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"Too Fat" Part Three!...

This is a continuation of the topic "Too Fat" Part Two!....

Pro and Con

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1margd
Edited: Sep 17, 2017, 8:34am Top

High Prevotella: Bacterioides ratio correlates to weight loss on high fiber diet:

Will You Lose Weight? Take A Look At Your Poop
Bruce Y. Lee

...Researchers from the University of Copenhagen, the Technical University of Denmark, the Steno Diabetes Center Copenhagen, and Gelesis Inc. measured and calculated the ratio of two bacteria, Prevotella and Bacteroides, in the poop from 62 people who were overweight. Then, the researchers randomly assigned the study participants to receive for 26 weeks either the ad libitum New Nordic Diet (NND), which high in fiber and wholegrains, or an Average Danish Diet (ADD).

The results? Among those with a high Prevotella to Bacteroides ratio, study participants on the high fiber (or NND) diet lost on average 3.15 kg (or 6.94 pounds) more body fat than those on the average Danish diet. By contrast, the two diets did not result in any significant difference among those with low Prevotella to Bacteroides ratios. In other words, different bacteria, different responses to the diet.

...Oh, poo, you may say, what if you are stuck with a "bad" microbiome? Well, evidence suggests that different things that you put in your mouth can affect your microbiome such as medications (especially antibiotics) and the food that you eat. Your surroundings such as pollution may also influence your microbiome composition. Although more research is needed to determine how exactly your diet and other factors may affect the bacteria in your intestines and how interventions such as probiotics may help, minimizing antibiotic use is one thing you may want to do immediately...

https://www.forbes.com/sites/brucelee/2017/09/16/will-you-lose-weight-take-a-look-at-your-poop/#285aa5a2576b

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M F Hjorth et al. 2017. Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention. International Journal of Obesity accepted article preview 8 September 2017; doi: 10.1038/ijo.2017.220 . http://www.nature.com/ijo/journal/vaop/naam/abs/ijo2017220a.html?foxtrotcallback...

Abstract. Based on the abundance of specific bacterial genera, the human gut microbiota can be divided into two relatively stable groups that might play a role in personalized nutrition. We studied these simplified enterotypes as prognostic markers for successful body fat loss on two different diets. A total of 62 participants with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in fiber/wholegrain or an Average Danish Diet (ADD) for 26 weeks. Participants were grouped into two discrete enterotypes by their relative abundance of Prevotella spp. divided by Bacteroides spp. (P/B ratio) obtained by quantitative PCR analysis. Modifications of dietary effects of pre-treatment P/B group were examined by linear mixed models. Among individuals with high P/B the NND resulted in a 3.15 kg (95%CI 1.55;4.76, P...) larger body fat loss compared to ADD whereas no differences was observed among individuals with low P/B (0.88 kg 95% CI −0.61;2.37, P...). Consequently, a 2.27 kg (95%CI 0.09;4.45, P...) difference in responsiveness to the diets were found between the two groups. In summary, subjects with high P/B-ratio appeared more susceptible to lose body fat on diets high in fiber and wholegrain than subjects with a low P/B-ratio.

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New Nordic Diet:

...Rich in plant foods (often foraged), the diet includes lots of root vegetables, cabbage (and other crucifers), dark greens, apples and pears, berries (such as ligonberries and bilberries) and whole grains (such as rye and oats). Fish (such as salmon and herring) is also prominent, along with some wild game (such as elk, inherently low in fat) and small amounts of dairy. Other wild foods include moss, mushrooms, nettles, garlic and even ants. Fresh herbs include dill, chives and fennel. For dessert, how about some barley pudding?

In many ways, the New Nordic Diet is very similar to a Mediterranean diet but relies on rapeseed (canola) oil instead of olive oil and differs in its types of produce (few tomatoes here), simply as a reflection of what the region’s climate, soil and water naturally—and best—produce...

http://www.berkeleywellness.com/healthy-eating/diet-weight-loss/article/new-nord...

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A Paleo afficionado ponders relationships among Prevotella, meat & other foods, whole grain consumption, TMAO, atherosclerosis...

http://humanfoodproject.com/from-meat-to-microbes-to-main-street-is-it-time-to-t...

2margd
Sep 28, 2017, 9:31am Top

Greta Lazutkaite et al. 2017, Amino acid sensing in hypothalamic tanycytes via umami taste receptors. Molecular Metabolism.
DOI: http://dx.doi.org/10.1016/j.molmet.2017.08.015 | http://www.molmetab.com/article/S2212-8778(17)30537-9/abstract

...4.2. Similarities between tanycytes and taste receptor cells

...The detection of circulating nutrients by tanycytes, thus, is remarkably similar to that of taste sensing in the tongue both in the types of receptors involved and the consequent downstream signaling via channel-mediated release of ATP. Thus, tanycytes should be thought of as general nutrient sensors in the hypothalamus.

4.3. Amino acid detection in the brain

...Our discovery that tanycytes also sense amino acids in the CSF (cerebrospinal fluid) via at least two receptors is an important advance that suggests: 1) that tanycytes are anorexigenic; and 2) that they might act with the neural networks in the hypothalamus to regulate food intake...

5. Conclusions

Hypothalamic tanycytes are directly sensitive to a range of essential and non-essential amino acids, which are important signals of satiety...Our data warrant investigation as to whether tanycytes may be physiological mediators of satiety signals and act to reduce food intake.

______________________________________

Chicken, plums and lentils make you fuller quicker, study claims
The foods that just got healthier
Olivia Petter | 28 September 2017

...Apricots, plums, almonds, lentils and pork shoulder, chicken, sirloin steak, avocadoes and almonds all boast high concentrations of amino acids and therefore make people feel fuller quicker than other foods.

...Dr Nicholas Dale, Professor of Neuroscience at the university (of Warwick)...“Finding that tanycytes, located at the centre of the brain region that controls body weight, directly sense amino acids has very significant implications for coming up with new ways to help people to control their body weight within healthy bounds.”

Dale and his team came across the effect after they directly added a high dosage of amino acids into the brain.

The tanycytes responded just thirty seconds later, sending signals to the brain that manages appetite and would stimulate feelings of fullness.

The findings could be key in developing appetite-suppressants...

http://www.independent.co.uk/life-style/food-and-drink/chicken-plums-lentils-fil...

3margd
Oct 4, 2017, 11:53am Top

Both black and green tea reduce weight in mice fed high fat diet, but some difference in mechanisms:

Susanne M. Henning et al. 2017. Decaffeinated green and black tea polyphenols decrease weight gain and alter microbiome populations and function in diet-induced obese mice. Eur J Nutr (2017). https://doi.org/10.1007/s00394-017-1542-8 . https://link.springer.com/article/10.1007/s00394-017-1542-8

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Tea Aids Weight Loss through Microbiome Alteration
October 4, 2017

...investigators at UCLA have demonstrated that tea, and in particular black tea, may promote weight loss and other health benefits by changing bacteria within the gut. Findings from the new study...show that in mice black tea alters energy metabolism in the liver by changing gut metabolites.

"It was known that green tea polyphenols (GTPs) are more effective and offer more health benefits than black tea polyphenols (BTPs) since green tea chemicals are absorbed into the blood and tissue," explained lead study investigator Susanne Henning, Ph.D., an adjunct professor at the UCLA Center for Human Nutrition, which is part of the David Geffen School of Medicine at UCLA. "Our new findings suggest that black tea, through a specific mechanism through the gut microbiome, may also contribute to good health and weight loss in humans."

Interestingly, the study found that both black and green tea changed the ratio of intestinal bacteria in the animals: The percentage of bacteria associated with obesity decreased, while bacteria associated with lean body mass increased.

"The results suggest that both green and black teas are prebiotics, substances that induce the growth of good microorganisms that contribute to a person's well-being," Dr. Henning noted.

Previous studies have indicated that chemicals in green tea called polyphenols are absorbed and alter the energy metabolism in the liver. The new findings show that BTPs, which are too large to be absorbed in the small intestine, stimulate the growth of gut bacterium and the formation of short-chain fatty acids, a type of bacterial metabolites that have been shown to alter the energy metabolism in the liver.

In the current study, four groups of mice received different diets—two of which were supplemented with green tea or black tea extracts:

· Low-fat, high-sugar;

· High-fat, high-sugar;

· High-fat, high-sugar and green tea extract;

· High-fat, high-sugar and black tea extract.

Amazingly, the research team found that after four weeks the weights of the mice that were given green or black tea extracts dropped to the same levels as those of the mice that received the low-fat diet throughout the study. Moreover, the investigators collected samples from the mice's large intestines (to measure bacteria content) and liver tissues (to measure fat deposits). In the mice that consumed either type of tea extract, there was less of the type of bacteria associated with obesity and more of the bacteria associated with lean body mass.

However, only the mice that consumed black tea extract had an increase in a type of bacteria called Pseudobutyrivibrio, which could help explain the difference between how black tea and green tea change energy metabolism.

...The researchers noted that these new findings suggest the health benefits of both green tea and black tea go beyond their antioxidant benefits and that both teas have a strong impact on the gut microbiome.

