Gut bacteria found to reverse autism-related social behavior

The mouse study joins a growing set of research that links the gut microbiome to the brain.

16th June 2016 in Life Sciences



Published today in Cell, the study found that the addition of the bacteria Lactobacillus reuteri, which is commonly found in human breast milk, increased the likelihood that previously antisocial mice would interact with each other. Lead author Shelly Buffington told us how the study could translate to the treatment of Autism Spectrum Disorder (ASD) and other neurodevelopmental disorders in humans.

ResearchGate: Can you explain your study and the significance of your findings?

Shelly Buffington: We found that a maternal high-fat diet in mice alters offspring social behavior and induces long-term changes in the offspring gut microbiome. We performed a series of co-housing experiments and fecal microbiota transplants into germ-free mice to determine if the alterations in the high-fat diet offspring microbiome were causative factors underlying their impaired social behavior. Our results suggested that there were one or more bacterial species in the regular mouse gut that are important for normal social behavior that were missing or underrepresented in the maternal high-fat diet gut microbiome. We used whole genome shotgun sequencing to analyze the composition of the regular vs. maternal high-fat diet offspring gut microbiome. These data revealed a marked shift in microbial ecology at the species level.

The most underrepresented species in the maternal high-fat diet gut microbiome was Lactobacillus reuteri. This finding was very intriguing because Lactobacillus reuteri had previously been shown to increase the levels of the hormone oxytocin, which has been dubbed “the social hormone” as there is a lot of evidence that it plays an important role in modulating social behaviors in mammals. We then tested whether the introduction of Lactobacillus reuteri into the gut of maternal high-fat diet offspring was enough to reverse their social deficits. When we next assessed their social behavior, we found that it was restored. We found that treatment with Lactobacillus reuteri significantly increased the number of oxytocin-producing cells in the brains of maternal high-fat diet offspring and restored, what we believe to be, social interaction-related plasticity in a key reward area of the brain.

Our results suggest that maternal diet-induced changes in the gut the microbiome can affect offspring social behavior and that single species reconstitution of Lactobacillus reuteri can rescue these deficits. Furthermore, they add to a growing literature showing that the gut microbiome is an important player when it comes to behavior and that probiotics may hold therapeutic potential for the treatment of behavioral symptoms associated with neurodevelopmental disorders.

RG: Can you explain the method you used to reach these findings?

Buffington: We used a powerful combination of techniques including behavioral tests, 16S ribosomal RNA gene sequencing, whole genome shotgun sequencing, immunofluorescence microscopy, electrophysiology, and pharmacological approaches to study the link between maternal diet-induced changes in the offspring gut microbiome and behavior. Our study is one of the first to combine a species-level analysis of the composition of the gut microbiome not only with behavioral assessment but also with functional analysis of plasticity in the brain.

ResearchGate: Do you know why the gut microbiome has such an impact on the brain?

Buffington: Communication between gut microbiota and the brain is complex –we don't fully understand it yet, but we do know it's bidirectional and multifaceted. No system works in isolation, there's a significant amount of molecular cross-talk. One of the primary mediators between the gut and the brain is the vagus nerve, which provides two-way communication. Many, but not all, probiotics that alter the brain and behavior in animal models depend on the integrity of the vagus nerve.

Another way gut microbiota can affect brain function is through stimulation of the immune system, altering the levels of both pro- and anti-inflammatory cytokines in the bloodstream. Dietary changes, for example, can compromise intestinal barrier integrity creating a route for bacterial products to enter the circulation and induce inflammation. Gut bacteria also generate metabolic byproducts, including short-chain fatty acids, which have been shown to modulate brain function and behavior, as they breakdown dietary constituents. Certain species of gut bacteria even produce neurotransmitters including GABA, serotonin, dopamine, and acetylcholine as well as neurotransmitter precursors. Elucidating the mechanisms by which the gut modulates brain activity and vice versa is an exciting, active area of investigation that holds great promise for identifying novel therapeutic targets.

RG: What spurred you to look into the connection between the gut and the brain in the treatment of Autism-related antisocial behaviors?

Buffington: There has been a lot of great work published recently showing that bidirectional communication exists between the gut and the brain. This communication pathway is colloquially termed the “gut-brain axis.” Human epidemiological studies have shown that maternal obesity increases the risk of neurodevelopmental disorders in offspring. The same has been found in non-human primates.

In addition, many ASD patients co-present with gastrointestinal disorders, suggesting that they may have an imbalance in gut microbiota which contributes to their intestinal issues. When we observed abnormal social behavior in our maternal high-fat diet mice, we hypothesized that changes in the maternal microbiome could in turn alter the offspring gut microbiome and that these alterations could underlie their behavioral deficits.

RG: What kind of behavioral improvements did you find in the mice who had a full restoration of their gut microbiome?

Buffington: We found that the maternal high-fat diet offspring that had been co-housed with mice with a normal microbiome preferred to interact with a mouse over an inanimate object. They also spent more time in contact with a stranger mouse when they were placed together in a neutral arena. Thus, they displayed normal social behavior, for mice.

