"Milk Kills," Study Says and Everyone is Afraid. Is This More Than Fearmongering Bullsh*t? Methodological Issues & Conflicting Evidence Would Suggest the Answer is "No!"

After reading this article you won't have to be afraid of milk any longer.

The editor of the British Medical Journal (BMJ) will be rubbing his / her hands. The paper by Karl Michaëlsson et al. (2014) that was published earlier this week, made it to the mainstream news in the US and Europe and did - at least at first sight - reflect well on his or her magazine. "The British Medical Journal saves you from intoxicating yourself with milk!" - That's great, right?

Well, in today's SuppVersity article, I am going to take a closer look at how "great" it actually is that studies like this hit the mainstream media, while less exciting, because beneficial studies on milk are not being mentioned at all ... unless, of course, it's the morally superior and allegedly healthier soy milk we are talking about *sarcastic laughter*

You can learn more about dairy at the SuppVersity

Dairy Has Branched-Chain Fatty Acids!

Is There Sth. Like a Dairy Weight Loss Miracle?

There is Good A2 and Bad A1 Dairy, True or False?

Lactulose For Your Gut & Overall Health

Is There a "Fat Advantage" for Dairy Lovers

Dairy, Diabetes, Estrogen, IGF-1, Cancer & More

Before we get to a detailed analysis of the analysis, let's briefly remind ourselves of the type of data we are dealing with. Data from the Swedish Mammography Cohort (all female subjects) and Cohort of Swedish Men (all male subjects) that was complemented by data from food questionnaire that were send out back in the late nineteen eighties (women) and -nineties (men) along with the invitation to participate in the respective cohort studies.

Figure 1: Flow chart of the study sample (Michaëlsson. 2014).

As you can see in Figure 1 we are dealing with a hell lot of data. Data of which we still should not forget that it is based on data of which Thompson, et al. were able to show that it has an accuracy of 45-52%, specifically for dairy products (Thompson. 2002).

Now, in the study by Thompson the subjects were asked about what they ate in the last 30 days. The data in the study at hand, however, is based on what subjects said about how often they drank milk in the past 365 days! A fact that is not likely to make the data any more accurate.

Furthermore, I assume that all of you will have heard of people who change their dietary habits over time, right? Well, for Michaëlsson et al. this is obviously news. Otherwise they would not have relied exclusively data that was gathered, when the subjects were enlisted for the cohort study in the late 1980s / 1990s, when they were trying to identify the reason that 15,541 of the men and women died over the course of the 10-20 year follow-up.
Speaking of 20 years. That's the time that passed between being enlisted and speculating about their daily food intake when the 90 303 women aged 39-74 were enlisted in the Swedish Mammography Cohort and the 31st of December 2010, which was used as an end point for the analysis.

Figure 2: Mortality raters (raw data) according to milk intake in glasses / grams (Michaëlsson. 2014).

Malicious gossip would now probably have it that the additional 10 year gap, i.e. 10 more years to start eating completely differently, alone, could explain why we see a significant negative effect of drinking milk in the female, but not the male participants, for whom the interlude between the food frequency questionnaire and the end point of the study was ~50% smaller.

Figure 3: Adjusted predictions of urine 8-iso-PGF2α, a marker of oxidative stress, in 892 women (based on cross sectional data, mean age 70 years) and 700 men (Michaëlsson. 2014).

A similar criticism can be brought forward with respect to the allegedly "objective" measurements of 8-iso-PGF2α, a marker of oxidative stress, that was assessed in only 892 women (based on cross sectional data, mean age 70 years) and only 700 men, i.e. 1.4% of the female and 1.5% of the male participants, where the "trend" towards increased inflammation reached - once gain! - significance only in the female study participants (see Figure 3).

Homogenization may in fact be a problem. You find that's bogus? There is evidence that suggests that homogenization, not pasteurization is a serious problem | more.

