Alzheimer’s gut bacteria, virus and iron dysregulation

Researchers Identify Virus and Two Types of Bacteria as Major Causes of Alzheimer’s

A worldwide team of senior scientists and clinicians have come together to produce an editorial which indicates that certain microbes – a specific virus and two specific types of bacteria – are major causes of Alzheimer’s Disease. Their paper, which has been published online in the highly regarded peer-reviewed journal, Journal of Alzheimer’s Disease, stresses the urgent need for further research – and more importantly, for clinical trials of anti-microbial and related agents to treat the disease.

This major call for action is based on substantial published evidence into Alzheimer’s. The team’s landmark editorial summarises the abundant data implicating these microbes, but until now this work has been largely ignored or dismissed as controversial – despite the absence of evidence to the contrary. Therefore, proposals for the funding of clinical trials have been refused, despite the fact that over 400 unsuccessful clinical trials for Alzheimer’s based on other concepts were carried out over a recent 10-year period.

Opposition to the microbial concepts resembles the fierce resistance to studies some years ago which showed that viruses cause certain types of cancer, and that a bacterium causes stomach ulcers. Those concepts were ultimately proved valid, leading to successful clinical trials and the subsequent development of appropriate treatments.

Professor Douglas Kell of The University of Manchester’s School of Chemistry and Manchester Institute of Biotechnology is one of the editorial’s authors. He says that supposedly sterile red blood cells were seen to contain dormant microbes, which also has implications for blood transfusions.

“We are saying there is incontrovertible evidence that Alzheimer’s Disease has a dormant microbial component, and that this can be woken up by iron dysregulation. Removing this iron will slow down or prevent cognitive degeneration – we can’t keep ignoring all of the evidence,” Professor Douglas Kell said.

Image shows an old lady looking out of a window.

Professor Resia Pretorius of the University of Pretoria, who worked with Douglas Kell on the editorial, said “The microbial presence in blood may also play a fundamental role as causative agent of systemic inflammation, which is a characteristic of Alzheimer’s disease – particularly, the bacterial cell wall component and endotoxin, lipopolysaccharide. Furthermore, there is ample evidence that this can cause neuroinflammation and amyloid-β plaque formation.”

The findings of this editorial could also have implications for the future treatment of Parkinson’s Disease, and other progressive neurological conditions.

ABOUT THIS ALZHEIMER’S DISEASE RESEARCH

Source: University of Manchester
Image Credit: The image is adapted from the University of Manchester press release.
Original Research: Full open access editorial for “Microbes and Alzheimer’s Disease” by Itzhaki, Ruth F.; Lathe, Richard; Balin, Brian J.; Ball, Melvyn J.; Bearer, Elaine L.; Bullido, Maria J.; Carter, Chris; Clerici, Mario; Cosby, S. Louise; Field, Hugh; Fulop, Tamas; Grassi, Claudio; Griffin, W. Sue T.; Haas, Jürgen; Hudson, Alan P.; Kamer, Angela R.; Kell, Douglas B.; Licastro, Federico; Letenneur, Luc; Lövheim, Hugo; Mancuso, Roberta; Miklossy, Judith; Lagunas, Carola Otth; Palamara, Anna Teresa; Perry, George; Preston, Christopher; Pretorius, Etheresia; Strandberg, Timo; Tabet, Naji; Taylor-Robinson, Simon D.; and Whittum-Hudson, Judith A. in Journal of Alzheimer’s Disease. Published online March 8 2016 doi:10.3233/JAD-160152


Abstract

Microbes and Alzheimer’s Disease

We are researchers and clinicians working on Alzheimer’s disease (AD) or related topics, and we write to express our concern that one particular aspect of the disease has been neglected, even though treatment based on it might slow or arrest AD progression. We refer to the many studies, mainly on humans, implicating specific microbes in the elderly brain, notably herpes simplex virus type 1 (HSV1), Chlamydia pneumoniae, and several types of spirochaete, in the etiology of AD. Fungal infection of AD brain [5, 6] has also been described, as well as abnormal microbiota in AD patient blood. The first observations of HSV1 in AD brain were reported almost three decades ago]. The ever-increasing number of these studies (now about 100 on HSV1 alone) warrants re-evaluation of the infection and AD concept.