RG: Do you have any idea how this study could translate to human ASD sufferers?

Buffington: There is a lot of interest in the potential of probiotic treatments for alleviating behavioral symptoms in kids with ASD. The promise of our work lies in the finding that a single bacterial species, Lactobacillus reuteri, was able to reverse social behavioral deficits in maternal high-fat diet offspring. Not only did it restore the behavioral symptoms, but when we looked at the brains of the treated animals, we found that it also increased oxytocin levels. Several studies have suggested that oxytocin plays an important role in modulating social behavior, not only in rodents, but in humans. Our findings suggest that Lactobacillus reuteri could prove to be useful as a novel, low-risk probiotic for treatment of behavioral symptoms associated with ASD.

Image credit Wiki Media.

https://www.researchgate.net/blog/post/gut-bacteria-found-to-reverse-autism-related-social-behavior

Curious Cook: A time for gut feelings, part 1

It is sheepish to admit, especially as I am normally a demure, diffident person – but nobody has ever accused me of being over-restrained at feasts, especially if fine food, lots of alcohol and good company are present. Needless to say, there are consequences, and in my case it often results in a hazy sense of bodily unease (which lasts for days), combined with a rock-solid bout of constipation.

February 11, 2018 Food, Food News

By CHRIS CHAN

The wooziness from drinking inevitably subsides after a while, but the guts can feel the consequences of bingeing long after. Photo: VisualHunt

Therefore I would not suggest anyone emulate this propensity for overindulgence – especially as I am not unaware of what is happening to the body in these situations. For example, there is increased risk of liver cirrhosis – and several million brain neurons were probably fried by the alcohol.

Perhaps up to 4% of all deaths worldwide are related to alcohol abuse, though surprisingly only around 20% of heavy drinkers actually develop cirrhosis. By heavy drinking, one definition is consuming 100ml (80g) or more of ethanol a day for a period of 10 years or longer.

Many countries use “units of alcohol” (UA) to measure alcohol consumption – a UA is 10ml (8g) of ethanol so a pint of beer would be 2 UA or more (it depends on the strength of the beer). Therefore 100ml (80g) of ethanol is simply 10 UA – and in case you are curious, the reason why 100ml of alcohol is only 80g by weight is because ethanol is lighter than water.

A bottle of wine has around 9-10 UA so to run a 20% chance of developing cirrhosis, statistically one has to drink at least a bottle of wine a day for several years. However, statistics do not really help if there is a genetic disposition for cirrhosis.

This might apply to a significant proportion of humans who are genetically unable to produce enzymes called Aldehyde Dehydrogenases (ALDH1 and ALDH2) which are needed to neutralise acetaldehyde, a toxic compound created during the processing of alcohol in the body.

Prime examples are most Asians who lack the ability to express ALDH1 and ALDH2, so excessive alcohol consumption may be considerably more toxic for them. If you are interested, please read “A cure for hangover and – hic! – other holiday tales“.

Also, statistics indicate that consuming more than 26g of ethanol a day (just over 3 UA) increases the chances of bowel cancer by 21% – as Britain’s general incidence of bowel cancer is 6%, this increases the risk to about 7.25% overall.

Statistically, one has to drink at least a bottle of wine a day for several years to run a 20 chance of developing cirrhosis.

The Real Concern

Sobering as the facts about alcohol are, I have another more personal concern. The wooziness from drinking inevitably subsides after a while, but the disquiet is over the onset of intestinal issues after binging on food and alcohol – specifically the general feeling of corporeal unease and constipation which lasts for days.

The background for this worry is a little long-winded, so please bear with me.

My father eventually succumbed to complications after suffering for over 15 years from Parkinson’s Disease (PD). His PD was as severe as it was unexpected – nobody else in the family had the disease and it was immensely tragic watching him descend from an intelligent, outgoing human into someone who needed a handkerchief near the mouth at all times.

The severity of his condition meant that none of the usual PD drugs worked and he eventually contracted a severe infection in a hospital after treatment for respiratory issues. This finally killed him, and not in a pleasant way.

As such, PD is a subject which I keep an eye on – not least because as my father’s son, I have a statistically higher chance of developing this terrifying disease. There is some evidence that the disease may be hereditary (due to indeterminate research into various PARK genes) – but there is more evidence that PD can be caused by environmental factors.

Some characteristics of PD, apart from symptoms such as uncontrollable tremors and lack of motor control, are over-aggregations of proteins called alpha-synuclein (a-syn) in the nervous systems and the abundance of inflammatory compounds called cytokines in the brain – in combination, these compounds seemingly damage the brain neurons controlling motor functions.

Other lesser known symptoms of most PD patients are intestinal problems, mainly constipation.

The concern about intestinal well-being is based on sobering research which found links between PD and the human gastrointestinal microbiota (HGM), the colonies of bacteria present in all human intestines.

A 2016 paper from the University of Wisconsin-Madison discovered that patients with PD have a significantly different composition of gut bacteria from normal people – this supported a hypothesis published by the University of Frankfurt in 2003.