What do commenters say? If you take a closer look at the hitherto published comments (retrieved on October 31, 2015) on the BMJ website, you will find commenters mentioning (1) the obvious association between having too little calcium <> fractures and the desire to increase ones calcium intake by drinking more milk (Kerr, J. Prof. of Epidemiology in Columbia), (2) the absence (or as Rom R. Hill from the Newcastle University says "significant omission") of a clear distinction between raw and pasteurized milk and low fat and full fat milk that makes the study, in Kerr's eyes, more or less meaningless, (3) last but not least, an unknown commenter mentions the issue of hormone, antibiotics and analgesic abuse in modern milk production and highlights that somatotropin (rBST) was still allowed in the EU, when the data from the study was collected. In view of the fact that rBST can affect hormonal and metabolic growth factors including human serum insulin-like growth factors (IGF), this could be another reason specifically for an increase in cancer related mortality (Allen. 2002; WHO. 2006).

Learn more about dairy from Liz in a previous SuppVersity article, i.e. "Dairy - The Good, Bad or Ugly?"

Moreover, the hazard ratios you read of in the news may have been adjusted, but the question remains, whether the adjustment could correctly make up for the fact that men and/or women who consumed more milk, ...

1. consumed significantly more energy on a daily basis (39% more in women, 24% more in men),
2. consumed significantly more saturated (36% more in women) and total fat, and
3. were significantly less likely to use bone building calcium supplements (15 % less in women).

Of these three factors (1) + (2) could explain the increased mortality and cancer risk in women and (3) could explain why women, but not men have a higher risk of hip, but not general bone fracture (hypothetically!).

My recommendation: Don't overrate the results of the study at hand. It has truckloads of methodological shortcomings, a tinge of the hysterical attention grabbing sensationalism and, most importantly, it stand in stark contrast to previous results which indicate that...

Figure 4: If you look at all the evidence, you will see that milk is more likely to protect than to kill you (Elwood. 2008; Bonthuis. 2010; Goldbohm. 2011)

• a high intake of milk is associated with a 16% reduced risk of cardiovascular disease and an 8% reduced risk of diabetes, two of the most important health issues that will have you pass away years, if not decades before your time (Elwood. 2008 | meta-analysis of 15 pertinent studies),
• Australians with a high fat milk intake of of 339g/day or more have a 69% reduced risk of dying from cardiovascular disease than their peers (Bonthuis. 2010),
• Dutch full-fat dairy connoisseurs have a 1% reduced all-cause mortality risk for each 10g of full fat dairy consumption per day (Goldbohm. 2011).

And in spite of the fact that several other studies find no beneficial effects of milk consumption of CVD or all-cause mortality (e.g. non-significant -23% in partly adjusted model in the Whitehall II study), it appears very unlikely that "milk kills". That this statement makes appalling headlines and will get a lot of clicks on the Internet, on the other hand, stands out of question | Read the whole paper for free @ the BMJ Website make up your mind and tell me on Facebook what you think.

References:

• Allen, Naomi E., et al. "The associations of diet with serum insulin-like growth factor I and its main binding proteins in 292 women meat-eaters, vegetarians, and vegans." Cancer Epidemiology Biomarkers & Prevention 11.11 (2002): 1441-1448.
• Bonthuis, M., et al. "Dairy consumption and patterns of mortality of Australian adults." European journal of clinical nutrition 64.6 (2010): 569-577.
• Elwood, Peter C., et al. "The survival advantage of milk and dairy consumption: an overview of evidence from cohort studies of vascular diseases, diabetes and cancer." Journal of the American College of Nutrition 27.6 (2008): 723S-734S.
• Goldbohm, R. Alexandra, et al. "Dairy consumption and 10-y total and cardiovascular mortality: a prospective cohort study in the Netherlands." The American journal of clinical nutrition (2011): ajcn-000430.
• Michaëlsson, Karl, et al. "Milk intake and risk of mortality and fractures in women and men: cohort studies." BMJ 349 (2014): g6015.
• Thompson, Frances E., et al. "Cognitive research enhances accuracy of food frequency questionnaire reports: results of an experimental validation study." Journal of the American Dietetic Association 102.2 (2002): 212-225.
• WHO Expert Committee on Food Additives. "Toxicological evaluation of certain veterinary drug residues in food/prepared by the sixty-sixth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JEFCA)." (2006).

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. 2012).

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. 2012; 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. 2012; 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. 2012):

"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. 2012)

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. 2012) 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. 2012).


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. 2012 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 2012. < http://newsinhealth.nih.gov/issue/feb2012/feature1 > retreived Oct 02, 2012.
• 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. 2012 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. 2012 Aug;96(2):382-90.