"For black tea lovers, there may be a new reason to keep drinking it," concluded senior study investigator Zhaoping Li, M.D., director of the UCLA Center for Human Nutrition and chief of the UCLA Division of Clinical Nutrition.

http://www.genengnews.com/gen-news-highlights/tea-aids-weight-loss-through-micro...

42wonderY
Oct 4, 2017, 12:45pm Top

>3 margd: And I read recently that high fructose corn syrup increases the fat storage in the liver.

My daughter has switched from sodas to tea (black tea mostly, and all day long) and her weight is going down while her energy levels increase. It has made a remarkable difference in her life.

Nice to know some of the background biochemistry.

5margd
Oct 19, 2017, 10:40am Top

(My brainstem made me eat that IC! :-)

Scientists engineer proteins that caused obese animals to lose weight and lower cholesterol
Melissa Healy | Oct 19, 2017

...Scientists from the biotechnology company Amgen Inc. report they have identified and improved upon a naturally occurring protein that brought about significant changes in obese mice and monkeys, including weight loss and rapid improvements on measures of metabolic and heart health.

...In mice who got a bioengineered version of the GDF15 protein, the researchers observed even more remarkable changes. These obese mice turned their noses up at extra-rich condensed milk — a treat that normally prompts mice to gorge themselves. Given the choice, the treated mice tended to opt for standard mouse chow instead, or at least lowered their intake of the fattening condensed milk.
Nearly 4 in 10 U.S. adults are now obese, CDC says

After 35 days, obese mice treated with the bioengineered GDF15 proteins lost roughly 20% of their body weight, while mice getting a placebo gained about 6% over their starting weight, according to the study. When mice were offered the rich condensed milk, triglyceride levels remained at baseline or rose by about 20% in those who got the engineered proteins, while levels more than doubled in the untreated mice. Insulin levels and total cholesterol readings were also significantly better in treated animals than in their untreated counterparts.

The results suggest that the GDF15 engineered by researchers had the power to turn off the kind of reward-driven eating (think doughnuts, milkshakes or bacon cheeseburgers) that drives many of us to become obese, or to regain lost weight.

...In the brains of the lab animals that received the treatment, the study authors detected activation in a population of brain-stem cells that transmits complex signals between the brain and gut.

In obese people, those signals — which urge us to eat when we’re hungry and to stop once we’ve eaten — become faulty, causing us to overeat and gain weight. Bariatric surgery appears to correct those signals.

So the suggestion that GDF15 might do the same is an exciting indication that a piece of bariatric surgery’s magic might be bottled up in a pill...

http://www.latimes.com/science/sciencenow/la-sci-sn-weight-loss-protein-20171019...

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Yumei Xiong et al. 2017. Long-acting MIC-1/GDF15 molecules to treat obesity: Evidence from mice to monkeys. See all authors and affiliations
Science Translational Medicine 18 Oct 2017: Vol. 9, Issue 412, eaan8732 . DOI: 10.1126/scitranslmed.aan8732 . http://stm.sciencemag.org/content/9/412/eaan8732

A bigger molecule to help slim down
Obesity is becoming increasingly common worldwide, and the available interventions do not fully address this problem. Surgery is currently the most effective intervention, especially for severe obesity, but it carries more risks than noninvasive treatments and produces permanent side effects. Xiong et al. searched for metabolically regulated proteins and identified the growth differentiation factor 15 (GDF15) pathway as a potential target for intervention. The loss of this protein in mice is associated with weight gain and worsened metabolic parameters. Conversely, the authors showed that treating with GDF15 improved metabolic health in mice, rats, and monkeys. They also designed a modified version of GDF15 (GDF15-Fc fusion) that has a longer half-life and would thus be a better candidate for clinical testing.

Abstract
In search of metabolically regulated secreted proteins, we conducted a microarray study comparing gene expression in major metabolic tissues of fed and fasted ob/ob mice and C57BL/6 mice. The array used in this study included probes for ~4000 genes annotated as potential secreted proteins. Circulating macrophage inhibitory cytokine 1 (MIC-1)/growth differentiation factor 15 (GDF15) concentrations were increased in obese mice, rats, and humans in comparison to age-matched lean controls. Adeno-associated virus–mediated overexpression of GDF15 and recombinant GDF15 treatments reduced food intake and body weight and improved metabolic profiles in various metabolic disease models in mice, rats, and obese cynomolgus monkeys. Analysis of the GDF15 crystal structure suggested that the protein is not suitable for conventional Fc fusion at the carboxyl terminus of the protein. Thus, we used a structure-guided approach to design and successfully generate several Fc fusion molecules with extended half-life and potent efficacy. Furthermore, we discovered that GDF15 delayed gastric emptying, changed food preference, and activated area postrema neurons, confirming a role for GDF15 in the gut-brain axis responsible for the regulation of body energy intake. Our work provides evidence that GDF15 Fc fusion proteins could be potential therapeutic agents for the treatment of obesity and related comorbidities.

6margd
Oct 23, 2017, 2:41am Top

In mice, suspected association between gut fungi and obesity:

Gut fungi might be linked to obesity...
Yeast and bacteria can team up to cause trouble
Tina Hesman Saey | October 16, 2017

...High-fat diets may alter relationships between bacteria and fungi in mice’s intestines, contributing to obesity, researchers report October 11 in mSphere.

Cheryl Gale of the University of Minnesota in Minneapolis...fed mice either standard mouse chow or high-fat chow. As expected, mice on the high-fat diet gained weight, and the mix of bacteria in their guts shifted. Firmicutes bacteria associated with obesity increased, while Bacteroidetes bacteria decreased in abundance.

Fungi changed too. Mice fed high-fat chow had less Saccharomyces cerevisiae yeast and more Candida albicans in their guts than did mice that ate standard chow. S. cerevisiae is a yeast used in making wine, beer and bread and has been associated with good health. C. albicans is an organism that causes many yeast infections.

Gale’s team also discovered that relationships between bacteria and fungi changed when mice’s diets were changed. Her team can’t yet show a direct connection between the composition of gut fungi and obesity, but suspects that shifting interactions between bacteria and fungi might lead the host to gain weight...

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T. Heisel et al. High-fat diet changes fungal microbiomes and interkingdom relationships in the murine gut. mSphere. Vol. 2, October 11, 2017, p. e00351. doi: 10.1128/mSphere.00351-17 . http://msphere.asm.org/content/2/5/e00351-17

ABSTRACT

Dietary fat intake and shifts in gut bacterial community composition are associated with the development of obesity. To date, characterization of microbiota in lean versus obese subjects has been dominated by studies of gut bacteria. Fungi, recently shown to affect gut inflammation, have received little study for their role in obesity. We sought to determine the effects of high-fat diet on fungal and bacterial community structures in a mouse model using the internal transcribed spacer region 2 (ITS2) of fungal ribosomal DNA (rDNA) and the 16S rRNA genes of bacteria. Mice fed a high-fat diet had significantly different abundances of 19 bacterial and 6 fungal taxa than did mice fed standard chow, with high-fat diet causing similar magnitudes of change in overall fungal and bacterial microbiome structures. We observed strong and complex diet-specific coabundance relationships between intra- and interkingdom microbial pairs and dramatic reductions in the number of coabundance correlations in mice fed a high-fat diet compared to those fed standard chow. Furthermore, predicted microbiome functional modules related to metabolism were significantly less abundant in high-fat-diet-fed than in standard-chow-fed mice. These results suggest a role for fungi and interkingdom interactions in the association between gut microbiomes and obesity.

7margd
Nov 2, 2017, 5:19am Top

Osteocalcin produced in bone, activated by enzyme furin, has role in fat and sugar metabloism.
(Vitamin K also has function, I think, but what I'm not sure--paper lost me in Introduction...)

The weight loss secret to metabolising fat and sugar is in your bones
Paloma Sharma | Nov 2, 2017

...According to new study from Canada’s Montreal Clinical Research Institute (IRCM), your bones may hold the key to help you lose weight, keep off the fat and even prevent Type 2 diabetes – all due to a hormone called osteocalcin. Produced by the bones themselves, osteocalcin affects your appetite as well as your body’s ability to metabolise sugar and fat. The director of the Integrative and Molecular Physiology Research Unit at the IRCM, Dr Mathieu Ferron, was quoted by Bioscience Technology explaining how the discovery of this hormone and its functions could aid in making humankind a fitter species, “Osteocalcin helps, among other things, to produce insulin, which lowers the level of glucose in our blood. It could also protect us from obesity by increasing our energy expenditure. ”

Produced by single nucleus cells called osteoblasts, which are responsible for bone building, osteocalcin alone cannot help regulate sugar levels within the body. When osteocalcin is first produced through osteoblasts during the bone formation process, it is inactive. Researchers found that it needs to be acted upon by furin, a cellular endoproteinase, for it to transform into active osteocalcin – which is then released into the body’s blood stream, where it begins its work...

https://www.gqindia.com/content/weight-loss-metabolism-bones/
__________________________________________________​

Omar Al Rifai et al. 2017. Proprotein convertase furin regulates osteocalcin and bone endocrine function. J Clin Invest. 2017;127(11):4104-4117. doi:10.1172/JCI93437. https://www.jci.org/articles/view/93437/pdf

Abstract. Osteocalcin (OCN) is an osteoblast-derived hormone that increases energy expenditure, insulin sensitivity, insulin secretion,
and glucose tolerance. The cDNA sequence of OCN predicts that, like many other peptide hormones, OCN is first synthesized
as a prohormone (pro-OCN). The importance of pro-OCN maturation in regulating OCN and the identity of the endopeptidase
responsible for pro-OCN cleavage in osteoblasts are still unknown. Here, we show that the proprotein convertase furin is
responsible for pro-OCN maturation in vitro and in vivo. Using pharmacological and genetic experiments, we also determined
that furin-mediated pro-OCN cleavage occurred independently of its γ-carboxylation, a posttranslational modification that
is known to hamper OCN endocrine action. However, because pro-OCN is not efficiently decarboxylated and activated during
bone resorption, inactivation of furin in osteoblasts in mice resulted in decreased circulating levels of undercarboxylated OCN,
impaired glucose tolerance, and reduced energy expenditure. Furthermore, we show that Furin deletion in osteoblasts reduced
appetite, a function not modulated by OCN, thus suggesting that osteoblasts may secrete additional hormones that regulate
different aspects of energy metabolism. Accordingly, the metabolic defects of the mice lacking furin in osteoblasts became more
apparent under pair-feeding conditions. These findings identify furin as an important regulator of bone endocrine function.