When gut material from PD patients were transplanted into the guts of germ-free mice without PD, the test mammals began to display symptoms of PD. Even more curious was an experiment at CalTech where mice specially engineered to overproduce a-syn in their brains did not develop PD symptoms until gut matter from PD patients was implanted into their guts – control faecal material from normal people had a much smaller impact on motor dysfunction on such mice.

Despite the dramatic inferences, I should add that none of this is conclusive proof as yet (there may be other indeterminate causes of PD) – but it is certainly plausible that some relationship exists between a defective HGM and PD.

Interestingly, the Wisconsin-Madison team also provided a possible explanation: the flawed HGM in PD patients may cause significant overproduction of certain short-chain fatty acids (SCFA) (such as acetate, butyrate, propionate, etc) which are known to activate immune responses in neurons.

This was based on experiments where (i) SCFAs were fed to mice; (ii) faecal material from PD patients were transplanted into mice; and (iii) gut matter from normal humans were transplanted into mice – only the first two groups of mice developed symptoms of PD.

The University of Luxembourg and University of Alabama have also detected similar connections between PD and HGM. The Luxembourg paper goes further and suggested a link between a problematic HGM and the sleeping condition called Idiopathic Rapid-Eye-Movement Sleep Behaviour Disorder (iRBD) – and people with iRBD have a higher risk of developing PD in later life.

They also identified a relationship between certain HGM bacteria and depression.

An earlier 2012 joint paper by Harvard Medical School and Oxford University proposed that dysbiosis (an impairment of the HGM) is the root cause of many illnesses, including Irritable Bowel Syndrome, metabolic diseases, allergies, cardiovascular issues and, once again, neurological diseases.

Experiments done on mice at CalTech in 2013 also suggested a link between autism and HGM bacteria called Bacteroides fragilis which are notably lacking in children with autism, though it was unclear whether the link was causal or consequential.

HGM And Bingeing

Amazingly, it is only within the last few years that science is starting to quantify how seriously important HGM is to overall health – previously it was mostly theories and anecdotal inferences.

You probably know that humans have a second brain called the Enteric Nervous System (ENS) which also significantly affects well-being – this was discovered less than 20 years ago, and the HGM is contained within the ENS. If you are interested, read this short story, “The nine-metre brain“.

Therefore, the concern is that a bad (or excessive) diet can cause some sort of damage to HGM – which in turn can cause problems affecting the health of the rest of the body, including the brain. It is a plausible explanation as to why I (and probably many other people) feel disquieted and constipated for days after serious bingeing on rich food and alcohol.

Note that the ENS is made up of neurons (like the brain) and any activity that can destroy ENS neurons can probably spread to the brain eventually.

As an aside, laxatives are often used to treat constipation, but overuse can cause side-effects and obscure underlying HGM issues. How various laxatives work depends on their chemicals (and it is complicated to explain everything) – but they can be extremely effective (eg. magnesium citrate) so I would not suggest taking laxatives with a sleeping pill.

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There will be more on how bad diets and over-indulgence affect the HGM in the next part.

https://www.star2.com/food/2018/02/11/curious-cook-gut-feelings-part-1/

Deadlier Than You've Been Told, Test Your Levels Before It's Too Late

While many continue to believe it's relatively benign, the latest studies are truly frightening - which is a serious concern when you consider lab tests have detected it in urine and breastmilk. Please don't ignore, test your personal levels today.

Poisoned Field: Glyphosate, the Underrated Risk?
December 24, 2016

Story at-a-glance

• The documentary “Poisoned Fields: Glyphosate, the Underrated Risk?” chronicles the risks of glyphosate to human health and the environment
• Researchers found severely restricted, damaged root growth among plants growing in fields treated with glyphosate for more than a decade
• Farmers also noted correlations between glyphosate in animal feed and rates of miscarriage, deformities in piglets and infertility among farm animals

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By Dr. Mercola

Glyphosate, the active ingredient in Monsanto's Roundup, is an herbicide like no other, as more tons of it have been sprayed worldwide than any other herbicide before it.

Writing in Environmental Sciences Europe, scientists noted that in the U.S. and likely globally, "no pesticide has come remotely close to such intensive and widespread use."1

"Glyphosate will likely remain the most widely applied pesticide worldwide for years to come," they continued earlier this year, which is alarming as its environmental and public health risks become increasingly apparent.

Glyphosate is used in large quantities on genetically engineered (GE) glyphosate-tolerant crops (i.e., Roundup Ready varieties). Its use actually increased nearly 15-fold since such GE crops were introduced in 1996.2 Glyphosate is also a popular tool for desiccating (or accelerating the drying out) of crops like wheat and oats.

Unbeknownst to many, glyphosate is sprayed onto many crops shortly before harvest, which is why residues have been found in GE and non-GE foods alike. In the documentary above, "Poisoned Fields: Glyphosate, the Underrated Risk?" you can hear why this is so concerning.