Food is Medicine: Each 10g Fiber Reduce Mortality Risk by up to 34%! Phenols Battle Alzheimer's & Breast Cancer & Two Dozen Dietary GLUT4 Boosters Prevent Diabetes

Hippocrates says: "Let food be thy medicine!" And he was right. Tons of food contain substances that would make pharmacologist proud and filthy rich if he invented and patented them.

"Let food be thy medicine" Who said that... ha? Right. Hippocrates. He also said "... and let medicine be thy food." Well, he said it in Greek, but that doesn't make the last part less questionable. I do after all often get emails with "supplement lists" that look as if people would be eating nothing else but medicine. Since this would be a topic for another article, though I will postpone the scolding and get straight to the former part of the Hippocrates quote: "Let food be thy medicine!"

If you subscribe to the old Greek's principle, you should also subscribe to the scientific journal Molecular Nutrition & Food Research a journal "devoted to health, safety and all aspects of molecular nutrition such as nutritional biochemistry, nutrigenomics and metabolomics aiming to link the information arising from related disciplines" (from the journal homepage) - quite an interesting journal as you are about to see in a minute or two.

Read more short news at the SuppVersity

Exercise Research Uptake Nov '14 1/2

Exercise Research Uptake Nov '14 2/2

Weight Loss Supplements Exposed

Exercise Supplementation Quickie

Skipping Break- fast & More to Control Weight

HIIT, Caffeine & Other Success Boosters

Why? Well, all the "food is medicine" news in today's installments of the short news come from the latest issue of said journal:

• The beneficial properties of marine polysaccharides in alleviation of allergic responses (Vo. 2014) - Recently, several marine polysaccharides such alginate, porphyran, fucoidan, and chitin and its derivatives have been evidenced as downregulators of allergic responses due to enhancement of innate immune system, alteration of Th1/Th2 balance forward to Th1 cells, inhibition of IgE production, and suppression of mast cell degranulation.
  
  In their recent review, the scientist from the Pukyong National University in Korea thus focus on the antiallergic properties of marine polysaccharides and emphasizes their potential application as bioactive food ingredients as well as nutraceuticals for prevention of allergic disorders.
  

  

  Table 1: Marine polysaccharides for downregulation of allergic responses (Vo .2014).

  What they came up with is the above tabular overview of "marine polysaccharides for downregulation of allergic responses" and the conclusion that it should be possible to produce "a variety of chemically modified derivatives" of the previously mentioned agents that are even more versatile biomaterials which can be used in "almost all fields of biomedical interest" (Vo. 2014).
• Fiber consumption and all-cause, cardiovascular, and cancer mortalities: A systematic review and meta-analysis of cohort studies (Liu. 2014) -  Scientist from the Chinese PLA General Hospital conducted a meta-analysis aimed to investigate fiber consumption and all-cause mortality, and cause-specific mortality.
  
  What they found, when they scanned MEDLINE and web of science database for cohort studies published from inception to August 2014 was a that, compared with those who consumed lowest fiber, for individuals who ate highest fiber,...
  
  • mortality rate was lower by 23% (HR, 0.77; 95% CI, 0.72–0.81) for CVD,
  • by 17% (HR, 0.83; 95% CI, 0.74–0.91) for cancer, and
  • by 23% (HR, 0.77; 95% CI, 0.73–0.81) for all-cause mortality.
  Furthermore, for each 10 g/day increase in fiber intake, the pooled hazard ratio was estimated to be 0.89 (95% CI, 0.86–0.93) for all-cause mortality, 0.80 (95% CI, 0.72–0.88) for CHD mortality, and 0.66 (95% CI, 0.40–0.92) for IHD mortality, 0.91 (95% CI, 0.88–0.94) for cancer.
  

  

  Figure 1: Reduction in mortality risks with every 10g of extra fiber you eat per day (Liu. 2014).

