pathways in Human Hepatoma HepG2 and Breast Cancer MCF7 Cell Lines through Transcriptional Mechanism. J Biomed Biotechnol. 2013;2013:593195. Epub 2013 May 13.
17. Debacle J. Long or Short Capital. Camels, The Next Big Thing. August 1, 2006. < http://longorshortcapital.com/camels-the-next-big-thing.htm > received on July 13, 2013
18. Malik A, Al-Senaidy A, Skrzypczak-Jankun E, Jankun J. A study of the anti-diabetic agents of camel milk. Int J Mol Med. 2013 Sep;30(3):585-92.
19. Mohamad RH, Zekry ZK, Al-Mehdar HA, Salama O, El-Shaieb SE, El-Basmy AA, Al-said MG, Sharawy SM. Camel milk as an adjuvant therapy for the treatment of type 1 diabetes: verification of a traditional ethnomedical practice. J Med Food. 2009 Apr;12(2):461-5.
20. Salami M, Moosavi-Movahedi AA, Ehsani MR, Yousefi R, Haertlé T, Chobert JM, Razavi SH, Henrich R, Balalaie S, Ebadi SA, Pourtakdoost S, Niasari-Naslaji A. Improvement of the antimicrobial and antioxidant activities of camel and bovine whey proteins by limited proteolysis. J Agric Food Chem. 2010 Mar 24;58(6):3297-302.
21. Salami M, Moosavi-Movahedi AA, Moosavi-Movahedi F, Ehsani MR, Yousefi R, Farhadi M, Niasari-Naslaji A, Saboury AA, Chobert JM, Haertlé T. Biological activity of camel milk casein following enzymatic digestion. J Dairy Res. 2011 Nov;78(4):471-8.
22. Redwan el-RM, Tabll A. Camel lactoferrin markedly inhibits hepatitis C virus genotype 4 infection of human peripheral blood leukocytes. J Immunoassay Immunochem. 2007;28(3):267-77.
23. Saito T. Antihypertensive peptides derived from bovine casein and whey proteins. Adv Exp Med Biol. 2008;606:295-317. Review.
24. Sboui A, Khorchani T, Djegham M, Agrebi A, Elhatmi H, Belhadj O. Anti-diabetic effect of camel milk in alloxan-induced diabetic dogs: a dose-response experiment. J Anim Physiol Anim Nutr (Berl). 2010 Aug 1;94(4):540-6.
25. Ulevitch RJ, Tobias PS. Recognition of gram-negative bacteria and endotoxin by the innate immune system. Curr Opin Immunol. 1999 Feb;11(1):19-22.

Higher Calcium Intake Greater Fatty Acid Oxidation!? True: Chronic & Acute Effect Size Comparable to Caffeine

Image 1: When people hear they should increase their calcium intake, they either think of pills and tablets or milk and dairy in general. The fact that all greens, nuts and many seeds contain tons of calcium, as well, is commonly overlooked (for more high calcium foods see table 1, below).

"Increase your calcium intake, if you want to lose body fat!" I honestly don't even remember, when I've heard this statement for the first time, but it was way before I started questioning general recommendations on nutrition. Meanwhile, my blind faith in dietary recommendations and expert advice has faded, yet the general advice to "increase your calcium intake" is still so ubiquitous that searching for it on Google returns 373.000 results within 0.24 seconds, searching for the same token yet with "magnesium" instead of calcium does only yield 11,900 results and even "increase your omega-3 intake" will deliver only a meager 17,500 results (4.6% of the results for calcium). The publication of a very recent review by Gonzales, Rumbold and Stevenson in the "early view" section of Obesity Reviews was therefore a very welcome opportunity for me to take another look at the effects high(er) dietary / supplemental calcium intakes exert not just on weight loss, but also on postprandial and 24h fatty acid oxidation.

Will calcium make you lean or at least help you to stay lean?

Calcium intake has been associated with lower body mass index and adiposity (body fatness) for decades and supporting evidence from epidemiological studies is abundant (see references 1-15). If you take a look the highly opinionated paleosphere, the most recent consensus on calcium and the most prominent (I did not say best ;-) dietary calcium source, dairy, is however that dairy is the devil and calcium supplements are made of the devil's excrements... and in fact, at least the latter may be dead-on. After all, one of the purported mechanisms that could explain the associations of high(er) calcium intakes and low(er) body fat levels is directly related to excrements - the fat content of your excrements, to be precise, of which a handful of studies have shown that it is increased (see references 18-21) in response to calcium supplementation / increases in dietary calcium.