AD is associated with neuronal loss and progressive synaptic dysfunction, accompanied by the deposition of amyloid-β (Aβ) peptide, a cleavage product of the amyloid-β protein precursor (AβPP), and abnormal forms of tau protein, markers that have been used as diagnostic criteria for the disease. These constitute the hallmarks of AD, but whether they are causes of AD or consequences is unknown. We suggest that these are indicators of an infectious etiology. In the case of AD, it is often not realized that microbes can cause chronic as well as acute diseases; that some microbes can remain latent in the body with the potential for reactivation, the effects of which might occur years after initial infection; and that people can be infected but not necessarily affected, such that ‘controls’, even if infected, are asymptomatic

“Microbes and Alzheimer’s Disease” by Itzhaki, Ruth F.; Lathe, Richard; Balin, Brian J.; Ball, Melvyn J.; Bearer, Elaine L.; Bullido, Maria J.; Carter, Chris; Clerici, Mario; Cosby, S. Louise; Field, Hugh; Fulop, Tamas; Grassi, Claudio; Griffin, W. Sue T.; Haas, Jürgen; Hudson, Alan P.; Kamer, Angela R.; Kell, Douglas B.; Licastro, Federico; Letenneur, Luc; Lövheim, Hugo; Mancuso, Roberta; Miklossy, Judith; Lagunas, Carola Otth; Palamara, Anna Teresa; Perry, George; Preston, Christopher; Pretorius, Etheresia; Strandberg, Timo; Tabet, Naji; Taylor-Robinson, Simon D.; and Whittum-Hudson, Judith A. in Journal of Alzheimer’s Disease. Published online March 8 2016 doi:10.3233/JAD-160152

Gut microbes eat our medication for Parkinson

Pills illustration (stock image).
Credit: © georgejmclittle / Adobe Stock
Researchers have discovered one of the first concrete examples of how the microbiome can interfere with a drug’s intended path through the body. Focusing on levodopa (L-dopa), the primary treatment for Parkinson’s disease, they identified which bacteria out of the trillions of species is responsible for degrading the drug and how to stop this microbial interference.

The first time Vayu Maini Rekdal manipulated microbes, he made a decent sourdough bread. At the time, young Maini Rekdal, and most people who head to the kitchen to whip up a salad dressing, pop popcorn, ferment vegetables, or caramelize onions, did not consider the crucial chemical reactions behind these concoctions.

Even more crucial are the reactions that happen after the plates are clean. When a slice of sourdough travels through the digestive system, the trillions of microbes that live in our gut help the body break down that bread to absorb the nutrients. Since the human body cannot digest certain substances — all-important fiber, for example — microbes step up to perform chemistry no human can.

“But this kind of microbial metabolism can also be detrimental,” said Maini Rekdal, a graduate student in the lab of Professor Emily Balskus and first-author on their new study published in Science. According to Maini Rekdal, gut microbes can chew up medications, too, often with hazardous side effects. “Maybe the drug is not going to reach its target in the body, maybe it’s going to be toxic all of a sudden, maybe it’s going to be less helpful,” Maini Rekdal said.

In their study, Balskus, Maini Rekdal, and their collaborators at the University of California San Francisco, describe one of the first concrete examples of how the microbiome can interfere with a drug’s intended path through the body. Focusing on levodopa (L-dopa), the primary treatment for Parkinson’s disease, they identified which bacteria are responsible for degrading the drug and how to stop this microbial interference.

Parkinson’s disease attacks nerve cells in the brain that produce dopamine, without which the body can suffer tremors, muscle rigidity, and problems with balance and coordination. L-dopa delivers dopamine to the brain to relieve symptoms. But only about 1 to 5% of the drug actually reaches the brain.

This number — and the drug’s efficacy — varies widely from patient to patient. Since the introduction of L-dopa in the late 1960s, researchers have known that the body’s enzymes (tools that perform necessary chemistry) can break down L-dopa in the gut, preventing the drug from reaching the brain. So, the pharmaceutical industry introduced a new drug, carbidopa, to block unwanted L-dopa metabolism. Taken together, the treatment seemed to work.