  In plain English: If you eat an extra 10g of fiber per day this will lead to a 11%, 20% and 34% reduction in all-cause mortality, cardiovascular heart disease and ischemic heart disease mortality. Impressed? Rightly so. I mean, as the scientists point out, it's ovious that "fiber consumption is inversely associated with all-cause mortality and CVD, IHD, cancer mortality" (Liu. 2014). What? No, the type of fiber did not appear to materially modify the inverse association between fiber intake and mortality. So you don't have to gobble down allegedly healthy wheat bran ;-)
• The perspective on cholesterol lowering mechanisms of probiotics (Ishimwe. 2014) - The use of probiotics as food components combats not only cardiovascular diseases but also many gastrointestinal tract disorders.
  
  

  

  Figure 2: Enterohepatic circulation of cholesterol and its regulation (Ishimwe. 2014).

  Their health benefits along with their increased global market have interested scientists for better formulation and appropriate administration to the consumers. However, the lack of clear elucidation of their cholesterol-lowering mechanisms has complicated their proper dosage and administration to the beneficiaries. In their recent review, researchers from the Jiangnan University in China propose a mechanisms that would explain why probiotics can reduce the levels of cholesterol in your blood.
  
  Said mechanism involves the deconjugation of bile via bile salt hydrolase activity, binding of cholesterol to probiotic cellular surface and the incorporation into their cell membrane, as well as the production of SCFAs from oligosaccharides, coprecipitation of cholesterol with deconjugated bile, and cholesterol conversion to coprostanol (see Figure 2 | if you are not interested in how it works, check out Table 2 for what happens ;-).
  

  

  Table 2: Interventional human trials of probiotics with effect on serum TC and LDL-C (Ishimwe. 2014).

  And the list of scientifically proven probiotics with cholesterol lowering properties is long. Longer than the list of human trials above (Table 2) and long enough to assume that you can hardly pick one that does not have lipid lowering effect: Lactobacillus Acidophilus (Reuteri, Helveticus, Casei, Bulgaricus, Plantarum, Paracasei, Rhamnosus, Jugurti, Delbrueckii, Sporogenes, Fermentum, Gasseri) , Bifidobacterium Lactis (Longum, Bifidum, Animalis, Breve, Animalis, Infentis) , Streptococcus Thermophilus (Lactis, Salivarius) , Enterococcus Faecium, Propionibacterium Freudenreichii, Lactococcus Lactis.

Overall changes in polyphenol content according to types of food processing in Phenol-Explorer (Rothwell. 2014).

Note: Food remains medicine, only if it is not overtly processed. The table on the left hand side is from a recent review of the of the effects of food processing on polyphenol contents. The data is based on a systematic analysis using Phenol-Explorer data and indicates that even domestic cooking of common plant foods causes considerable losses (median RF = 0.45–0.70) of polyphenols.Compared to processing, food storage causes fewer losses, regardless of food or polyphenol (median RF = 0.88, 0.95, 0.92 for ambient, refrigerated, and frozen storage, respectively). For both processing and storage, though, the food under study is often a more important determinant of retention than the process applied.

• Natural polyphenols binding to amyloid - Phenols as Anti-Alzheimer's drugs (Ngoungoure. 2014) - Polyphenols are a large group of phytonutrients found in herbal beverages and foods. They have manifold biological activities, including antioxidative, antimicrobial, and anti-inflammatory properties. Interestingly, some polyphenols bind to amyloid and substantially ameliorate amyloid diseases.
  

  "Misfolding, aggregation, and accumulation of amyloid fibrils in tissues or organs leads to a group of disorders, called amyloidoses. Prominent diseases are Alzheimer's, Parkinson's, and Huntington's disease, but there are other, less well-known diseases wherein accumulation of misfolded protein is a prominent feature. Amyloidoses are a major burden to public health. In particular, Alzheimer's disease shows a strong increase in patient numbers. Accelerated development of effective therapies for amyloidoses is a necessity. A viable strategy can be the prevention or reduction of protein misfolding, thus reducing amyloid build-up by restoring the cellular aggretome" (Ngoungoure. 2014).

  Amyloid-binding polyphenols affect amyloid formation on various levels, e.g. by inhibiting fibril formation or steering oligomer formation into unstructured, nontoxic pathways. Consequently, preclinical studies demonstrate reduction of amyloid-formation by polyphenols - polypenols you all know very well, curcumin from tumeric, baicalein from the roots of Baikal skullcap, EGCG from green tea, ferulic acid from, among others, coffee, apple, artichoke, peanut, and oranges, and, last but not least, silibinin from milk thistle (see Table 3).
  