Figure 1: When added to a regular calorically reduced diet supplemental and even more dairy calcium ramp up its efficacy (data based on Zemel. 2004).

Sufficiently powered and well-conducted trials support the epidemiological data: As Trowman et al. pointed out in another systematic review of the literature (Trowman. 2006), most trials did not adequately make up for biases that may have been introduced by weak allocation methods and the only "adequately powered" study that was specifically designed to identify the effects of calcium supplementation on weight loss on an energy restricted (-500kcal) diet over a sufficiently long time period (24 weeks) by Zemel. et al. yielded a highly significant increases weight and fat loss for both supplemental and dairy calcium (see figure 1). An effect, of which the researchers state that it is most likely mediated by the inhibition of the 1,25-dihydoxyvitamin D increases with which our body reacts in response to low-calcium diets and thus stimulate adipocyte Ca2+ influx and, as a consequence, lipogenesis, while simulataneously suppressing lipolysis, and increasing lipid accumulation.

The subsequent decrease in fatty acid and thus energy absorption can yet not fully explain the observed weight loss effects. According to Christensen et al. the latter would amount to roughly 2g/day and thus no more than 0.7kg of body fat per year (Christensen. 2009)! The data of the study be Zemel et al. (see red box), on the other hand, shows an absolute increase in weight loss of 4.5kg within no more than 24 weeks, which highlights the importance of other mechanisms such as...

• the aforementioned (see red box) reduction in 1,25-dihydroxyvitamin D expression and its pro-adipogenic (=promoting fat storage) and anti-adipolytic (=inhibiting fat burn) effects, or
• lower parathyroid hormone (PTH) levels and subsequently increased insulin sensitivity and sympathetic nervous system activity, which will in turn increase dietary induced thermogensis and fatty oxidation rates, and lastly
• gastrointestinal effects of dietary calcium (and dairy) on the release of peptides and hormones in the GI tract

all of which interact to increase energy expenditure, decrease the fat balance, increase energy loss (increased mitochondrial uncoupling; e.g. Shi. 2001) and reduce food intake, with the net effect of decreases in body weight and body fat levels.

Figure 2: Effects of chronic (top) and acute (bottom) high calcium intake on fat oxidation, as well as weighed averages (lower right);  Ca²⁺, calcium; DA, dairy (based on Gonzales. 2013)

The data from the initially mentioned meta-review by Gonzales et al. in figure 2 confirms the significance of these effects. Irrespective of the scenario, i.e. weight loss vs. weight maintenance, calcium sufficient vs. calcium deficient baseline diet and acute vs. chronic, an increase in dietary calcium from supplements or food sources lead to statistical significant increases in fatty acid oxidation, of which the researchers state that they are of "comparable magnitude with that seen with caffeine supplementation" (Gonzales. 2013).

Two reasons why you should prefer dietary (dairy) calcium: Efficacy and safety

Despite the fact that the difference is not statistically significant, the data Gonzales et al. collected and my own cursory review of pertinent studies, both suggest that contrary to the effects on fatty acid oxidation, which are, as Gonazeles et al. point out apparently slightly more pronounced in response to supplemental calcium (could simply be an effect of insufficient adherence in the dietary calcium groups; popping a pill is easier and above all  more convenient than eating 2-3x servings of dairy), dietary calcium sources elicit greater weight- and fat-loss effects than supplements. It stands to reason that part of this may be explained by confounding factors such as

Table 1: High calcium foods with a calcium to phosphorus ratio of 1:0.14 (Turnip) to 1:0.7 (Celery); data adapted from parrottalk.com; eating those foods will also shift your often too low calcium to phosphorus ratio in the "right" direction

• the satiety effect - someone who has already eaten a cup of calcium-rich broccoli (1 cup: 178mg Ca) and a yogurt (6oz = 170mg: 350mg) will be less likely to have another 300g of pasta (100g, cooked: 1mg)
• the nutrient matrix effect - especially dairy, but also other calcium rich foods, contain other nutrients which exert anti-obesity effects, think of the bioactive peptides in milk (1 cup: 300mg Ca), for example, or Chinese cabbage (1 cup: 400mg Ca; cf. "Lose Weight, Improve Your Blood Lipids, Reduce Estrogen, Protect Yourself Against Chromosomal Damage and Defeat Prostate Cancer With Cabbage.")