“Even so,” Maini Rekdal said, “there’s a lot of metabolism that’s unexplained, and it’s very variable between people.” That variance is a problem: Not only is the drug less effective for some patients, but when L-dopa is transformed into dopamine outside the brain, the compound can cause side effects, including severe gastrointestinal distress and cardiac arrhythmias. If less of the drug reaches the brain, patients are often given more to manage their symptoms, potentially exacerbating these side effects.

Maini Rekdal suspected microbes might be behind the L-dopa disappearance. Since previous research showed that antibiotics improve a patient’s response to L-dopa, scientists speculated that bacteria might be to blame. Still, no one identified which bacterial species might be culpable or how and why they eat the drug.

So, the Balskus team launched an investigation. The unusual chemistry — L-dopa to dopamine — was their first clue.

Few bacterial enzymes can perform this conversion. But, a good number bind to tyrosine — an amino acid similar to L-dopa. And one, from a food microbe often found in milk and pickles (Lactobacillus brevis), can accept both tyrosine and L-dopa.

Using the Human Microbiome Project as a reference, Maini Rekdal and his team hunted through bacterial DNA to identify which gut microbes had genes to encode a similar enzyme. Several fit their criteria; but only one strain, Enterococcus faecalis (E. faecalis), ate all the L-dopa, every time.

With this discovery, the team provided the first strong evidence connecting E. faecalis and the bacteria’s enzyme (PLP-dependent tyrosine decarboxylase or TyrDC) to L-dopa metabolism.

And yet, a human enzyme can and does convert L-dopa to dopamine in the gut, the same reaction carbidopa is designed to stop. Then why, the team wondered, does the E. faecalis enzyme escape carbidopa’s reach?

Even though the human and bacterial enzymes perform the exact same chemical reaction, the bacterial one looks just a little different. Maini Rekdal speculated that carbidopa may not be able to penetrate the microbial cells or the slight structural variance could prevent the drug from interacting with the bacterial enzyme. If true, other host-targeted treatments may be just as ineffective as carbidopa against similar microbial machinations.

But the cause may not matter. Balskus and her team already discovered a molecule capable of inhibiting the bacterial enzyme.

“The molecule turns off this unwanted bacterial metabolism without killing the bacteria; it’s just targeting a non-essential enzyme,” Maini Rekdal said. This and similar compounds could provide a starting place for the development of new drugs to improve L-dopa therapy for Parkinson’s patients.

The team might have stopped there. But instead, they pushed further to unravel a second step in the microbial metabolism of L-dopa. After E. faecalis converts the drug into dopamine, a second organism converts dopamine into another compound, meta-tyramine.

To find this second organism, Maini Rekdal left behind his mother dough’s microbial masses to experiment with a fecal sample. He subjected its diverse microbial community to a Darwinian game, feeding dopamine to hordes of microbes to see which prospered.

Eggerthella lenta won. These bacteria consume dopamine, producing meta-tyramine as a by-product. This kind of reaction is challenging, even for chemists. “There’s no way to do it on the bench top,” Maini Rekdal said, “and previously no enzymes were known that did this exact reaction.”

The meta-tyramine by-product may contribute to some of the noxious L-dopa side effects; more research needs to be done. But, apart from the implications for Parkinson’s patients, E. lenta’s novel chemistry raises more questions: Why would bacteria adapt to use dopamine, which is typically associated with the brain? What else can gut microbes do? And does this chemistry impact our health?

“All of this suggests that gut microbes may contribute to the dramatic variability that is observed in side effects and efficacy between different patients taking L-dopa,” Balskus said.

But this microbial interference may not be limited to L-dopa and Parkinson’s disease. Their study could shepherd additional work to discover exactly who is in our gut, what they can do, and how they can impact our health, for better or worse.

Story Source:

Materials provided by Harvard University. Original written by Caitlin McDermott-Murphy. Note: Content may be edited for style and length.