Introduction...γ-Carboxylation of OCN (osteocalcin) occurs in the ER (Endoplasmic Reticulum??) and is mediated by γ-glutamyl carboxylase (GGCX), which requires reduced vitamin K as an essential cofactor (10). ... Here, we identified furin, using cell-based and genetic arguments, as the endopeptidase responsible for pro-OCN (osteocalcin) processing in osteoblasts. We also showed in cell culture and in vivo that γ-carboxylation and processing of OCN are 2 independent processes in osteoblasts. The study of mice lacking furin specifically in osteoblasts revealed that proteolysis of pro-OCN is critical for the activation of this hormone. We also found that furin may modulate energy metabolism through OCN-independent pathway(s) affecting appetite...

...10. Stafford DW. The vitamin K cycle. J Thromb Haemost. 2005;3(8):1873–1878....

8margd
Nov 23, 2017, 5:25am Top

Cinnamon's essential oil that gives cinnamon its flavor, (cinnamaldehyde), "improves metabolic health by acting directly on fat cells, or adipocytes, inducing them to start burning energy through a process called thermogenesis."

Juan Jiang et al. 2017. Cinnamaldehyde induces fat cell-autonomous thermogenesis and metabolic reprogramming. Metabolism. December 2017Volume 77, Pages 58–64 . DOI: http://dx.doi.org/10.1016/j.metabol.2017.08.006 . http://www.metabolismjournal.com/article/S0026-0495(17)30212-3/fulltext

Conclusions. CA activates thermogenic and metabolic responses in mouse and human primary subcutaneous adipocytes in a cell-autonomous manner, giving a mechanistic explanation for the anti-obesity effects of CA observed previously and further supporting its potential metabolic benefits on humans. Given the wide usage of cinnamon in the food industry, the notion that this popular food additive, instead of a drug, may activate thermogenesis, could ultimately lead to therapeutic strategies against obesity that are much better adhered to by participants.

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Cinnamon turns up the heat on fat cells
Emily Kagey | Nov 21, 2017
http://ns.umich.edu/new/releases/25273-cinnamon-turns-up-the-heat-on-fat-cells

9mamzel
Nov 27, 2017, 6:32pm Top

>8 margd: I'm glad to hear this. I put plain cinnamon on my toast every morning (had to cut out sugar). Don't see much in the way of results yet or is this one of those things where you have to ingest huge quantities for the effect to work? (I would read the article but too many words with too many syllables makes my brain rebel. I have no clue what a subcutaneous adipocyte is. A fat cell, maybe?)

10margd
Nov 28, 2017, 4:25am Top

I know what you mean about the jargon!

(Wikipedia on adipose tissue: In humans, adipose tissue is located beneath the skin (subcutaneous fat), around internal organs (visceral fat), in bone marrow (yellow bone marrow), intermuscular (Muscular system) and in the breast tissue...adipocytes...comprise the highest percentage of cells within adipose tissue)

I remember looking for the actionable amount of cinnamon and not finding anything usable--can't access the paper now to look again... :-( One thing I was concerned about is that the info would resurrect recent teen practice of taking cinnamon by the spoonful--I seem to recall one kid died of it (aspiration).

For myself, I use such info as reason to include a food in my diet. Sometimes I keep a checklist of such foods on the fridge, such as MD Michael Greger's Daily Dozen. I'm no vegetarian but the list bends me toward better choices, I hope! He even has a free app! https://nutritionfacts.org/video/dr-gregers-daily-dozen-checklist/

11margd
Dec 29, 2017, 9:46am Top

Evidence found for a body-weight sensor in the long bones of the lower extremities that regulates fat. This New Year--resolve to walk, stand, weight-bearing leg exercises, not ignore Fitbit reminders? ;-)

Scientists Discover an Entirely New Biological System That Regulates Body Fat
Independent of diet and exercise.
DAVID NIELD | 29 DEC 2017

New research has identified a mechanism in the body that appears to act as a kind of internal bathroom scale, registering body weight and telling the brain to reduce or increase food intake as necessary.

..."The weight of the body is registered in the lower extremities. If the body weight tends to increase, a signal is sent to the brain to decrease food intake and keep the body weight constant."

...scientists fitted extra weights to already obese rodents and observed what happened.

When the extra weights were added to the mice, body fat decreased and blood glucose levels improved. In fact, the animals lost the same amount of weight as had been added.

...The precise workings of these internal scales – which have been dubbed the gravitostat – aren't yet clear, but based on follow-up tests the scientists think some of the sensing might be done by the bones lower down in the body.

What appears to be happening is that cells in the mice's bones - known as osteocytes - are somehow detecting the amount of weight and strain on bones, and then feed that message back to the brain....

https://www.sciencealert.com/study-discovers-internal-biological-scales-monitoring-weight

__________________________________________________​-

John-Olov Jansson et al. 2017. Body weight homeostat that regulates fat mass independently of leptin in rats and mice. PNAS doi: 10.1073/pnas.1715687114 . http://www.pnas.org/content/early/2017/12/19/1715687114.full

Significance

The only known homeostatic regulator of fat mass is the leptin system. We hypothesized that there is a second homeostat regulating body weight with an impact on fat mass. In this study we have added and removed weight loads from experimental animals and measured the effects on the biological body weight. The results demonstrate that there is a body weight homeostat that regulates fat mass independently of leptin. As the body weight-reducing effect of increased loading was dependent on osteocytes, we propose that there is a sensor for body weight in the long bones of the lower extremities acting as “body scales.” This is part of a body weight homeostat, “gravitostat,” that keeps body weight and body fat mass constant.

Abstract

Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat (“gravitostat”) that regulates fat mass.

12margd
Jan 7, 2018, 7:21am Top

Soluble fiber supplement reduced BMI, wt (~5lbs), fat, fasting glucose, fasting insulin (Am J Clin Nutr)

The inulin in study is widely available in pharmacies as a generic brand powder. (Made from chicory root.) Some gut conditions aggravated by soluble fiber, so do your homework. Increase gradually in diet, so you don't overstrip your microbiome and cause GIT distress. (I mix another soluble fiber in my coffee every morning (gum Arabic, Heather's).)

Variety of fibers best: fruits & veg, whole grains (like oatmeal), beans, etc. Plus the soluble fiber supplement? http://healthyeating.sfgate.com/sources-soluble-fiber-natural-foods-2125.html Also--probiotics like kefir

NYT article that follows Thomson et al. has great explanation of how fiber feeds microbiome that effects these effects and more:

Sharon V Thomson et al. 2017. Effects of isolated soluble fiber supplementation on body weight, glycemia, and insulinemia in adults with overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. First published November 1, 2017, doi: 10.3945/​ajcn.117.163246. http://ajcn.nutrition.org/content/early/2017/11/01/ajcn.117.163246.abstract

Abstract
Background: There is strong epidemiologic evidence that dietary fiber intake is protective against overweight and obesity; however, results of intervention studies have been mixed. Soluble fiber beneficially affects metabolism, and fiber supplementation may be a feasible approach to improve body composition and glycemia in adults with overweight and obesity.

Objective: We evaluated randomized controlled trials (RCTs) of isolated soluble fiber supplementation in overweight and obese adults on outcomes related to weight management (body mass index (BMI; in kg/m2), body weight, percentage of body fat, and waist circumference)and glucose and insulin metabolism (homeostasis model assessment of insulin resistance and fasting insulin) through a systematic review and meta-analysis.

Design: We searched PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature and Cochrane Library databases. Eligible studies were RCTs that compared isolated soluble fiber with placebo treatments without energy-restriction protocols...

Results: Findings from 12 RCTs (n = 609 participants) from 2 to 17 wk of duration are summarized in this review. Soluble fiber supplementation reduced BMI by 0.84...body weight by 2.52 kg...body fat by 0.41%...fasting glucose by 0.17 mmol/L...and fasting insulin by 15.88 pmol/L... compared with the effects of placebo treatments. No publication bias was identified. Considerable between-study heterogeneity was observed for most outcomes.