If you add to that the already inconclusive evidence that high(er) calcium intake precipitates heart disease (e.g. deBoer. 2008) refer exclusively to supplemental calcium (and most data is from postmenopausal women on synthetic hormone therapy), I suggest you head right over to one of the nutrition analyzers to see if you get at ~900mg-1,300mg of calcium in your diet. What your calcium to phosphor ratio looks like (should be 1:1) and whether another cup of spinach and a glass of milk once in a while could not maybe help you to shed some additional pounds of body fat.

Update: I forgot to mention a previous article of mine on potential toxicity issues with many commercially available calcium supplements which could be a hitherto overlooked confounding factor in the etiology of heart disease - see "Alarmingly High Levels of Lead in Calcium Supplements: Pb Content per Serving Up to 18x Over 'Acceptable Levels'"

References: 

1. Beydoun MA, Gary TL, Caballero BH, Lawrence RS, Cheskin LJ, Wang Y. Ethnic differences in dairy and related nutrient consumption among US adults and their association with obesity, central obesity, and the metabolic syndrome. Am J Clin Nutr 2008; 87: 1914–1925.
2. Boon N, Koppes LL, Saris WH, Van Mechelen W. The relation between calcium intake and body composition in a Dutch population: the Amsterdam Growth and Health Longitudinal Study. Am J Epidemiol 2005; 162: 27–32.
3. Buchowski MS, Semenya J, Johnson AO. Dietary calcium intake in lactose maldigesting intolerant and tolerant African-American women. J Am Coll Nutr 2002; 21: 47–54.
4. Eilat-Adar S, Xu J, Loria C et al. Dietary calcium is associated with body mass index and body fat in American Indians. J Nutr 2007; 137: 1955–1960.
5. Heaney RP, Davies KM, Barger-Lux MJ. Calcium and weight: clinical studies. J Am Coll Nutr 2002; 21: 152S–155S.
6. Heaney RP. Normalizing calcium intake: projected population effects for body weight. J Nutr 2003; 133: 268S–270S.
7. Jacqmain M, Doucet E, Despres JP, Bouchard C, Tremblay A. Calcium intake, body composition, and lipoprotein-lipid concentrations in adults. Am J Clin Nutr 2003; 77: 1448–1452.
8. Loos RJ, Rankinen T, Leon AS et al. Calcium intake is associated with adiposity in Black and White men and White women of the HERITAGE Family Study. J Nutr 2004; 134: 1772–1778.
9. Lovejoy JC, Champagne CM, Smith SR, de Jonge L, Xie H. Ethnic differences in dietary intakes, physical activity, and energy expenditure in middle-aged, premenopausal women: the Healthy Transitions Study. Am J Clin Nutr 2001; 74: 90–95.
10. McCarron DA, Morris CD, Henry HJ, Stanton JL. Blood pressure and nutrient intake in the United States. Science 1984; 224: 1392–1398.
11. Melanson EL, Sharp TA, Schneider J, Donahoo WT, Grunwald GK, Hill JO. Relation between calcium intake and fat oxidation in adult humans. Int J Obes Relat Metab Disord 2003; 27: 196–203.
12. Mirmiran P, Esmaillzadeh A, Azizi F. Dairy consumption and body mass index: an inverse relationship. Int J Obes (Lond). 2005; 29: 115–121.
13. Tidwell DK, Valliant MW. Higher amounts of body fat are associated with inadequate intakes of calcium and vitamin D in African American women. Nutr Res 2011; 31: 527–536.
14. Zemel MB, Shi H, Greer B, Dirienzo D, Zemel PC. Regulation of adiposity by dietary calcium. FASEB J 2000; 14: 1132–1138.
15. Zemel MB. Calcium and dairy modulation of obesity risk. Obes Res 2005; 13: 192–193.
16. Trowman R, Dumville JC, Hahn S, Torgerson DJ. A systematic review of the effects of calcium supplementation on body weight. Br J Nutr 2006; 95: 1033–1038.
17. Zemel MB, Thompson W, Milstead A, Morris K, Campbell P. Calcium and dairy acceleration of weight and fat loss during energy restriction in obese adults. Obes Res. 2004 Apr;12(4):582-90.
18. Boon N, Hul GBJ, Stegen JHCH et al. An intervention study of the effects of calcium intake on faecal fat excretion, energy metabolism and adipose tissue mRNA expression of lipid-metabolism related proteins. Int J Obes 2007; 31: 1704–1712. 
19. Buchowski MS, Aslam M, Dossett C, Dorminy C, Acra S. Effect of dairy and nondairy calcium on fecal fat excretion in lactose digester and maldigester obese adults. Int J Obes 2010; 34: 127–135. 
20. Jacobsen R, Lorenzen JK, Toubro S, Krog-Mikkelsen I, Astrup A. Effect of short-term high dietary calcium intake on 24-h energy expenditure, fat oxidation, and fecal fat excretion. Int J Obes 2005; 29: 292–301. 
21. Heaney RP, Recker RR. Estimation of true calcium absorption. Ann Intern Med 1985; 103: 516–521. 
22. Christensen R, Lorenzen JK, Svith CR et al. Effect of calcium from dairy and dietary supplements on faecal fat excretion: a meta-analysis of randomized controlled trials. Obes Rev 2009; 10: 475–486. 
23. Gonzalez JT, Rumbold PL, Stevenson EJ. Effect of calcium intake on fat oxidation in adults: a meta-analysis of randomized, controlled trials. Obes Rev. 2013 Jun 19.
24. De Boer IH, Tinker LF, Connelly S, Curb JD, Howard BV, Kestenbaum B, Larson JC, Manson JE, Margolis KL, Siscovick DS, Weiss NS; Women's Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of incident diabetes in the Women's Health Initiative. Diabetes Care. 2008 Apr;31(4):701-7.
25. Shi H, Dirienzo D, Zemel MB. Effects of dietary calcium on adipocyte lipid metabolism and body weight regulation in energy-restricted aP2-agouti transgenic mice. FASEB J. 2001 Feb;15(2):291-3.

