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.

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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.