Conclusions: Isolated soluble fiber supplementation improves anthropometric and metabolic outcomes in overweight and obese adults, thereby indicating that supplementation may improve fiber intake and health in these individuals. However, the interpretation of these findings warrants caution because of the considerable between-study heterogeneity...

__________________________________________________​

Fiber Is Good for You. Now Scientists May Know Why.
Carl Zimmer | JAN. 1, 2018

A diet of fiber-rich foods, such as fruits and vegetables, reduces the risk of developing diabetes, heart disease and arthritis. Indeed, the evidence for fiber’s benefits extends beyond any particular ailment: Eating more fiber seems to lower people’s mortality rate, whatever the cause.

...But while the benefits are clear, it’s not so clear why fiber is so great.

,,,The ability of these bacteria to survive on fiber we can’t digest ourselves has led many experts to wonder if the microbes are somehow involved in the benefits of the fruits-and-vegetables diet. Two detailed studies published recently in the journal Cell Host and Microbe provide compelling evidence that the answer is yes.

In one experiment, Andrew T. Gewirtz of Georgia State University and his colleagues put mice on a low-fiber, high-fat diet. By examining fragments of bacterial DNA in the animals’ feces, the scientists were able to estimate the size of the gut bacterial population in each mouse.

On a low-fiber diet, they found, the population crashed, shrinking tenfold.

Dr. Bäckhed and his colleagues carried out a similar experiment, surveying the microbiome in mice as they were switched from fiber-rich food to a low-fiber diet. “It’s basically what you’d get at McDonald’s,” said Dr. Bäckhed said. “A lot of lard, a lot of sugar, and twenty percent protein.”

The scientists focused on the diversity of species that make up the mouse’s gut microbiome. Shifting the animals to a low-fiber diet had a dramatic effect, they found: Many common species became rare, and rare species became common.

Along with changes to the microbiome, both teams also observed rapid changes to the mice themselves. Their intestines got smaller, and its mucus layer thinner. As a result, bacteria wound up much closer to the intestinal wall, and that encroachment triggered an immune reaction.

After a few days on the low-fiber diet, mouse intestines developed chronic inflammation. After a few weeks, Dr. Gewirtz’s team observed that the mice began to change in other ways, putting on fat, for example, and developing higher blood sugar levels.

Dr. Bäckhed and his colleagues also fed another group of rodents the high-fat menu, along with a modest dose of a type of fiber called inulin. The mucus layer in their guts was healthier than in mice that didn’t get fiber, the scientists found, and intestinal bacteria were kept at a safer distance from their intestinal wall.

Dr. Gewirtz and his colleagues gave inulin to their mice as well, but at a much higher dose. The improvements were even more dramatic: Despite a high-fat diet, the mice had healthy populations of bacteria in their guts, their intestines were closer to normal, and they put on less weight.

Dr. Bäckhed and his colleagues ran one more interesting experiment: They spiked water given to mice on a high-fat diet with a species of fiber-feeding bacteria. The addition changed the mice for the better: Even on a high-fat diet, they produced more mucus in their guts, creating a healthy barrier to keep bacteria from the intestinal walls.

One way that fiber benefits health is by giving us, indirectly, another source of food, Dr. Gewirtz said. Once bacteria are done harvesting the energy in dietary fiber, they cast off the fragments as waste. That waste — in the form of short-chain fatty acids — is absorbed by intestinal cells, which use it as fuel.

But the gut’s microbes do more than just make energy. They also send messages.

Intestinal cells rely on chemical signals from the bacteria to work properly, Dr. Gewirtz said. The cells respond to the signals by multiplying and making a healthy supply of mucus. They also release bacteria-killing molecules.

By generating these responses, gut bacteria help maintain a peaceful coexistence with the immune system. They rest atop the gut’s mucus layer at a safe distance from the intestinal wall. Any bacteria that wind up too close get wiped out by antimicrobial poisons.

While some species of gut bacteria feed directly on dietary fiber, they probably support other species that feed on their waste. A number of species in this ecosystem — all of it built on fiber — may be talking to our guts.

Going on a low-fiber diet disturbs this peaceful relationship, the new studies suggest. The species that depend on dietary fiber starve, as do the other species that depend on them. Some species may switch to feeding on the host’s own mucus.

With less fuel, intestinal cells grow more slowly. And without a steady stream of chemical signals from bacteria, the cells slow their production of mucus and bacteria-killing poisons.

As a result, bacteria edge closer to the intestinal wall, and the immune system kicks into high gear.

... Among other things, chronic inflammation may interfere with how the body uses the calories in food, storing more of it as fat rather than burning it for energy.

Justin L. Sonnenburg, a biologist at Stanford University who was not involved in the new studies, said that a low-fiber diet can cause low-level inflammation not only in the gut, but throughout the body.

His research suggests that when bacteria break down dietary fiber down into short-chain fatty acids, some of them pass into the bloodstream and travel to other organs, where they act as signals to quiet down the immune system.

Hannah D. Holscher, a nutrition scientist at the University of Illinois... provide(s) volunteers with all their meals for two weeks. She can then give some of her volunteers an extra source of fiber — such as walnuts — and look for changes in both their microbiome and their levels of inflammation.

Dr. Holscher and other researchers hope that they will learn enough about how fiber influences the microbiome to use it as a way to treat disorders. Lowering inflammation with fiber may also help in the treatment of immune disorders such as inflammatory bowel disease.

Fiber may also help reverse obesity. Last month in the American Journal of Clinical Nutrition, Dr. Holscher and her colleagues reviewed a number of trials in which fiber was used to treat obesity. They found that fiber supplements helped obese people to lose about five pounds, on average.

But for those who want to stay healthy, simply adding one kind of fiber to a typical Western diet won’t be a panacea. Giving mice inulin in the new studies only partly restored them to health.

That’s probably because we depend on a number of different kinds of dietary fiber we get from plants. It’s possible that each type of fiber feeds a particular set of bacteria, which send their own important signals to our bodies...

https://www.nytimes.com/2018/01/01/science/food-fiber-microbiome-inflammation.html

13margd
Jan 23, 2018, 8:23am Top

Cilia in the brain may be busier than previously thought
The long-overlooked nerve cell appendage may help prevent obesity or aid communication among cells
Laura Sanders | January 19, 2018

...cilia appear to play a role in preventing obesity, researchers report January 8 in three studies in Nature Genetics

...molecular geneticist Christian Vaisse of the University of California, San Francisco... studied mutations in a protein called MC4R that are known to cause severe obesity in people. Experiments on mice showed that MC4R normally resides within the cilia on appetite-controlling nerve cells. But several of these mutations prevented MC4R from reaching those cells’ cilia from elsewhere in the cells, experiments on cells in dishes showed. And one of these mutations prevented MC4R from reaching nerve cell cilia in the brains of mice.

When the researchers interfered with ADCY3, a protein in the cilia that helps MC4R regulate appetite, the resulting mice became obese. Those results suggest that MC4R must reach the cilia in order to interact with ADCY3 and work properly. In the other two papers, scientists link the ADCY3 gene to obesity in people, providing more evidence that cilia are involved in obesity.

...That link has already been found in rare cases. Mutations that affect cilia can cause severe obesity, as seen with diseases such as Bardet-Biedl syndrome. But the new results hint that abnormal cilia may be more widely involved in obesity. Earlier genetic studies have tied obesity to the MC4R gene, which the mouse study now shows to be important in cilia. It’s possible that many of the common genetic obesity culprits may actually be tinkering with the primary cilia, Vaisse says.

It’s not yet clear why the MC4R protein needs to reach the cilia to control appetite, (Kirk Mykytyn, a cell biologist at Ohio State University College of Medicine in Columbus) says. It’s possible that the appendages possess the right mix of helper proteins that aid MC4R in its job. Or cilia might change the way the protein works, allowing it to be more efficient....

Citations

J.E. Siljee et al. Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity. Nature Genetics. Published online January 8, 2018. doi: 10.1038/s41588-017-0020-9. https://www.nature.com/articles/s41588-017-0020-9.epdf

N. Grarup et al. Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes. Nature Genetics. Published online January 8, 2018. doi:10.1038/s41588-017-0022-7. https://www.nature.com/articles/s41588-017-0022-7.epdf

S. Saeed et al. Loss-of-function mutations in ADCY3 cause monogenic severe obesity. Nature Genetics. Published online January 8, 2018. doi:10.1038/s41588-017-0023-6. https://www.nature.com/articles/s41588-017-0023-6.epdf

...

https://www.sciencenews.org/article/cilia-brain-may-be-busier-previously-thought

14margd
Feb 20, 2018, 3:48pm Top

Counting Calories Is Not the Key to Weight Loss, New Study Finds
ANAHAD O’CONNOR | FEB. 20, 2018

...a new study, published Tuesday in JAMA...found that people who cut back on added sugar, refined grains and highly processed foods while concentrating on eating plenty of vegetables and whole foods — without worrying about counting calories or limiting portion sizes — lost significant amounts of weight over the course of a year.

The strategy worked for people whether they followed diets that were mostly low in fat or mostly low in carbohydrates. And their success did not appear to be influenced by their genetics or their insulin-response to carbohydrates, a finding that casts doubt on the increasingly popular idea that different diets should be recommended to people based on their DNA makeup or on their tolerance for carbs or fat.