Childhood Asthma: Children Born to Mothers Who Consume Semi-Skimmed Milk 8% More Likely, Kids of Whole Milk Drinking Mothers 15% Less Likely to Develop Asthma

Image 1: Better make sure your "mother's milk" (the milk you drink while you or your significant other are pregnant) is full fat!

I don't know if you have listened to my "brother" Carl Lanore's Super Human Radio interview with Boyd Eaton, yesterday, but if you did, you will probably remember that the two also broached the issue of dairy consumption on a paleo diet. And while many of you may have been surprised to hear that Eaton does consume milk products on a regular basis, it is probably even more intriguing that the show came full-circle only a couple of minutes later, when Carl who had just addressed the issue of iron-overload and how that relates to the relative abundance of meat in an ancestral diet, read my facebook message about the beneficial effects of milk proteins, Zunquin et al. observed in a 2006 trial rodent trial intended to simulate the potential side effects of high dose iron supplementation to replete iron stores in iron-depleted athletes (Zunquin. 2006).

Milk allergy or allergy due to the lack of full-fat milk - is that the question?

Yet while the Zunquin study is by no means the only scientific evidence that nature's original meal replacement, irrespective of whether or not it may be "intended for human consumption" can exert potent health effects (cf. Barfray. 2003), the pros and cons of a high(er) intake of dairy is still a matter of constant debate. Other than within the paleosphere, the public and scientific debate does yet usually revolve around the notion of low- vs. high fat dairy, with the common recommendation to "choose low fat dairy in order to avoid the unhealthy saturated fats that come with the full-fat variety".

Figure 1: Associations between mothers' consumption of milk and dairy during pregnancy and incidence of early childhood asthma (18 months) in children from the Danish national Birth Cohort; data expressed as differences to no-consumption (data based on Masolva. 2013)

Aside from the downside of non-existent yet potentially healthy levels of certain fatty acids, such as conjugated linolic acid (yeah, the one that can kill empty fat cells, cf. "Nasty Insights into the Yo-Yo-Effect: Lower Body Fat Sticks and From Fit2Fat There's no Easy Way Back!"), the reduced absorption and presence of fat-soluble nutrients and the necessity to add sugar or artificial flavors, as well as chemicals to modify the taste and mouth-feel of those watery low-fat dairy products, a recent study from Department of Nutrition at the Harvard School of Public Health in Boston does now provide compelling evidence that either one or all of the former aspects, or a hitherto not elucidated difference between skim and full-fat dairy products increases children who are born to mothers who consume >5 portions of semi-skimmed milk per week during their pregnancy have an 8% increased risk of developing childhood asthma and a 40% increase in risk of developing allergic rhinitis later in life (Maslova. 2013).