While many farmers continue to believe the chemical is relatively benign and using it is safe for their crops and the environment, both the crop fields and the public are being poisoned as a result.

Glyphosate Damages Plant Root Systems, Soil

After farm fields are treated with glyphosate for years, you can see the physical damage that glyphosate causes. After two years, the fields are still green but after 11 years, the video shows drone footage of brown, burned out fields that the farmers reported as mysterious damage.

The fine roots of plants are responsible for taking in nutrients from the soil, but if they're damaged the plant cannot do so efficiently. Not surprisingly, researchers found severely restricted root growth, with far fewer fine roots, among plants growing in the fields treated with glyphosate for more than a decade.

Gunter Neumann, Ph.D., nutritional crop physiologist with the University of Hohenheim in Germany, explained:

"We conducted a state-financed residue analysis for glyphosate and other pesticides. For glyphosate, the data consistently showed that the levels of residue that were present [six] months after the application were as high as one would expect directly after the spring.

Two meters [6.56 feet] over, where the fields were treated for a shorter time, all levels were below the detection limits."

The damage happened slowly, and as such wouldn't have been noticed if the glyphosate-treated fields weren't in such close proximity. Farmers increased fertilizer applications on the damaged fields in the hopes of saving the crops, but it didn't help.

One farmer, who was forced to speak anonymously for fear of retaliation for speaking negatively about glyphosate, found plant viruses increased when he sprayed the chemical.

"On some fields it caused a total yield loss," he said. This was only observed in the areas treated with glyphosate for long periods (longer than two or three years). Neumann noted that advances in molecular biological methods have allowed researchers to detect other types of damage on the crops, including:

• Hormonal disturbances
• Negative effects on physiological processes, including a downregulated stress response
• Genes involved in water intake became less active

Glyphosate is said to work by inhibiting only a single enzyme to kill unwanted plants, but Neumann proved that glyphosate also changes plant genes involved in root growth, water intake and stress resistance.

Glyphosate in Feed Sickens Farm Animals

The documentary also highlights the harm glyphosate exerts on farm animals consuming glyphosate-treated feed. One German pig farmer noticed pigs giving birth to fewer piglets and an increase in stillborn and deformed piglets, which he said increase with the level of glyphosate in the feed.

With glyphosate at levels of 1.30 parts per million (ppm) in the feed, 1 out of 529 piglets were born deformed. At 2.26 ppm, 1 out of 240 piglets were born deformed, a linear increase. Higher doses of glyphosate in the feed were clearly associated with a higher number of deformities in the piglets.

When he switched to glyphosate-free feed, the problems declined. To be sure this wasn't a coincidence, he then switched the pigs back to the glyphosate-treated feed. He noticed the pigs seemed to eat less of the feed and had more diarrhea, which required him to use more antibiotics.

This is a side effect known before, as glyphosate may disrupt the balance of gut microbes in mammals (including humans). Anthony Samsel, Ph.D., research scientist and environmental consultant, and Stephanie Seneff, Ph.D., a research scientist at the Massachusetts Institute of Technology (MIT), explained:

"One likely effect of chronic low-dose oral exposure to glyphosate is a disruption of the balance among gut microbes towards an over-representation of pathogens. This leads to a chronic inflammatory state in the gut, as well as an impaired gut barrier and many other sequelae."

Does Glyphosate Cause Fertility Problems?

The documentary also includes a family dairy farmer in Germany who noticed his cows developed fertility problems after he began supplementing their diets with a concentrated feed that contained glyphosate residues.

It was impossible to purchase a concentrated feed that did not contain residues, and no manufacturer would guarantee the feed would be glyphosate-free.

He then switched to a locally produced feed and experienced dramatic results. Reproduction rates doubled from 30 percent to 60 percent when glyphosate was no longer part of the feed. Disturbingly, it's also been found that glyphosate may affect fertility in humans.

In 2014, a report from the Institute of Science in Society (ISIS) highlighted what appears to be the perfect storm for an "infertility time-bomb," courtesy of glyphosate.3Average sperm counts have dropped by nearly half in the last 50 years, even among men without fertility problems.

Further, ISIS noted, 20 percent of young European men have sperm counts below the World Health Organization (WHO) reference level of 20 m/ml, and 40 percent have levels below 40 m/ml, which is associated with prolonging the time to pregnancy. Meanwhile, rates of conditions that impact semen quality and fertility are also on the rise.

There are, of course, many potential explanations for these conditions, but, as ISIS noted, it has been proposed that an environmental toxicant, especially an endocrine-disrupting chemical such as glyphosate, may be involved.

In December 2013, meanwhile, a study revealed that Roundup exposure induced cell death in Sertoli cells in prepubertal rat testis.4 Sertoli cells are required for male sexual development, including maintaining the health of sperm cells. The exposure was a low dose (36 ppm), which is well within the U.S. Environmental Protection Agency's (EPA) food safety levels.

Glyphosate Led to Tumors in Rats

The International Agency for Research on Cancer (IARC) has determined glyphosate is a probable human carcinogen. Previous research on animals, including rats, has led to similar findings.