The research lends strong support to the notion that diet quality, not quantity, is what helps people lose and manage their weight most easily in the long run. It also suggests that health authorities should shift away from telling the public to obsess over calories and instead encourage Americans to avoid processed foods that are made with refined starches and added sugar, like bagels, white bread, refined flour and sugary snacks and beverages

...Soft drinks, fruit juice, muffins, white rice and white bread are technically low in fat, for example, but the low-fat group was told to avoid those things and eat foods like brown rice, barley, steel-cut oats, lentils, lean meats, low-fat dairy products, quinoa, fresh fruit and legumes. The low-carb group was trained to choose nutritious foods like olive oil, salmon, avocados, hard cheeses, vegetables, nut butters, nuts and seeds, and grass-fed and pasture-raised animal foods.

...While people on average lost a significant amount of weight in the study, there was also wide variability in both groups. Some people gained weight, and some lost as much as 50 to 60 pounds. Dr. Gardner said that the people who lost the most weight reported that the study had “changed their relationship with food.” They no longer ate in their cars or in front of their television screens, and they were cooking more at home and sitting down to eat dinner with their families, for example.

... the new study found that after one year of focusing on food quality, not calories, the two groups lost substantial amounts of weight. On average, the members of the low-carb group lost just over 13 pounds, while those in the low-fat group lost about 11.7 pounds. Both groups also saw improvements in other health markers, like reductions in their waist sizes, body fat, and blood sugar and blood pressure levels.

...focus on that foundational diet, which is more vegetables, more whole foods, less added sugar and less refined grains.”

https://www.nytimes.com/2018/02/20/well/eat/counting-calories-weight-loss-diet-dieting-low-carb-low-fat.html
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Christopher D. Gardner et al. February 20, 2018. Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion. JAMA. 2018;319(7):667-679. doi:10.1001/jama.2018.0245
https://jamanetwork.com/journals/jama/article-abstract/2673150?redirect=true

Key Points

Question What is the effect of a healthy low-fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change at 12 months and are these effects related to genotype pattern or insulin secretion?

Findings In this randomized clinical trial among 609 overweight adults, weight change over 12 months was not significantly different for participants in the HLF diet group (−5.3 kg) vs the HLC diet group (−6.0 kg), and there was no significant diet-genotype interaction or diet-insulin interaction with 12-month weight loss.

Meaning There was no significant difference in 12-month weight loss between the HLF and HLC diets, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss.

15margd
Mar 22, 2018, 9:18am Top

How obesity makes it harder to taste
Inflammation linked to the disease caused the loss of taste buds in mice
Aimee Cunningham | March 20, 2018

...Compared with siblings that were fed normal mouse chow, mice given high-fat meals lost about 25 percent of their taste buds over eight weeks. Buds went missing because mature taste bud cells died off more quickly, and fewer new cells developed to take their place. Chronic, low-level inflammation associated with obesity appears to be behind the loss.

...The taste tissues of the obese mice had a higher amount of a type of protein called a cytokine, which regulates inflammation, than their normal-weight kin...

This particular cytokine, called tumor necrosis factor alpha, seems to be damaging to taste buds...

Citations
A. Kaufman et al. Inflammation arising from obesity reduces taste bud abundance and inhibits renewal. PLOS Biology. Published online March 20, 2018. doi: 10.1371/journal.pbio.2001959. http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2001959

Further Reading
L. Sanders. Obscure brain region linked to feeding frenzy in mice. Science News Online, May 25, 2017. https://www.sciencenews.org/article/obscure-brain-region-linked-feeding-frenzy-mice

B. Brookshire. The need to feed and eating for pleasure are inextricably linked. Science News Online, August 27, 2015. https://www.sciencenews.org/blog/scicurious/need-feed-and-eating-pleasure-are-inextricably-linked

https://www.sciencenews.org/article/how-obesity-makes-it-harder-taste

16margd
Apr 3, 2018, 8:02am Top

Good news: pasta linked to weight loss, when served in 1/2 c servings 3X daily. Apparently due to its low glycemic index.
(In attempt to maximize insoluble fiber in diet, I've been exploring pasta made from legumes. Most recently, DH used a chickpea tortellini--Banza brand--to make a pasta salad for a road trip. Yum! Though Banza isn't particularly cheap...)

Laura Chiavaroli et al. 2018. Effect of pasta in the context of low-glycaemic index dietary patterns on body weight and markers of adiposity: a systematic review and meta-analysis of randomised controlled trials in adults. BMJ Volume 8, Issue 3. http://bmjopen.bmj.com/content/8/3/e019438

Conclusions Pasta in the context of low-GI dietary patterns does not adversely affect adiposity and even reduces body weight and BMI compared with higher-GI dietary patterns. Future trials should assess the effect of pasta in the context of other ‘healthy’ dietary patterns.
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Eating Pasta Linked to Weight Loss in New Study
Kashmira Gander | 4/3/18
http://www.newsweek.com/pasta-weight-loss-869178

...The study emphasized that the inclusion of whole grains does not significantly affect pasta's GI status. And while it is relatively low in fiber, pasta has a similar GI rating to fiber-rich foods such as barley, legumes and steel cut oats, and a lower rating than wholewheat bread, breakfast cereals like bran flakes and potatoes with skin. On average, white pasta also has a higher micronutrient content than other white wheat products...

172wonderY
Apr 30, 2018, 11:05am Top

The new film 'I Feel Pretty' addresses female body image.

Film review:
Review: ‘I Feel Pretty’ Doesn’t Even Go Skin Deep

"The idea that a lack of self-confidence can be essentially bootstrapped away — that all we need to combat oppressive forces is the power of positive thinking and a flattering lipstick — is an exhausted, false fairy tale, one peddled by (among others!) self-help books, beauty companies and, disappointingly, movies like this one."

Commentary:
‘I Feel Pretty’ and the Rise of Beauty-Standard Denialism

"The movie suggests that the only thing holding back regular-looking women is their belief that looking regular holds them back at all. That attitude puts the onus on individual women to improve their self-esteem instead of criticizing societal beauty standards writ large. The reality is that expectations for female appearances have never been higher. It’s just become taboo to admit that."

Reader opinions:
A Woman’s Beauty: Who Gets to Decide?

18margd
Jun 11, 2018, 10:26am Top

Best results for reducing volume of food consumed: use 10" plates and turn tv off for dinner. Eight other behavioral changes rated for compliance and weight loss in Table 1. Looks like some might be more effective if employed more frequently.

Brian Wansink, David R. Just, and Collin R. Payne. 2009. Mindless Eating and Healthy Heuristics for the Irrational. American Economic Review: Papers & Proceedings 2009, 99:2, 165–169. http://www.aeaweb.org/articles.php?doi . http://www.indiana.edu/~abcwest/pmwiki/CAFE/wansink,just,payne.mindless.eating.h...

19margd
Jun 14, 2018, 8:56pm Top

Cell Metabolism, DiFeliceantonio and Coppin et al.: "Supra-Additive Effects of Combining Fat and Carbohydrate on Food Reward" https://www.cell.com/cell-metabolism/fulltext/S1550-4131(18)30325-5 , DOI: 10.1016/j.cmet.2018.05.018 . https://www.sciencedirect.com/science/article/pii/S1550413118303255

Highlights

• Fat and carbohydrate interact to potentiate reward independently of liking
• This is reflected in supra-additive responses in the striatum during food valuation
• Participants are able to estimate energy density from fat, but not carbohydrate
• Accurate estimation of energy density recruits a prefrontal-fusiform gyrus circuit
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Foods combining fats and carbohydrates more rewarding than foods with just fats or carbs
Cell Press | June 14, 2018

...Researchers show that the reward center of the brain values foods high in both fat and carbohydrates—i.e., many processed foods—more than foods containing only fat or only carbs. A study of 206 adults, to appear June 14 in the journal Cell Metabolism, supports the idea that these kinds of foods hijack our body's inborn signals governing food consumption.

...After the domestication of plants and animals and the development of grain and dairy production around 12,000 years ago, opportunities to consume fat and carbohydrates together increased, but processed foods like donuts, which could contain 11 grams of fat and 17 grams of carbohydrate, have only been around for 150 years, not long enough for us to evolve a new brain response to them.

Scientists believe our past experience with the nutritive properties of carbohydrates releases dopamine in the brain through an as-yet-unknown metabolic signal. These kinds of signals seem to help regulate what and how much we eat.

The researchers theorize that the simultaneous activation of fat and carbohydrate signaling pathways launches an effect that human physiology has not evolved to handle. Consistent with this suggestion, rodents given access to fat alone or carbohydrate alone regulate their total daily caloric intake and body weight. But given unrestricted access to fat and carbohydrates, they quickly gain weight.

https://medicalxpress.com/news/2018-06-foods-combining-fats-carbohydrates-rewarding.html

20pmackey
Jun 27, 2018, 10:04am Top

>18 margd: Thanks for this post, margd. This is actually helpful. I'm prediabetic and struggle to improve my eating habits. The suggestions in the article will help. According to this, I need to stop eating Monday night dinner while watching my Westworld recording. :(

21margd
Jun 27, 2018, 12:35pm Top

>20 pmackey: Soluble fiber might help stave off diabetes--oatmeal, legumes, reheated potatoes, etc. Maybe try powdered soluble fiber in your morning coffee (like a creamer only tasteless) to help you approach the 37 grams found effective below. (Increase GRADUALLY to this level.) Inulin powder mentioned below is widely available in pharmacies--store brands even. Maybe other soluble fiber powders as well. Heather's Tummy Fiber (gum of Acacia senegal) is available online.