Table 1: If you are interested in other sources of CLA (and omega-3), in general, and the difference between grass- and grainfed beef, in particular, check out this table from a Daley et al. (Daily. 2013)

What's even more intriguing, though, is that the consumption of equal amounts of full fat milk was associated with a statistically significant 25%(!) reduction in asthma-risk (and recurrent wheeze symptoms) in the ~60,000 children / mother pairs from the dataset of the Danish National Birth Cohort the US scientists analyzed. Similarly, there was a

"dose–response was present for semiskimmed milk intake, while any intake of full-fat yoghurt appeared to be protective of child asthma" (Maslova. 2013)

that did, just as the aforementioned results, remain significant, even when the data was adjusted for the intake of other allegedly beneficial foods (fruit and vegetables) and nutrients (vitamin E, vitamin D, Se, Zn from diet and supplements).

So are those the CLAs and other ruminant trans-fats?

While Malsova et al. fail to give a clearcut answer on what the underlying reasons for these observations are, their detailed analysis of the data does yield some evidence that CLAs and other ruminant trans-fatty acids cannot explain the differences, as they showed similar correlations with both full-fat and semi-skimmed milk intake and were "not associated with either the early or later childhood outcomes" (Maslova. 2013).

Image 2: Not, not all full-fat milk drinkers worked on a farm ;-)

An analysis of other potentially confounding lifestyle factors yielded similarly inconclusive results so that this leaves us without a causal explanation for either the protective effect of whole milk and full-fat yogurt intake on early childhood asthma or the increased risk to develop wheeze at 18 months in children born to high consumers of semi-skimmed milk. In the absence of any information of what happened in the course of the following 7-years it appears futile come up with any hypothesis that would explain the direct associations of maternal low-fat yoghurt consumption with child asthma and allergic rhinitis and the "suggestive" relationship of the latter with total milk intake, anyways. And as the scientists say:

The diversity and complexity of our results make it difficult to interpret and propose a single agent mechanism, yet the consistent associations with low-fat yoghurt for later childhood outcomes suggest that compounds specific to this food, such as artificial sweeteners, may play a role.

Interestingly, they specifically refer to the use of aspartame as the "primary" artificial sweetener in the Danish food supply since the 1980s, but cite a - at least in my humble opinion - highly biased source (Gideon. 2010) on that issue without even providing a single scientific study that would implicate aspartame as a factor involved in the etiology of asthma (+my brief research shows, there is none).

Image 3: Too much statistical shenanigan involved in the ER data for my liking.

A note on additional data evaluated in the study: The scientists make use of the actual hospital admissions due to asthmatic reactions as another source for their study data. Unfortunately, those only contribute to the already confusing results, because they suggest that despite the fact that the incidence of early childhood asthma is lower (other data), the chance to end up in hospital, as assessed by data from the Danish National Patient Registry appears to be higher in children born to mothers with a high full fat milk intake (+30%), and minimally reduced for children whose mothers consumed the same amount of skimmed dairy - it is however questionable how reliable this 3rd hand data which had to be linked back to the central person registry first and ran through multiple processing steps actually is (same for data from the Register of Medicinal Product Statistics).

As far as the underlying mechanisms are concerned this leaves us with but one relatively certain conclusion: The scientists' initial hypothesis that ruminant trans-fatty acids could play a causal role in the development of allergic disease development cannot be upheld in view of the inverse associations Maslova et al. found between the CLA content and the risk to develop asthma and/or allergic rhinitis across products with different fat content.

Suggested reading:

• Ask Dr. Andro: Are Colostrum and Milk Products in General Healthy Muscle Builders, a Waste of Money or Toxic Waste? 
• Whey and Casein Work Hand in Hand for Protein Anabolism, but Scientists Overlook Fat, When They Reassemble Milk  
• Coke vs. Diet Coke vs. Milk - The "Unhealthy Beverage Shoot-Out": Milk Reduces, Coke Increases Visceral Fat. Dreaded Diet Coke on Par With Plain Water  
• The Fat Truth Behind the Dairy Weight Loss Miracle: MUFA and PUFA Impair, Saturated Fat and Plenty of Micronutrients Drive Full-Fat Dairy-Powered Fat Loss. 
• Want B12, But Hate Meat? Drink Milk! SNAC-Fortified Cyanocobalamin 136% More Bioavailable Than Standard B12 - Still Less Effective Than B12 From Cow's Milk

References:

1. Bartfay WJ, Davis MT, Medves JM, Lugowski S. Milk whey protein decreases oxygen free radical production in a murine model of chronic iron-overload cardiomyopathy. Can J Cardiol. 2003 Sep;19(10):1163-8. 
2. Daley CA, Abbott A, Doyle PS, Nader GA, Larson S. A review of fatty acid profiles and antioxidant content in grass-fed and grain-fed beef. Nutr J. 2010 Mar 10;9:10.
3. Gideon B (2010) Aspartam: Nu også i ikke ‘Light’ produkter. < http://infowars.dk/content/aspartam-nu-ogs%C3% A5-i-ikke-light-produkter > last accessed on July 10, 2013
4. Maslova E, Halldorsson TI, Strøm M, Olsen SF. Low-fat yoghurt intake in pregnancy associated with increased child asthma and allergic rhinitis risk: a prospective cohort study. Journal of Nutritional Science (2013), vol. 1, e5.
5. Zunquin G, Rouleau V, Bouhallab S, Bureau F, Theunynck D, Rousselot P, Arhan P, Bougle D. Iron and exercise induced alterations in antioxidant status. Protection by dietary milk proteins. Free Radic Res. 2006 May;40(5):535-42.

Fiber Up Your Foods, Omega-3 Preload For Female Fat Loss, 50+ Ways to Treat Constipation, Serotonergic Peptides in Milk, Weight Cycling & Reduced Metabolic Rates, Exercise & 102% Weight Loss From Fat - Plus: More Short News

Inulin enriched foods are good for your gut, your waistline and your pancreas (anti-diabesity effect) and what's more inulin is also on the list of anti-constipation agents,

100g that's this week's SuppVersity figure of the week and that despite the fact that it is the amount of fat you are going to gain within one year when your metabolic rate is 100kcal below where it should be (Piaggi. 2013)... Where it should be? Yeah, ok I know that's idiotic, but if you read today's news-item about the down-regulation of the metabolic rate due to YoYo-dieting the picture that emerges is that of yet another vicious cycle that leads directly into a weight spiral that knows but one direction: upwards!

Another one of today's news-items does however hint at a solution: Just lose 102% fat! What? I see I got you interested. So what are you waiting for? Lot's of good stuff today. So much in fact that let's spend no time and get right to the news-business ;-)

"Fiber up" you foods with prebiotics (inulin in particular)

Pretty obvious that these Spanish Christmas confections take a toll on your HbA1c ;-)

(Capriles. 2013; Garcia-Garcia. 2013) -- You've read about the benefits of "feeding the good guys" a couple of days ago. Now, aside from being a substrate for the purportedly beneficial gut bacteria fiber also changes the feel, taste and most importantly digestive properties of foods. A couple of recently published studies confirm that this can have pretty profound and in most cases highly desirable consequences.

Garcia-Garcia, for example, added some inulin (5%) to Turon, a traditional Spanish sweet treat that's made of toasted almonds, honey and sugar and fed 30g of the Christmas nougat-type confection to 32 healthy, normal-weight volunteers.

While the subjects in the "regular" Turon group had a slight but significant increase in HbA1c (long-term measure of blood glucose management) the blood glucose management of the 17 subjects in the active group did not budge. And while most subjects (64%, specifically those who conumed Turon as a Christmas snack on a regular basis) preferred the "classic" variety, at least 24% did actually like the inulin Turon better (Garcia-Garcia. 2013)

Gluten will interact with PPARs & gut bacteria and can thus precipitate insulin resistance (read more).

In a similar study, scientists were able to show that the addition of prebiotic inulin-type fructans to gluten-free bread (4 g of fructans per 50 g bread serving size) did

"[...] provide structure and gas retention during baking, thus improving GFB quality by yielding better specific volume, softer crumb, improved crust and crumb browning with enhanced sensory acceptance" (Capriles. 2013)

 and decreased the glycemic index and glycemic load of the gluten-free bread by 34% (from 71 to 48) and 33% (from 12 to 8), respectively.

Omega-3 loading improves weight loss in obese women

(Munro. 2013) -- According to a recently published study, a 4-week preload with 6 × 1 g capsules per day LC ω-3PUFA (fish oil) each comprising 70 mg EPA and 270 mg DHA, increased the amount of weight the female (and only the female!) participants of a very low calorie weight loss intervention lost in the subsequent 8-weeks.

Despite being statistically significant, the 1.4% increase in bod weight loss is yet not so pronounced that anyone whose been dieint with LC-PUFA preload in the past should now be fretting about having missed out on this great chance of getting ripped. If you are a man, the protocol would have been useless, anyways.