In 2012, the first-ever lifetime feeding study evaluating the health risks of glyphosate and GE foods found that rats fed a type of GE corn that is prevalent in the U.S. food supply for two years developed massive mammary tumors, kidney and liver damage, and other serious health problems. According to the authors:5

"The health effects of a Roundup-tolerant genetically modified maize (from 11 [percent] in the diet), cultivated with or without Roundup, and Roundup alone (from 0.1ppb in water), were studied [two] years in rats. In females, all treated groups died [two to three] times more than controls, and more rapidly. This difference was visible in [three] male groups fed GMOs. All results were hormone- and sex-dependent, and the pathological profiles were comparable.

Females developed large mammary tumors almost always more often than and before controls, the pituitary was the second most disabled organ; the sex hormonal balance was modified by GMO and Roundup treatments.

In treated males, liver congestions and necrosis were 2.5 [to] 5.5 times higher ... Marked and severe kidney nephropathies were also generally 1.3 [to] 2.3 greater. Males presented [four] times more large palpable tumors than controls, which occurred up to 600 days earlier."

The findings were a nail in the coffin for the pesticide/biotech industry, but then the journal began to receive Letters to the Editor alleging fraud and calling upon the editors to retract the paper.

After what the journal described as a "thorough and time-consuming analysis" of the study, they said they found "no evidence of fraud or intentional misrepresentation of the data." All they could find "wrong" with the research was that it used a low number of animals, but they, quite outrageously, retracted this important paper nonetheless. Even the retraction statement admits that the results presented are "not incorrect" but rather may be "inconclusive."

How Glyphosate Is Destroying the Soil

Numerous studies have also shown that glyphosate is contributing not only to the huge increase in Sudden Death Syndrome (SDS), a serious plant disease, but also to an outbreak of some 40 different plant and crop diseases. It weakens plants, destroys soil and promotes disease in a number of ways, including:

• Acting as a chelator of vital nutrients, depriving plants of the nutrients necessary for healthy plant function
• Destroying beneficial soil organisms that suppress disease-causing organisms and help plants absorb nutrients
• Interfering with photosynthesis, reducing water use efficiency, shortening root systems and causing plants to release sugars, which changes soil pH
• Stunting and weakening plant growth

The herbicide doesn't destroy plants directly; instead, it creates a unique "perfect storm" of conditions that activates disease-causing organisms in the soil, while at the same time wiping out plant defenses against those diseases.

Glyphosate Detected in Urine and Breastmilk

Laboratory testing commissioned by the organizations Moms Across America and Sustainable Pulse revealed that glyphosate is now showing up virtually everywhere.

The analysis revealed glyphosate in levels of 76 μg/L to 166 μg/L in women's breast milk. As reported by The Detox Project, this is 760 to 1,600 times higher than the EU-permitted level in drinking water (although it's lower than the U.S. maximum contaminant level for glyphosate, which is 700 μg/L.).6

This dose of glyphosate in breastfed babies' every meal is only the beginning. An in vitro study designed to simulate human exposures also found that glyphosate crosses the placental barrier. In the study, 15 percent of the administered glyphosate reached the fetal compartment.7

The documentary also features the director and founder of Moms Across America, who states they found glyphosate in her son's urine around the same time as the onset of symptoms of autism.

Seneff has also pointed out correlations between increased glyphosate use over recent years and skyrocketing autism rates.She identified two key problems in autism that are unrelated to the brain yet clearly associated with the condition — both of which are linked with glyphosate exposure:

• Gut dysbiosis (imbalances in gut bacteria, inflammation, leaky gut and food allergies such as gluten intolerance)
• Disrupted sulfur metabolism / sulfur and sulfate deficiency

Interestingly, certain microbes in your body actually break down glyphosate, which is a good thing. However, a byproduct of this action is ammonia, and children with autism tend to have significantly higher levels of ammonia in their blood than the general population.

Glyphosate Far More Restricted in Europe Than in the US

European Commission leaders met in March 2016 to vote on whether to renew a 15-year license for glyphosate, which was set to expire in June. The decision was tabled amid mounting opposition, as more than 180,000 Europeans signed a petition calling for glyphosate to be banned outright. Ultimately, more than 2 million signatures were collected against relicensing the chemical.

In June, however, the European Commission granted an 18-month extension to glyphosate while they continue the review. A ruling is expected by the end of 2017. In the meantime, new restrictions were announced in the interim, including a ban on a co-formulant (tallowamine), increased scrutiny of pre-harvest uses of glyphosate and efforts to minimize its use in public parks and playgrounds.

Unlike in the U.S., where glyphosate use is largely unrestricted, "seven EU states have extensive glyphosate prohibitions in place, two have restrictions and four countries have impending or potential bans," The Guardian reported.8

Test Your Personal Glyphosate Levels

If you'd like to know your personal glyphosate levels, you can now find out, while also participating in a worldwide study on environmental glyphosate exposures. The Health Research Institute (HRI) in Iowa developed the glyphosate urine test kit, which will allow you to determine your own exposure to this toxic herbicide.