Might be worth buying a glucose monitor: easier to stay with new eating habits if improvements show up every morning before breakfast!

Enlisting Gut Bacteria And Fiber To Fight Diabetes
Brenda Goodman | March 9, 2018

...Could High-Fiber Diets Stave Off Diabetes?

...27 people with type 2 diabetes on a very high-fiber diet ... followed...for 12 weeks, measuring changes to their blood sugar, and also to their gut bacteria.

They compared this group with 16 others who also had type 2 diabetes who got standard advice on exercise and eating right for diabetes along with a diet for the study that racked up roughly same number of calories, but had a lot less fiber.

The high-fiber group was getting a whopping 37 grams of fiber a day, while the group getting the average, healthy diet was eating about 16 grams of fiber a day -- which, by chance, is about what American adults average.

Both groups were also taking a medication called acarbose to help manage their blood sugar. Acarbose acts a bit like fiber in that it prevents some carbohydrates from being digested in the gut for energy. Before the study, all participants were weaned off any other medications to manage their blood sugar. If they used insulin, it was adjusted as needed throughout the study.

Both groups improved, but by the end of the experiment, the group on the very high-fiber diet was healthier than the group getting standard care. They had better control of their blood sugar, and they’d lost a bit more weight. About 90% of the high-fiber group achieved good control of their blood sugar -- keeping their hemoglobin A1c under 7%, the target recommended by the American Diabetes Association -- compared with just 50% of the group on a standard diabetes diet.

Here’s why that could be true.

All that fiber, which came from a wide variety of food sources, fertilized the growth of 15 strains of bacteria that produce certain short-chain fatty acids. Those acids act as both a fuel source for cells and as messengers.

In the new study, these short-chain fatty acids signaled the gut to make more glucagon-like peptide-1 (GLP-1) and peptide YY (PYY).

GLP-1 is a hormone that tells the body to make more insulin, while PYY dials down appetite. The two are critical in keeping blood sugar and weight under control.

Some diabetes drugs also work by increasing GLP-1. The increase in short-chain fatty acids also made the gut walls unfriendly to other kinds of bacteria that block GLP-1, boosting the effect.

“This is one benefit, one reason why high-fiber diets work,” says study researcher Liping Zhao, PhD, a professor of applied microbiology at both Rutgers University in New Brunswick, NJ, and Shanghai Jiao Tong University in Shanghai, China.

To make sure it was the change in gut bacteria that was driving the results -- and not something else -- the scientists then transferred the gut bacteria from their study participants to mice that were bred to be germ-free. Because they were bred not to have any of their own gut bacteria, scientists could later introduce bacteria and watch what happened as they started growing.

The mice that got the bacteria from the humans on the high-fiber diets had better fasting blood sugar levels than mice that got bacteria from people on the usual diabetes diet, even though they were eating the same chow.

The study was published in the journal Science.

Getting More Daily Fiber

The study authors say it would be difficult for the average person to copy their high-fiber diet. People in the high-fiber part of the study ate a specially prepared gruel made from oats, white beans, yellow corn, red beans, yams, peanuts, and lotus seeds, along with two whole grains that are unfamiliar to Westerners -- green buckwheat and adlay, or Job’s tears. They also got more fiber in the form of powders that included bitter melon, kudzu starch, inulin, and resistant dextrin...

https://www.webmd.com/diabetes/news/20180309/enlisting-gut-bacteria-and-fiber-to-fight-diabetes
__________________________________________________​

Rutgers University. "Fiber-fermenting bacteria improve health of type 2 diabetes patients: Dietary fibers promote gut bacteria that benefit blood glucose control." ScienceDaily. ScienceDaily, 8 March 2018.
__________________________________________________​

Liping Zhao, Feng Zhang, Xiaoying Ding, Guojun Wu, Yan Y. Lam, Xuejiao Wang, Huaqing Fu, Xinhe Xue, Chunhua Lu, Jilin Ma, Lihua Yu, Chengmei Xu, Zhongying Ren, Ying Xu, Songmei Xu, Hongli Shen, Xiuli Zhu, Yu Shi, Qingyun Shen, Weiping Dong, Rui Liu, Yunxia Ling, Yue Zeng, Xingpeng Wang, Qianpeng Zhang, Jing Wang, Linghua Wang, Yanqiu Wu, Benhua Zeng, Hong Wei, Menghui Zhang, Yongde Peng, Chenhong Zhang. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science, 2018; 359 (6380): 1151 DOI: 10.1126/science.aao5774
http://science.sciencemag.org/content/359/6380/1151

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22pmackey
Jun 27, 2018, 12:54pm Top

>21 margd: Thanks, I really appreciate your taking the time to write all this. Funny you mention fiber. You're the second person this year. A friend of mine is a retired Home Economics (I don't know the right term anymore) teacher who told me the same thing: Focus on fiber. I've been focused on counting carbs (increasing good carbs, cutting out bad). A month ago, my doctor put me on Trulicity which slows down digestion. That has helped smooth out the sugar highs and lows -- the carb cravings were hard to deal with.

23margd
Jul 10, 2018, 8:05am Top

We evolved during periods of starvation. No surprise that body has so many ways to have us eat, even in plenty. Here's yet another one:

S.X. Luo et al. Regulation of feeding by somatostatin neurons in the tuberal nucleus. Science. Vol. 361, July 6, 2018, p. 76. doi:10.1126/science.aar4983. http://science.sciencemag.org/content/361/6397/76

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Nerve cells that help control hunger have been ID’d in mice
Targeting similar cells in people could mark a new way to regulate appetites
Laura Sanders | July 5, 2018

Newly identified nerve cells deep in the brains of mice compel them to eat. Similar cells exist in people, too, and may ultimately represent a new way to target eating disorders and obesity.

...Certain nerve cells in the human brain region called the nucleus tuberalis lateralis, or NTL, are known to malfunction in neurodegenerative diseases such as Huntington’s and Alzheimer’s.

...In people, the NTL is a small bump along the bottom edge of the hypothalamus, a brain structure known to regulate eating behavior. But in mice, a similar structure wasn’t thought to exist at all, until Fu and colleagues discovered it by chance.

...The neurons sprang into action when the mice were hungry, or when the hunger-signaling hormone ghrelin was around, the team found. And when the researchers artificially activated the cells, using either laser light or molecular techniques, the mice ate more and gained weight faster than normal mice. Conversely, when the researchers killed the neurons, the mice didn’t eat as much and gained less weight than mice that still possessed the cells. The results suggest that, in mice, these neurons influence the impulse to eat — and subsequent changes in weight.

...Both Alzheimer’s and Huntington’s have been tied to metabolic problems and changes in appetite. The demise of appetite-controlling cells in the NTL might help explain why.

If NTL cells do control appetite in humans, that brain region wouldn’t be working alone. Far from it. Neighboring nerve cells in and around the hypothalamus are also known to play big roles in prodding the body to eat when food is available

...Tweaking the behavior of these appetite-controlling cells, perhaps with drugs, may one day offer a way to treat obesity or eating disorders such as anorexia.

https://www.sciencenews.org/article/nerve-cells-help-control-hunger-have-been-identified-mice

24margd
Sep 12, 2018, 4:01am Top

Early gene mutation, which may have led to rise of genus Homo, is a mixed blessing--increases risk of Type 2 diabetes.

A single gene mutation may have helped humans become optimal long-distance runners
September 11, 2018, University of California - San Diego

...lost gene may also have contributed to humanity's well-documented claim to be among the best long-distance runners in the animal kingdom.

...might have contributed to the origin of Homo, the genus that includes modern Homo sapiens and extinct species like Homo habilis and Homo erectus.

...contributed to improved skeletal muscle capacity for oxygen utilization...

...enhanced innate immunity in early hominids...

...certain sialic acids are associated with increased risk of type 2 diabetes; may contribute to elevated cancer risk associated with red meat consumption; and trigger inflammation.

"They are a double-edged sword," said Varki. "The consequence of a single lost gene and a small molecular change that appears to have profoundly altered human biology and abilities going back to our origins."...

https://phys.org/news/2018-09-gene-mutation-humans-optimal-long-distance.html

More information: Human-like Cmah Inactivation in Mice Increases Running Endurance and Decreases Muscle Fatigability: Implications for Human Evolution, Proceedings of the Royal Society B, rspb.royalsocietypublishing.or … .1098/rspb.2018.1656
__________________________________________________​

Missing molecule raises diabetes risk in humans
March 2, 2011, University of California - San Diego
https://medicalxpress.com/news/2011-03-molecule-diabetes-humans.html

25margd
Sep 17, 2018, 9:12am Top

I didn't see mechanism by which household disinfectants might be affecting children's gut biota and weight, e.g.,
1. did disinfectant reduce microbes available TO baby,
2. kill some species microbes IN baby,
3. eco-friendly products are just marker for healthier diet & habits in the home, or
4. ____?
I suspect # 1 and 3?
__________________________________________________​

Household disinfectants could be making kids overweight by altering their gut microbiota (1:00)
CMAJ | Sep 17, 2018

Research published in the Canadian Medical Association Journal has found that household cleaning products may contribute to kids' overweight by altering their gut microbiota.

https://www.youtube.com/watch?v=2OUXHwkpc28
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Household cleaning products may contribute to kids' overweight by altering their gut microbiota
September 17, 2018, Canadian Medical Association Journal

...analyzed the gut flora of 757 infants from the general population at age 3-4 months and weight at ages 1 and 3 years, looking at exposure to disinfectants, detergents and eco-friendly products used in the home.