Keeping our brain healthy from birth to 100

Keeping our brain healthy from birth to 100

December 1,2018 at JCC in Palo Alto California

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Tips for healthy brain

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Treating acid reflux naturally by WikiHow

Hyperacidity, as known as acid reflux or heartburn, is the irritation of the esophagus that results when acid from the stomach is released into the esophagus.

This occurs because of a dysfunction in a muscular valve, known as the lower esophageal sphincter (LES), which normally keeps stomach acid in the stomach. The LES may open too often or it may not close tightly enough, allowing stomach acid to leak through. Acid reflux isn’t a serious medical problem unless it becomes constant and chronic, in which case it becomes GastroEsophageal Reflux Disease (GERD) and requires treatment.[1] If you follow a few simple steps, you can diagnose acid reflux and learn to treat it naturally.
See When Should You Try This? to learn more about when natural remedies for acid reflux might be most beneficial.

 Using Lifestyle Modifications for Acid Reflux

Change the way you eat. You can change the types and amounts of foods you eat in order to make your acid reflux better. Decrease the amount of food you eat at any one time. This reduces the stress pressure on your stomach. Don’t eat for 2-3 hours before bedtime in order to reduce the risk of food putting pressure on the LES as you try to sleep.
    • Try to eat slowly because it allows the food to be digested more easily and quickly, leaving less food in the stomach adding pressure on the LES.[2]
  1. Avoid food and beverage triggers. You need to figure out exactly what kinds of food trigger your acid reflux. Start keeping track of foods and beverages you eat and note any that cause you any problems. Use a common triggers list to begin with and add any foods or beverages that you know you are sensitive to. If any food you eat bothers you an hour later, you should eliminate that food from your diet.

    • For example, if you eat spaghetti and meatballs with tomato sauce for dinner and experience acid reflux within an hour, your trigger could be the spaghetti, the meatballs, or the tomato sauce. Next time, eliminate the tomato sauce. If you have no hyperacidity, you know that the tomato sauce is the trigger. If you still do, it could be the pasta or the meatballs. Next day, have some leftover pasta alone with no meatballs and no sauce. If you have hyperacidity, the pasta should be eliminated from your diet.[3]
  2. Shift your habits. There are certain things you can change in your everyday habits that can help with your acid reflux as well. Wear clothing that doesn’t constrict your stomach or abdomen. This causes unnecessary pressure on your stomach, which can cause acid reflux. You should also stop smoking because it increases the amount of acid in your stomach.

    • Try to lose weight, especially if you are severely overweight or obese. This will help reduce pressure on the LES and relieve your acid reflux.[4]
  3. Rethink the way you sleep. Some people have bad acid reflux overnight. If you have this problem, raise the entire head of the bed to allow gravity to help keep the acid in your stomach. This way, the acid will not creep into your esophagus overnight and cause you problems.

    • Piling up pillows won’t really help much as these tend to bend your neck and body in such a way that it actually increases the pressure and makes the hyperacidity worse.[5]

Using Herbal Remedies for Acid Reflux

  1. Talk to your doctor first. There a number of different herbal approaches to treat hyperacidity, but you need to be careful. Talk to your physician first before trying these remedies. In general, natural remedies are very safe, but it is best to be certain they are safe for you. Combining these herbal approaches with the lifestyle modifications should significantly improve how you feel on a daily basis.

    • If you are pregnant, speak to your physician about using any of the herbs to ensure they won’t hurt your baby. [6]
  2. Drink aloe vera juice. Aloe vera is not just good for the outside of your body. Aloe vera juice has many healing qualities as well. Buy organic aloe vera juice. Pour 1/2 cup into a glass and drink. You can sip this multiple times throughout the day, but since aloe vera can act as a laxative, you may want to limit it to a total of 1-2 cups a day.

    • Aloe juice decreases inflammation and acts to neutralize the stomach acid. [7]
  3. Try apple cider vinegar. Although it may seem counter-intuitive, you can use apple cider vinegar to help with acid reflux. Add 1 tablespoon of organic apple cider vinegar to 6 ounces of water. Stir it together well and drink. The vinegar doesn’t have to be organic, but only use apple cider vinegar.