Ordering this kit automatically allows you to participate in the study and help HRI better understand the extent of glyphosate exposure and contamination. In a few weeks, you will receive your results, along with information on how your results compare with others and what to do to help reduce your exposure. We are providing these kits to you at no profit in order for you to participate in this environmental study.

In the meantime, eating organic as much as possible and investing in a good water filtration system for your home are among the best ways to lower your exposure to glyphosate and other pesticides. In the case of glyphosate, it's also wise to avoid desiccated crops like wheat and oats.

http://articles.mercola.com/sites/articles/archive/2016/12/24/poisoned-field-glyphosate-underrated-risk.aspx

MUST READ: This Vegetable Stalks Aging and Cancer Like a Guard Dog

Think you have no power to stop aging, defy your genes or influence your longevity? Here's one terrific food that can detoxify carcinogens, repair your cells, slow weight gain and put the brakes on aging. Experience all the 'wow' you deserve, no matter your age or stage.

Broccoli May Slow Age-Related Decline and Promote Longevity by Reducing Chronic Health Risks

November 14, 2016 

Story at-a-glance

• An enzyme found in broccoli may slow age-related decline in health by improving mitochondrial health and restoring your metabolism to more youthful levels
• Broccoli has been shown to reduce your risk of many common diseases including arthritis, cancer, high blood pressure, heart disease, kidney disease, fatty liver disease and diabetes
• Sulforaphane, a naturally occurring organic sulfur compound found in broccoli has potent anti-cancer activity; it may also be helpful for children with autism

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By Dr. Mercola

Eating plenty of fresh vegetables (ideally organic to avoid pesticides) is a foundational aspect of a healthy diet, and can help lower your risk for many chronic diseases, including type 2 diabetes,1 heart disease, stroke and certain cancers.

Besides being rich in vitamins, minerals and fiber, vegetables also contain antioxidants and disease-fighting compounds you won’t find in other foods, especially not processed foods.

Some phytochemicals (plant chemicals) help reduce inflammation and eliminate carcinogens, while others regulate cell reproduction, apoptosis (programmed cell death) and DNA maintenance.

Certain plant compounds also have potent anti-aging effects. Broccoli, for example, which is probably best known for its anti-cancer activity, also contains an enzyme researchers believe may slow age-related decline in health by restoring your metabolism to more youthful levels.2,3,4

One basic premise of aging is that, as you age, your cells’ ability to produce energy declines. With less available energy, cell repair and maintenance declines as well and, with that, degeneration sets in.

Broccoli Enzyme May Slow Aging

The enzyme in question is called nicotinamide mononucleotide (NMN), which plays a role in producing nicotinamide adenine dinucleotide (NAD), a compound involved in mitochondrial health and energy metabolism.

Previous research has shown that, with age, your body loses its capacity to create NAD — an effect thought to be related to, or the result of, chronic inflammation. Studies have shown that taking NAD directly is ineffective, however, which is what led the researchers to look for a precursor.

Indeed, they found that when NMN is dissolved and administered in water, it takes just three minutes for the compound to appear in the blood. Once there, the NMN is quickly converted into NAD in multiple tissues. As reported by Time magazine:5

“When they gave normal aging mice infusions of NMN, they made more of that energy-fueling compound and some of the biological problems associated with aging went away.

The NMN-treated animals did not gain as much weight, they were able to convert food into energy more efficiently, their blood sugar was better — even their eyesight improved.

The mice receiving NMN were also able to prevent some of the genetic changes associated with aging.”

Eat Your Greens If You Want Health and Longevity

The results were encouraging enough that the researchers are now planning further studies in humans, using NMN supplements. As explained by senior author Dr. Shin-Ichiro Imai, professor of developmental biology and medicine at Washington University:6

“We are losing the enzyme NMN. But if we can bypass that process by adding NMN, we can make energy again. These results provide a very important foundation for the human studies.”

Besides broccoli, NMN is also found in cucumbers, cabbage, avocado and other green vegetables. While it remains to be seen whether all of these effects hold true in humans, it certainly wouldn’t hurt to add more greens to your diet. Overall, studies have shown that people with higher vegetable intake have:

Lower risks of high blood pressure and stroke	Lower risks of certain types of cancer	Reduced risk of kidney stones and bone loss
Higher scores on cognitive tests	Higher antioxidant levels	Lower biomarkers for oxidative stress
Lower risk for Alzheimer’s disease7	Lower risk for eye diseases	Fewer digestive problems

The Role of NAD and Adipose Tissue in Whole Body Energy Metabolism

A related study8 by this research team, published in August 2016, revealed more about NAD’s influence on glucose metabolism and body fat specifically. As reported by Science Daily: 9

“In that study, the mice had a defect in the ability to manufacture NAD only in the body's fat tissue. The rest of their tissues and organs were normal.