...Associations with altered gut flora in babies 3-4 months old were strongest for frequent use of household disinfectants such as multisurface cleaners, which showed lower levels of Haemophilus and Clostridium bacteria but higher levels of Lachnospiraceae. The researchers also observed an increase in Lachnospiraceae bacteria with more frequent cleaning with disinfectants. They did not find the same association with detergents or eco-friendly cleaners. Studies of piglets have found similar changes in the gut microbiome when exposed to aerosol disinfectants.

"...when they were 3 years old, their body mass index was higher than children not exposed to heavy home use of disinfectants as an infant"...

Babies living in households that used eco-friendly cleaners had different microbiota and were less likely to be overweight as toddlers.

"Those infants growing up in households with heavy use of eco cleaners had much lower levels of the gut microbes Enterobacteriaceae. However, we found no evidence that these gut microbiome changes caused the reduced obesity risk," she said.

She suggests that the use of eco-friendly products may be linked to healthier overall maternal lifestyles and eating habits, contributing in turn to the healthier gut microbiomes and weight of their infants...

https://medicalxpress.com/news/2018-09-household-products-contribute-kids-overweight.html

__________________________________________________​

Mon H. Tun et al. Postnatal exposure to household disinfectants, infant gut microbiota and subsequent risk of overweight in children, Canadian Medical Association Journal (2018). DOI: 10.1503/cmaj.170809

Conclusion

Antibacterial cleaning products have the capacity to change the environmental microbiome and alter risk for child overweight. Our study provides novel information regarding the impact of these products on infant gut microbial composition and outcomes of overweight in the same population. We found Lachnospiraceae to be enriched in infant gut microbiota with frequent postnatal use of domestic disinfectants but not eco-friendly products; genus Clostridium and Haemophilus were reduced concurrently. Evidence of statistical mediation with Lachnospiraceae abundance showed a role for this disinfectant-related change to gut microbiota in causing overweight. We did not observe mediation for infant fecal Enterobacteriaceae, suggesting an alternate pathway for the association between postnatal eco-friendly product use and reduced child overweight. Further study is required on the mechanisms through which household cleaning products alter gut microbial composition and the subsequent role this might have on metabolic disease...

Questionnaire: http://www.cmaj.ca/content/cmaj/suppl/2018/09/13/190.37.E1097.DC1/170809-res-1-a...
Use frequency: daily weekly monthly less than monthly not used

Disinfectants
1 Multisurface cleaner
2 Toilet Bowl Cleaner
3 Purell type cleaner
4 Floor cleaner
5 Bleach
6 Disinfectant in home in general
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The association between ownership of common household devices and obesity and diabetes in high, middle and low income countries
Scott A. Lear, CMAJ

Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months
Meghan B. Azad, CMAJ

Effects of low income on infant health
Louise Séguin, CMAJ

How delivery mode and feeding can shape the bacterial community in the infant gut
Se Jin Song, CMAJ

Prevalence of and risk factors for childhood overweight and obesity
Paul J. Veugelers et al., CMAJ

Household cleaning products may contribute to kids' overweight by altering their gut microbiota
MedicalXpress

Roles of Birth Mode and Infant Gut Microbiota in Intergenerational Transmission of Overweight and Obesity From Mother to Offspring
Hein M. Tun et al., JAMA Pediatr

Gut Microbiota May Affect Vertical Transmission of Being Overweight
PracticeUpdate

Association of Exposure to Formula in the Hospital and Subsequent Infant Feeding Practices With Gut Microbiota and Risk of Overweight in the First Year of Life
Malcolm R. Sears et al., JAMA Pediatr

Association of Obesity With Feeding Practices in Infancy
PracticeUpdate

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Moira K. Differding et al. Are household disinfectants microbially mediated obesogens?, Canadian Medical Association Journal (2018). DOI: 10.1503/cmaj.181134

26margd
Sep 27, 2018, 6:40am Top

Activity by the choline-cutting microbes could play a role in obesity and may diminish availability of the nutrient to mom and fetus during pregnancy:

K.A. Romano et al. Metabolic, epigenetic, and transgenerational effects of gut bacterial choline consumption. Cell Host & Microbe. Vol. 22, September 13, 2017, p. 279. doi:10.1016/j.chom.2017.07.021. https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30304-9
Highlights

Gut bacteria compete with the host for choline, decreasing bioavailability
Microbial choline degradation depletes methyl-donor metabolites
Microbial choline utilization alters in utero epigenetic programming of the brain
Mice with choline-consuming gut microbiota display altered behavior

Summary
Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assessed the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community that lacks a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites and recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria showed increased susceptibility to metabolic disease in the context of a high-fat diet. Furthermore, bacterially induced reduction of methyl-donor availability influenced global DNA methylation patterns in both adult mice and their offspring and engendered behavioral alterations. Our results reveal an underappreciated effect of bacterial choline metabolism on host metabolism, epigenetics, and behavior. This work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal nutrient intake requirements.

27margd
Nov 12, 2018, 10:08am Top

How Dad’s Stresses Get Passed Along to Offspring
Esther Landhuis on November 8, 2018

Mouse studies show tiny intercellular pods convey to sperm a legacy of a father’s hard knocks in life

A stressed-out and traumatized father can leave scars in his children. New research suggests this happens because sperm “learn” paternal experiences via a mysterious mode of intercellular communication in which small blebs break off one cell and fuse with another.

Carrying proteins, lipids and nucleic acids, these particles ejected from a cell act like a postal system that extends to all parts of the body, releasing little packages known as extracellular vesicles. Their contents seem carefully chosen. “The cargo inside the vesicle determines not just where it came from but where it’s going and what it’s doing when it gets there,” says Tracy Bale, a neurobiologist at the University of Maryland School of Medicine.

Preliminary research Bale and others, announced this week at the annual meeting of the Society for Neuroscience in San Diego, shows how extracellular vesicles can regulate brain circuits and help diagnose neurodegenerative diseases—in addition to altering sperm to disrupt the brain health of resulting offspring.

Striking evidence that harsh conditions affect a man’s children came from crop failures and war ravaging Europe more than a century ago. In those unplanned human experiments, prolonged famine appeared to set off a host of health changes in future generations, including higher cholesterol levels and increased rates of obesity and diabetes....

https://www.scientificamerican.com/article/how-dads-stresses-get-passed-along-to-offspring/

28margd
Nov 15, 2018, 9:03am Top

"OUR OBSERVATIONS CHALLENGE THE BELIEF THAT ALL CALORIES ARE THE SAME TO THE BODY"

__________________________________________________​

Cara B Ebbeling et al. 2018. Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial
BMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k4583 (Published 14 November 2018)

Abstract
Interventions. After 12% weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%; moderate, 40%; or low, 20%) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose).

Results. Total energy expenditure differed by diet in the intention-to-treat analysis, with a linear trend of 52 kcal/d for every 10% decrease in the contribution of carbohydrate to total energy intake. Change in total energy expenditure was 91 kcal/d greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis, the respective differences were 131 kcal/d and 278 kcal/d. Among participants in the highest third of pre-weight loss insulin secretion, the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis). Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet (both analyses). Leptin was also significantly lower in participants assigned to the low carbohydrate diet (per protocol).

Conclusions Consistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion.

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Low-carb diets cause people to burn more calories
Children's Hospital Boston | November 14, 2018,

Most people regain the weight they lose from dieting within one or two years, in part because the body adapts by slowing metabolism and burning fewer calories. A meticulous study led by Boston Children's Hospital, in partnership with Framingham State University, now finds that eating fewer carbohydrates increases the number of calories burned. The findings, published November 14 in the BMJ, suggest that low-carb diets can help people maintain weight loss, making obesity treatment more effective.

...Over the 20 weeks, total energy expenditure was significantly greater on the low-carbohydrate diet versus the high-carbohydrate diet. At the same average body weight, participants who consumed the low-carb diet burned about 250 kilocalories a day more than those on the high-carb diet.

"If this difference persists—and we saw no drop-off during the 20 weeks of our study—the effect would translate into about a 20-pound weight loss after three years, with no change in calorie intake," says Ebbeling.

In people with the highest insulin secretion at baseline, the difference in calorie expenditure between the low- and high-carb diets was even greater, about 400 kilocalories per day, consistent with what the Carbohydrate-Insulin Model would predict. Ghrelin, a hormone thought to reduce calorie burning, was significantly lower on the low- versus high-carb diet.