  

  Table 3: Preclinicals studies with some amyloid-binding polyphenols (Ngoungoure. 2014).

  As the researchers point out, these studies clearly suggest that the "[i]ntake of dietary polyphenols might be relevant to the prevention of amyloidoses" and that "[n]utraceutical strategies might be a way to reduce amyloid diseases" (Ngoungoure. 2014).
• Breast cancer chemoprevention by dietary natural phenolic compounds (Pan. 2014) - The scientists summarized the misery with breast cancer so perfectly that I will just cite what Pan et al. wrote about breast cancer being "a systemic malignant disease that is a major cause of cancer-related death among women worldwide."
  

  "Recently, multiple lines of evidence from epidemiologic studies have suggested that epigenetic and genetic changes are involved in breast cancer development. In breast cancer patients, hormone receptor status, breast cancer stem-like cell population, and tumor microenvironment are reflective of breast cancer progression, drug resistance, and tumor recurrence. Strong relationships between a phytochemical-rich diet and a reversal of epigenetic alterations and/or modulated signaling pathways of carcinogenesis (initiation, promotion, and progression) suggest a potential approach for preventing breast cancer" (Pan. 2014).

  Next to simply eating healthy and getting all those beneficial phenolic compounds from the diets, there is obviously the potential of supplementing which compounds containing phytoestrogen properties of which we suspect that they will have beneficial effects in breast cancer chemoprevention.
  

  

  Figure 3: . Schematic representation of chemopreventive molecular targets and efficiency of dietary natural phenolic compounds during multiple stages of breast carcinogenesis (Pan. 2014).

  In their review, the researchers from the National Taiwan University summarize the specific chemopreventive targets of representative phenolic compounds with an emphasis on their efficacy at interfering with epigenetic event related hormonal and nonhormonal signaling cascades that are responsible for multistage breast carcinogenesis.
  
  The list they came up with is extensive and includes among others Apigenin from Parsley Celery, Luteolin Spinach Kale, Chrysin Passion flower Honeycomb, Flavonols from Sources, Quercetin from Apple Onion, Kaempferol from Broccoli Tea, Flavanones from Sources, Hesperetin from Orange peel, Naringenin from Orange peel, Flavan-3-ols from Sources, EGCG from Green tea, TF-1 & TF-2 from Black tea, Anthocyanidins from Sources, Delphinidin from Black currants Bilberries, Cyanidin from Cherries, Peonidin from Bilberries, Pelargonidin from Strawberries, Malvidin from Blueberries, Petunidin from Cowpeas, Isoflavones from Sources, Genistein from Soybeans Psoralea, Equol from Soybeans Stinky tofu, Biochanin A from Alfalfa sprouts, Formononetin from Red clover, and Calycosin from Radix Astragali, as well as the following non-flavenoid compounds: Coumestrol from Soy, Curcumin from Turmeric, Garcinol from Garcinia indica, Resveratrol from Grapes Red wine, Pterostilbene from Blueberries, and 6-Shogaol from Ginger.
  
  Needless to say that you don't have to eat / supplement with all of them, but maybe you keep one of the other food source in mind and check how often you are eating (or drinking) it in the months to come ;-)
• Dietary stimulators of GLUT4 expression and translocation in skeletal muscle (Gannon. 2014) - As a SuppVersity reader you know that agents like alpha lipoic acid can increase the expression of glucose receptors (GLUT-4) and thus increase the transport of glucose from the blood into the cells.
  
  In their latest review of the literature, researchers from the University of New Mexico compiled a list of these dietary chemicals of which the researchers say that they may serve "as potential adjuvant therapies in the maintenance of diabetes and insulin resistance" (Gannon. 2014).
  