‘Even though NAD synthesis was stopped only in the fat tissue, we saw metabolic dysfunction throughout the body, including the skeletal muscle, the heart muscle, the liver and in measures of the blood lipids,’ Yoshino said.

‘When we gave NMN to these mice, these dysfunctions were reversed. That means NAD in adipose tissue is a critical regulator of whole body metabolism.’

Added Imai, ‘This is important because … if you mess up NAD synthesis only in fat tissue, you see insulin resistance everywhere. Adipose tissue must be doing something remarkable to control whole body insulin sensitivity.’"

Broccoli Provides Many Health Benefits

Broccoli is one of the most widely studied foods, and research has revealed a long list of health benefits associated with this cruciferous vegetable, including a reduced risk for:10

Osteoarthritis11,12,13,14	Cancer
High blood pressure15	Heart disease
Kidney disease16	Diabetes17
Neurodegenerative diseases18	Allergies19

Broccoli and other water- and nutrient-rich veggies also support healthy liver function, which in turn promotes optimal functioning of your natural detoxification systems. Broccoli sprouts, in particular, have been shown to help detox environmental pollutants such as benzene.20,21,22

This is important for virtually everyone these days, but especially women of childbearing age. Autistic children are known to have higher levels of environmental toxins in their system, and this underlying toxic burden plays a significant role. Healthy liver function also helps promote healthy, beautiful skin, making broccoli a good anti-aging food. What’s more, the sulforaphane in broccoli also helps repair skin damage.

The sulforaphane found in broccoli also helps raise testosterone levels, inhibits the retention of body fat and helps protect your muscles against exercise-induced damage.23

Broccoli — A Good Source of Healthy Fiber

Broccoli contains an array of beneficial compounds, including fiber, which is broken down into short-chain fatty acids (SCFAs) by your gut bacteria. SCFAs, in turn, have been shown to lessen your risk of inflammatory diseases.24 Your liver converts SCFAs into ketones that nourish your body and perform important signaling functions. Fiber also promotes health by nourishing beneficial gut bacteria, and by activating a gene called T-bet, which is essential for producing immune cells in the lining of your digestive tract.25

These immune cells, called innate lymphoid cells (ILCs), help maintain balance between immunity and inflammation in your body and produce interleukin-22 (IL-22), a hormone that helps protect your body from pathogenic bacteria. ILCs even help resolve cancerous lesions and prevent the development of bowel cancers and other inflammatory diseases.

The Anti-Cancer Effects of Sulforaphane

As mentioned, broccoli is perhaps most well-known for its anti-cancer activity, an effect attributed to a naturally occurring sulfur compound called sulforaphane. Broccoli sprouts are the most potent in this regard. Three-day-old broccoli sprouts can contain anywhere from 20 to 50 times the amount of chemoprotective compounds found in mature broccoli.26,27

Some researchers have suggested broccoli may be a key part of an anti-cancer diet.28 Judging by the following study results, chances are broccoli may certainly improve your odds of dodging a dreaded cancer diagnosis.

• In one study, three or four servings (about 10 spears) of broccoli per week was found to reduce men’s risk of prostate cancer by more than 60 percent.29,30
• Higher intake of cruciferous vegetables such as broccoli also lowered the risk of bladder cancer in men by as much as 50 percent.31
• Men with detectable amounts of isothiocyanates (sulfur compounds such as sulforaphane) in their bodies had a 36 percent lower chance of developing lung cancer over 10 years.32
• Eating broccoli three to five times per week has been shown to lower the risk of liver cancer, and help prevent the development of nonalcoholic fatty liver disease (NAFLD)33,34,35,36,37

There are a number of mechanisms behind this anti-cancer effect. Research has shown sulforaphane:

Can kill cancer stem cells, thereby slowing tumor growth.	Helps detoxify carcinogens.38
Causes apoptosis in colon,39 prostate,40 breast41 and tobacco-induced lung cancer42 cells.	Reduces the number of reactive oxygen species (ROS), molecules that cause cell damage, by as much as 73 percent.43
Plays a role in activating more than 200 different genes, activating some genes that fight cancer and switching off others that fuel tumors.44	Normalizes DNA methylation, which plays a role in a number of diseases, including hypertension, kidney function,45 gut health46 and cancer. DNA methylation47 is the process by which a methyl group is added to part of a DNA molecule. This is a crucial part of normal cell function as it allows cells to “remember who they are and where they have been.” DNA methylation also suppresses viral- and other disease-related gene expression.

Sulforaphane May Benefit Autistic Children

Sulforaphane influences bacteria as well. For example, broccoli sprouts have been shown to inhibit Helicobacter pylori (H. pylori), the bacteria thought to cause gastric ulcers. Interestingly, H. pylori may also play a role in autism. Gastrointestinal (GI) problems are common among autistic children, and those with the worst GI problems often have more severe autism.

Preliminary research suggests sulforaphane may improve verbal communication and decrease repetitive behaviors in those with autism.48 This effect is thought to be related to sulforaphane’s ability to trigger a heat-shock response — a biological effect that protects cells from stress during a fever. Previous research has shown that, in some autistic people, repetitive behaviors decline during fevers. In this study, 80 percent of the participants had a history of this fever effect.