"Our observations challenge the belief that all calories are the same to the body," says Ebbeling. "Our study did not measure hunger and satiety, but other studies suggest that low-carb diets also decrease hunger, which could help with weight loss in the long term."...

https://medicalxpress.com/news/2018-11-low-carb-diets-people-calories.html

29margd
Dec 7, 2018, 12:00pm Top

...Snack on Brazil Nuts

We’ve known noshing on nuts instead of empty calories is healthy, but now researchers have zeroed in on what may be the best nut for keeping off extra pounds — Brazil nuts. Their slimming secret comes from their especially high content of the mineral selenium, which is used to make a hormone that regulates body weight; low levels of the mineral have been reported in obese people, says Mee Young Hong, a professor in the School of Exercise and Nutritional Sciences at San Diego State University. While the average nut has anywhere from 3 to 5 micrograms of selenium per ounce, Brazil nuts have a whopping 544 micrograms.

Hong’s study, released today, compared the impact pretzels versus Brazil nuts had on blood sugar in a small group of healthy adults. He found that while pretzels caused blood sugar to spike, Brazil nuts helped to stabilize levels. Moreover, after eating Brazil nuts, people reported feeling fuller longer. In general, nuts are a good source of protein, fiber and healthy fats — and “all of these nutrients take longer to process and absorb, so the sensation of satiety lasts for a longer period,” Hong explains.

Brazil nuts aren’t your favorite? A tandem study, also released today, shows that eating 1 ounce daily of any nut — even peanuts — can help you stave off the one pound most adults gain each year. That’s what researchers at Harvard’s School of Public Health found in a study that analyzed data from records of more than 125,000 adults. Having nuts in your diet, researchers found, also helped people keep the weight off over a four-year period. Nuts were particularly helpful when eaten in place of red meat, french fries, chips or desserts, says Xiaoran Liu, lead author of the study and a research associate in the nutrition department of Harvard School of Public Health in Boston...

https://www.aarp.org/health/healthy-living/info-2018/heart-healthy-eating-aha.html

Also:

American Heart Association. "Nuts for nuts? Daily serving may help control weight and benefit health."
ScienceDaily, 5 November 2018.
www.sciencedaily.com/releases/2018/11/181105081742.htm

302wonderY
Dec 13, 2018, 9:13am Top

>29 margd: Aha! Christmas gifting idea help.

31margd
Dec 13, 2018, 9:51am Top

Brazil nuts almost sound too good to be true:

One study, at least, found that a single serving of Brazil nuts may bring cholesterol levels down faster than statin drugs and keep them down even a month after that single ingestion. (I used to keep a stash in the freezer, and grab one when I visited. Should restock.)

They grow best in pristine forests, so a resource for local people.

__________________________________________________​

Four Nuts Once a Month
Michael Greger M.D. FACLM September 15th, 2014 Volume 20

A single serving of Brazil nuts may bring cholesterol levels down faster than statin drugs and keep them down even a month after that single ingestion.

https://nutritionfacts.org/video/four-nuts-once-a-month/

__________________________________________________​

The Brazil nut family is in the order Ericales, as are other well-known plants such as blueberries, cranberries, sapote, gutta-percha, tea, phlox and persimmons.

The Brazil nut tree is...native to the Guianas, Venezuela, Brazil, eastern Colombia, eastern Peru, and eastern Bolivia. It occurs as scattered trees in large forests on the banks of the Amazon River, Rio Negro, Tapajós, and the Orinoco.

...The Brazil nut is a large tree, reaching 50 m (160 ft) tall and with a trunk 1 to 2 m (3.3 to 6.6 ft) in diameter, making it among the largest of trees in the Amazon rainforests. It may live for 500 years or more, and according to some authorities often reaches an age of 1,000 years.

...Brazil nut trees produce fruit almost exclusively in pristine forests, as disturbed forests lack the large-bodied bees of the genera Bombus, Centris, Epicharis, Eulaema, and Xylocopa which are the only ones capable of pollinating the tree's flowers, with different bee genera being the primary pollinators in different areas, and different times of year. Brazil nuts have been harvested from plantations, but production is low and is currently not economically viable.

...Brazil nuts for international trade can come from wild collection rather than from plantations. This has been advanced as a model for generating income from a tropical forest without destroying it. The nuts are gathered by migrant workers known as castanheiros.

Analysis of tree ages in areas that are harvested show that moderate and intense gathering takes so many seeds that not enough are left to replace older trees as they die. Sites with light gathering activities had many young trees, while sites with intense gathering practices had hardly any young trees.

https://en.wikipedia.org/wiki/Brazil_nut

32mamzel
Dec 13, 2018, 10:50am Top

> Funny, I used to think that Brazil nuts were just fillers in the can of mixed nuts. I thought they were quite greasy. I'll have to rethink that now.

33margd
Jan 11, 8:34am Top

An essay on one man's journey: he's Chris-Christie-sized, I think, and it hasn't been easy.

The Weight I Carry
Tommy Tomlinson | Jan 9, 2019

What it’s like to be too big in America

https://www.theatlantic.com/health/archive/2019/01/weight-loss-essay-tomlinson/579832/

34margd
Jan 11, 8:45am Top

Study* reveals how much fiber we should eat to prevent disease
Ana Sandoiu | jan 11, 2019

...Overall, the research found that people who consume the most fiber in their diet are 15–30 percent less likely to die prematurely from any cause or a cardiovascular condition, compared with those who eat the least fiber.

Consuming foods rich in fiber correlated with a 16–24 percent lower incidence of coronary heart disease, stroke, type 2 diabetes, and colon cancer.

Fiber-rich foods include whole grains, vegetables, fruit, and pulses, such as peas, beans, lentils, and chickpeas.

The analysis also revealed that the amount of fiber that people should consume daily to gain these health benefits is 25–29 grams (g). By comparison, adults in the United States consume 15 g of fiber daily, on average.

The authors also suggest that consuming more than 29 g of fiber per day may yield even more health benefits.

However, they do caution that, while the study in itself did not find any adverse health effects of consuming fiber, eating too much of it may be damaging for people with insufficient iron or minerals.

Eating large amounts of whole grains can further deplete the body of iron, explain the researchers.

Finally, the clinical trials included in the study also revealed that consuming more fiber correlates strongly with lower weight and lower cholesterol levels...

https://www.medicalnewstoday.com/articles/324153.php

__________________________________________________​

*Andrew Reynolds et al. 2019. Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. The Lancet.
January 10, 2019 DOI:https://doi.org/10.1016/S0140-6736(18)31809-9 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31809-9/fulltext

Summary

Background
Previous systematic reviews and meta-analyses explaining the relationship between carbohydrate quality and health have usually examined a single marker and a limited number of clinical outcomes. We aimed to more precisely quantify the predictive potential of several markers, to determine which markers are most useful, and to establish an evidence base for quantitative recommendations for intakes of dietary fibre.

Methods
We did a series of systematic reviews and meta-analyses of prospective studies published from database inception to April 30, 2017, and randomised controlled trials published from database inception to Feb 28, 2018, which reported on indicators of carbohydrate quality and non-communicable disease incidence, mortality, and risk factors. Studies were identified by searches in PubMed, Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, and by hand searching of previous publications. We excluded prospective studies and trials reporting on participants with a chronic disease, and weight loss trials or trials involving supplements. Searches, data extraction, and bias assessment were duplicated independently. Robustness of pooled estimates from random-effects models was considered with sensitivity analyses, meta-regression, dose-response testing, and subgroup analyses. The GRADE approach was used to assess quality of evidence.

Findings
Just under 135 million person-years of data from 185 prospective studies and 58 clinical trials with 4635 adult participants were included in the analyses. Observational data suggest a 15–30% decrease in all-cause and cardiovascular related mortality, and incidence of coronary heart disease, stroke incidence and mortality, type 2 diabetes, and colorectal cancer when comparing the highest dietary fibre consumers with the lowest consumers Clinical trials show significantly lower bodyweight, systolic blood pressure, and total cholesterol when comparing higher with lower intakes of dietary fibre. Risk reduction associated with a range of critical outcomes was greatest when daily intake of dietary fibre was between 25 g and 29 g. Dose-response curves suggested that higher intakes of dietary fibre could confer even greater benefit to protect against cardiovascular diseases, type 2 diabetes, and colorectal and breast cancer. Similar findings for whole grain intake were observed. Smaller or no risk reductions were found with the observational data when comparing the effects of diets characterised by low rather than higher glycaemic index or load. The certainty of evidence for relationships between carbohydrate quality and critical outcomes was graded as moderate for dietary fibre, low to moderate for whole grains, and low to very low for dietary glycaemic index and glycaemic load. Data relating to other dietary exposures are scarce.

Interpretation
Findings from prospective studies and clinical trials associated with relatively high intakes of dietary fibre and whole grains were complementary, and striking dose-response evidence indicates that the relationships to several non-communicable diseases could be causal. Implementation of recommendations to increase dietary fibre intake and to replace refined grains with whole grains is expected to benefit human health. A major strength of the study was the ability to examine key indicators of carbohydrate quality in relation to a range of non-communicable disease outcomes from cohort studies and randomised trials in a single study. Our findings are limited to risk reduction in the population at large rather than those with chronic disease.

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