Constipated? Review offers three types of "solutions" - in some cases a literal sense

(Gelinas. 2013) -- If you are one out of five, chances are you belong to the 20% of the world's population who suffer from constipation on a regular base. If that's the case, you may want to consider one of the following "treatment" strategies, Pierre Galinas mentions in his latest review of the literature:

• 

  Table 1: Relative laxative potential of 50 food ingredients for the prevention of constipation

  Bulking agents  - They soften the stool by binding water; examples are psyllium seed husk, wheat bran, methylcellulose, calcium polycarbophil; are considered "mild" and are not habit forming, but may cause abdominal pain and bloating because of gas formation
• Osmotic agents - They also soften the stool but ba a dfferent mechanism than the bulk fiber, they create an osmotic gradient, which will distend the intestines and stimulates a contractile response; examples are lactulose, sorbitol, mannitol, polyethylene glycol (PEG), magnesium hydroxide (milk of magnesia), sodium phosphate; side effects are gas, and the offensive taste (of some)
• Softeners and lubricants  - They  lubricate (oil) and soften (detergent) the stool; examples are sodium docusate and various mineral oils; pretty milk
• Stimulants - Just like the stims in a fat burner get you going, these get your colon going; examples are epson salts (magnesium sulphate heptahydrate), bisacodyl, sodium picosulphate, sodium sulphate, magnesium oxide, phenolphthalein; they taste offensive, but don't produce gas
• Herbal teas - Provide water and can increase bowel frequency; examples are anthracenes derivatives (senna; aloe; cascara, Frangula bark); unfortunately they taste offensive and work almost immediately; moreover tolerance builds up pretty fast

As you can see there are different ways to get going with the bulk agent aka an increase in fiber intake being the only healthy long-term solution.

Even unhappy cows produce "Happy Milk"

"Mutant Milk" is homogenized milk a potential threat to your health (learn more)?

(Nongonierma. 2013) -- Three days ago a paper by Alice Nongonierma and her colleagues was published ahead of print on the website of the Journal of Food & Function. In the said paper, the researchers describe an experiment, in the course of which they were able to proof that hydrolyzed milk proteins contain a peptides that "behave as serotonin 2C (5-HT2c) receptor agonists" (Nongenierma. 2013). According to the scientists, the bioactive peptides have a relatively low molecular mass (< 1 kDa) and are hydrophobic in nature. With the 5-HT2c receptor being more than just a pharmacological target for the treatment of depression and anxiety, but also a trigger of neurogenesis (growth of new neurons) in the hippocampus (Millan. 2005), this certainly is good news for all the milk junkies out there - or could the serotonine-like effects make you fat?

Magic anti-diabetic mushrooms

(Su. 2013) -- Not what you are thinking now, folks! That's Traditional Chinese Medicine. After all, mushrooms such as Coriolus versicolor and Grifola frondosa have been used in TCM for centuries now. As a recent study by Scientsts from Kang Jien BioTech confirms rightly, so. Extracts from both mushroom had potent inhibitory effects on the carbohydrate digesting enzymes α-amylase and α-glucosidase. With Coriolus being a better inhibitor of the former and Grifola a more potent inhibitor of the latter enzymes.

How this relates to glucose control? Easy: If you don't disentangle the complex carbs your body cannot access their sugar content and if you do it only very slowly even "high" GI starches suddenly turn into low GI foods.

Weight cycling does not forestall future weight loss, but it makes it harder

Geoffrey Cannon's "Dieting Makes You Fat" was first published in 1983 but is that true? Does dieting always make you fatter and would it be better so simply surrender   (learn more)?

(Bosy-Westphal. 2013) -- While the ups and downs in body weight so many dieters are experiencing on a regular basis do not, as it was long suspected, ruin your body composition. A paper that has been published roughly a week ago in the International Journal of Obesitysuggests that another often touted downside, namely the long-term creeping down-regulation of the basal energy expenditure is unfortunately very real.

According to the analysis of the researchers from the Christian-Albrecht University in Kiel, Germany, the 27 "weight regainers" (after ~30% of loss) showed a reduced REE adjusted for changes in organ and tissue masses after weight loss that was not present in the 20 previously weight stable, yet likewise overweight / obese subjects in the control group of the researchers' 13-week dietary intervention study.

It is however not sure, whether this actually is a result of previous weight cycling or vice versa; meaning that the people with the ups and downs in body weight are the ones whose metabolism shuts down the easiest. The study at hand was obviously not able to exclude this possibility.