Positive results from sulforaphane were observed within as little as four weeks. Communication improved, as did symptoms of hyperactivity and irritability. By the end of the 18-week study, about 50 percent of those receiving sulforaphane experienced improved ability to interact socially.

However, about one-third of the treatment group did not have any noticeable results, so more research needs to be done to ascertain how and why the compound works in certain cases. That said, the study still supports the notion that food is an important part of the treatment plan for autism, and can have a significant impact on behavior.

I believe part of the reason for its beneficial effect on autistic symptoms may be related to its ability to affect gene expression, inhibit detrimental gut bacteria and promote detoxification of harmful environmental pollutants. All of these factors play a role in autism, and pretty much anything that will have a beneficial effect on them is likely to be useful to some degree.

Other Health-Promoting Compounds Found in Broccoli

While sulforaphane typically receives the most attention, broccoli also contains a number of other health-promoting compounds, including:

•Glucoraphanin, a glucosinolate precursor of sulforaphane that also influences the process of carcinogenesis and mutagenesis.49,50 Compared to mature broccoli, broccoli sprouts can contain up to 20 times more glucoraphanin.

•Phenolic compounds, including flavonoids and phenolic acids, which have a potent ability to eliminate damaging free radicals and quell inflammation,51,52,53 resulting in a lower risk for diseases such as asthma, type 2 diabetes and heart disease.54

One of the ways phenolic compounds slow the encroachment of disease is by defending against infection, most dramatically by zapping ROS linked to atherosclerosis and neurodegenerative diseases such as Parkinson’s and Alzheimer’s.

•Diindolylmethane (DIM). Your body produces DIM when it breaks down cruciferous vegetables. Like many other broccoli compounds, DIM has shown multiple potential benefits, including boosting your immune system and helping to prevent or treat cancer.55,56

•Vitamins and minerals. Broccoli has twice the vitamin C of an orange, and almost as much calcium as whole milk (with a better rate of absorption). It also contains folate and iron, and all of these nutrients are important for a healthy pregnancy.

Lightly Steam Your Broccoli to Boost Sulforaphane Content

Like many others, I was never a big fan of broccoli. That all changed once I learned how to cook it properly. After avoiding it for years, I now eat it regularly. The “secret” to cooking broccoli is to lightly steam it. Not only will it taste better this way, but it will also optimize its nutritional value.

When you eat raw mature broccoli, you only get about 12 percent of the total sulforaphane content theoretically available based on the parent compound. In the video above, Elizabeth Jeffery, Ph.D., a researcher and professor in the Department of Food Science and Human Nutrition at the University of Illinois, explains the research57 showing that steaming your broccoli for three to four minutes is ideal. Do not go past five minutes.

Steaming your broccoli spears for three to four minutes will optimize the sulforaphane content by eliminating epithiospecifier protein — a heat-sensitive sulfur-grabbing protein that inactivates sulforaphane — while still retaining the enzyme myrosinase, which converts glucoraphanin to sulforaphane. Without it, you cannot get any sulforaphane.

Boiling or microwaving your broccoli past the one-minute mark is NOT recommended, as it will destroy a majority of the myrosinase. If you want to boil your broccoli, blanch it in boiling water for no more than 20 to 30 seconds, then immerse it in cold water to stop the cooking process. Also beware that frozen broccoli has diminished ability to produce sulforaphane as the enzyme myrosinase,58 which converts glucoraphanin to sulforaphane, is quickly destroyed during the blanching process.59

So ideally, use fresh broccoli. The sulforaphane content can be further optimized by adding a myrosinase-containing food to it,60such as:

• Mustard seed61
• Daikon radishes
• Wasabi
• Arugula
• Cole slaw

Adding a myrosinase-rich food is particularly important if you do not steam or flash-blanche raw broccoli. As mentioned, frozen broccoli typically has a reduced amount of myrosinase as it’s already been blanched as part of the processing. Boiling or microwaving it further can easily lead to it being more or less devoid of sulforaphane. So if you’re using frozen broccoli, be sure to add a food that contains myrosinase (see list above).

Another option is to eat broccoli sprouts. They don’t need to be cooked, and are FAR more potent than whole broccoli, allowing you to eat far less in terms of quantity.

http://articles.mercola.com/sites/articles/archive/2016/11/14/health-benefits-broccoli.aspx

See also:

1. MUST READ: This vegetable defeats cancer at the genetic level
2. MUST READ: This Vegetable Stalks Aging and Cancer Like a Guard Dog
3. Cabbage - A super alternative to brocolli
4. The secret to staying young is broccoli and cabbage.
5. The Remarkable Health Benefits of Broccoli, and How to Maximize Its Cancer-Fighting Potential
6. Your broccoli doesn’t have much nutritional value if you don’t do this
7. MUST READ: More Reasons to Eat Your Broccoli
8. 10 Health Benefits of Brocolli