  • Fucoxanthin
  • Ferulic acid
  • Gingerol
  • Lipoic acid
  • Naringenin
  • Nitric oxide and precursors
  • PPAG
  • PQQ
  • Propolis
  • Quercetin
  • Resveratrol
  • Safranal
  • Synephrine
  • Vanillic acid
  • Agmatine
  • Arecoline
  • Arginine
  • Angelica keiskei extract
  • Astaxanthin
  • Caffeine
  • Chlorogenic acid
  • Cinnamon and extracts
  • Anacardium occidentale nut extract
  • Curcumin
  • Daidzein
  • 10-Hydroxy-2-decenoic acid
  • EGCG
  • EPA/DHA
  • Eugenol
  The above list , which ranges from the purported pump supplement agmatine to vanillic acid, the main active ingredient in the root of Angelica sinensis, has yet to be regarded with caution. Most of the agents have been studies in in vitro studies; and whether the oral consumption of reasonable amounts of the respective agents will have similar beneficial effects remains to be elucidated.

You want even more natural medicine? What about the natural food color betanine? Studies suggest that betanin is a scavenger of reactive oxygen species and exhibits gene-regulatory activity. It may also prevent LDL oxidation and DNA damage and has potential blood pressure lowering effects. That's at least what scientists from the University of Kiel in Germany write in their latest paper (Esatbeyoglu. 2014).

SuppVersity Suggested Read on the Ergogenic and thus the Good Effects of Nitrates: The Beat Your Personal Bests W/ Beets 101: How Much? 8.4 mmol Nitrate ~400-1300g Beets! When? 2.5h Pre Workout | read more

Speaking of food colors or rather additives, one of the most controversial of these are nitrates and nitrites, from which potentially carcinogenic N-nitroso compounds (NOC) can be formed in humans. That's bad news. On the other hand, the consumption of nitrate (which forms nitrate in the gut) and nitrate have been associated with a plethora of health benefits including reductions in blood pressure and heart disease risk (Clifton. 2014; Kapil. 2014; Zamani. 2014).

In a recent review scientists from the University of Kaiserslautern and other German institutions try to identify gaps in our knowledge about the beneficial and ill health effects of dietary nitrate/nitrite intake and come to the conclusion that the existing epidemiological evidence regarding the role of endogenous NOC formation for human cancer risk is inconsistent.

The beneficial effects of the consumption of nitrate-rich fruits and vegetables, on the other hand, are indisputable | Comment on Facebook!

References:

• Clifton, Peter M., et al. "How do fruit and vegetables prevent heart disease and type 2 diabetes?." Current opinion in lipidology 25.2 (2014): 155-156.
• Esatbeyoglu, Tuba, et al. "Betanin—A food colorant with biological activity." Molecular nutrition & food research (2014). 
• Gannon, Nicholas P., Carole A. Conn, and Roger A. Vaughan. "Dietary stimulators of GLUT4 expression and translocation in skeletal muscle: A mini‐review." Molecular nutrition & food research (2014).
• Habermeyer, Michael, et al. "Nitrate and nitrite in the diet: How to assess their benefit and risk for human health." Molecular nutrition & food research (2014).
• Ishimwe, Nestor, et al. "The perspective on cholesterol lowering mechanisms of probiotics." Molecular nutrition & food research (2014). 
• Kapil, Vikas, et al. "Dietary Nitrate Provides Sustained Blood Pressure Lowering in Hypertensive Patients A Randomized, Phase 2, Double-Blind, Placebo-Controlled Study." Hypertension (2014): HYPERTENSIONAHA-114.
• Liu, Lihua, Shan Wang, and Jianchao Liu. "Fiber consumption and all‐cause, cardiovascular, and cancer mortalities: A systematic review and meta‐analysis of cohort studies." Molecular nutrition & food research (2014). 
• Ngoungoure, Viviane L. Ndam, et al. "Natural polyphenols binding to amyloid: A broad class of compounds to treat different human amyloid diseases." Molecular nutrition & food research (2014). 
• Pan, Min‐Hsiung, et al. "Breast cancer chemoprevention by dietary natural phenolic compounds: Specific epigenetic related molecular targets." Molecular nutrition & food research (2014).
• Rothwell, Joseph A., et al. "Effects of food processing on polyphenol contents: A systematic analysis using Phenol‐Explorer data." Molecular nutrition & food research (2014).
• Vo, Thanh‐Sang, et al. "The beneficial properties of marine polysaccharides in alleviation of allergic responses." Molecular nutrition & food research (2014). 
• Zamani, Payman, et al. "The Effect of Inorganic Nitrate on Exercise Capacity in Heart Failure with Preserved Ejection Fraction." Circulation (2014): CIRCULATIONAHA-114.