More than 100% weight loss from fat? How is that supposed to work?

(Hall. 2013) -- Actually this study was published late in the year 2013, that it still made it to On Short Notice has two reasons. Reason #1 is that it was an Epub way ahead of print. Reason #2 is that the figures the author reports appear to be pretty nonsensical. I mean how on earth can the projection K.. Hall from the National Institute of Health in Bethesda made based on data from the Biggest Loser camp yield a net weight loss of 24kg of which more than 100% (102% to be precise) came from the exuberant body fat stores of the (>70kg for the average participant) of the "big losers"?

For the researchers who worked with the Biggest Losers the highly successful TV show was a fluke. Having a TV station pay for their "research" certainly is something extraordinary and against and the study at hand is only the latest publication based on data from the Biggest Loser camp (read up on a previous news item)

The answer is actually pretty straight forward and underlines the efficacy of exercise as a weight loss tool that won't leave you skinny fat, but lean and more muscular. After all, the initially counter-intuitive +2% extra came from the increase in lean mass the Big Losers experienced despite being on a 1,300kcal-1,600kcal diet and working out at a "vigorous intensity" for 3.1h and 1.1h per day in phase 1 and phase 2 of the boot-camp intervention (the simulation of a diet only intervention yielded a slightly larger total weight loss yet with only 65% of the weight coming from the fat stores).

The one thing I am a bit skeptical about is whether Hall's prediction that the weight loss will be sustainable with no more than 20min/day of, once again, "vigorous" exercise per day. I mean that probably would be true in the sheltered environment of the weight loss camp. In a real life scenario, on the other hand, the super size menus, family pizzas and cosy TV couches are probably too much of a temptation for the many of the Big Losers.

---

Wine was yesterday! Chocolate liqueur is the future of healthy alcohol consumption (learn more)

That's all for today, at least as far as On Short Notice is concerned. By now the majority of you should yet be aware that there's always more... correct, the Facebook News - not sure if you notices, but you can actually see the latest items in the side-bar of the SuppVersity. To make sure you don't miss any of them it would yet be wise to simply "like" the SuppVersity on Facebook and/or register as a follower to my Twitter Account. It's hard-wired to the Facebook page, so if you are into tweeting.. maybe you prefer being notified this way.

Whatever your social media service provide of choice may be, I am pretty sure that you don't want to miss news such as the one on the total phenols, flavonoids, flavan-3-ols and proanthocyanidins of chocolate liqueur and how this may make it a better choice for your daily dose of "healthy" alcohol than wine ;-)

References:

• Carpiles VD, Aréas JADG. Effects of prebiotic inulin-type fructans on structure, quality, sensory acceptance and glycemic response of gluten-free breads. Food & Function. 03 Oct 2013 [Epub] 
• Garcia-Garcia E., Narbona E, Carbonell-Barrachina AA, Sanchez-Soriano J, Roche E. The effect of consumption of inulin-enriched Turrón upon blood serum lipids over a 5-week period. International Journal of Food Science & Technology. 2013; 48(2):405–411.
• Gelinas P. Preventing constipation: a review of the laxative potential of food ingredients. International Journal of Food Science & Technology. 2013; 48(3):445–467. 
• Hall KD. Diet versus exercise in "The Biggest Loser" weight loss competition. Obesity (Silver Spring). 2013 Oct 3. doi: 10.1002/oby.20065. [Epub ahead of print]
• Lai MN, Ng LT. Inhibitory effects of medicinal mushrooms on α-amylase and α-glucosidase – enzymes related to hyperglycemia. Food & Function. 2013 [Epub ahead of print].
  
• Millan MJ. Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie. 2005 Sep-Oct;60(5):441-60.
• Munro IA, Garg ML. Prior supplementation with long chain omega-3 polyunsaturated fatty acids promotes weight loss in obese adults: a double-blinded randomised controlled trial. Food & Function. February 2013 [Epub ahead of print].
• Nongonierma A,  Schellekens H, Dinan T,  Cryan JF, Fitzgerald D. Milk protein hydrolysates activate 5-HT2c serotonin receptors: influence of the starting substrate and isolation of bioactive fractions. Food & Function. 2013 [Epub ahead of print]
• Piaggi P, Thearle MS, Bogardus C, Krakoff J. Lower Energy Expenditure Predicts Long-Term Increases in Weight and Fat Mass. JCEM. 2013; jc.2013-3529;