    • Other vinegars don’t work as well and can end up making your problem worse.[8]
  4. Make citrus water. You can use citrus fruits to make a drink similar to lemonade or limeade that will help with your acid reflux. Squeeze a few teaspoons of pure lemon or lime juice and add water to taste. Add a bit of honey or a tiny bit of stevia, a natural sweetener, to the drink if you want to make it a little sweater. Drink this before, during, and after meals.

    • To make the drink more interesting, you can add both kinds of juices if you want.
    • The extra acid in the juices tell your body that it can shut down acid production by a process called feedback inhibition.[9]

  5. Consume more apples. Just as the old saying goes, you should eat at least one apple a day. Apples are very good for you and help to calm acid reflux. The pectin in the apple skin acts as a natural antacid.[10]

    • If you don’t like eating plain apples, try adding them to a salad or putting them in a smoothie.
  6. Drink ginger tea. Ginger acts as an anti-inflammatory and a soothing agent for the stomach. It can also help with nausea and vomiting. To make your own ginger tea, cut up about 1 teaspoon of fresh ginger and add it to boiling water. Let the mixture steep for about 5 minutes. Pour it into a mug and drink.

    • Do this anytime during the day, but especially about 20-30 minutes before meals.
    • You can buy ginger tea bags if you don’t have any fresh ginger.[11][12]
  7. Try other types of tea. You can make a few other varieties of tea to help with your acid reflux. Fennel helps settle the stomach and decreases the acid levels. To make fennel tea, crush about a teaspoon of fennel seeds and add it to a cup of boiled water. Add honey or some stevia to taste and drink 2-3 cups a day about 20 minutes before meals.

    • You can also use mustard seeds or powder to make a tea. Mustard acts as an anti-inflammatory and as an acid neutralizer. You can dissolve it in water to make a tea. If you are up to it, you can take 1 teaspoon of mustard by mouth.
    • You can also try chamomile tea to calm the stomach and act as an anti-inflammatory agent. You can buy chamomile tea in bags or as loose leaf tea.[13]
  8. Take other herbal remedies. There are a few other herbs that can be taken to help your acid reflux. Deglycyrrhizinated licorice root (DGL) works very well to heal the stomach and control hyperacidity. It comes as chewable tablets, but bear in mind that the taste might take some getting used to. The standard dose of DGL is 2-3 tablets every 4-6 hours.

    • Try some slippery elm, which you can have either as 3-4 ounce drink or as a tablet. It coats and soothes irritated tissues. Slippery elm is considered safe in pregnancy.
    • Make sure to follow the manufacturer’s instructions.[14][15]

Trying Other Home Remedies for Acid Reflux

  1. Make a baking soda drink. Baking soda is a base, which means it helps counteract the effects of acid. This holds true for the acid in your stomach. To make this drink, dissolve a teaspoon of baking soda in about 6 ounces of water. Stir it well and drink. It is very effective in neutralizing the acid.

    • Make sure you get baking soda and not baking powder. Baking powder is not nearly as effective.[16]

  2. Chew gum. After you eat, pop in a piece of sugar-free gum. This appears to work because chewing the gum stimulates the salivary glands, which releases bicarbonate into the saliva. The bicarbonate help neutralize the acid in your stomach.[17]

    • Don’t chew sugary gum because it may contribute to the acid in your stomach.
    • Do not chew gum on an empty stomach.
    • You can also chew mastic gum. Mastic gum is made from a resin of the mastic tree, known as Pistacia lentiscus. It has antibacterial properties and has been used to kill the H. pylori infection often associated with peptic ulcers or too much stomach acid.[18]
  3. Attempt the heel drop. There is a chiropractic approach that is used to treat hiatal hernias that is also effective for acid reflux. Drink a 6 to 8 ounce glass of slightly warm water the moment you get out of bed in the morning. While you are standing, bring your arms straight out to the sides and bend them at the elbows. Then, bring both hands in to meet at your chest. Stand up high on your toes, then drop down on your heels. Repeat 10 times.

    • After the 10th drop, keeping your arms up, pant in short, quick, shallow breaths for 15 seconds. Repeat every morning until you get relief.
    • This process seems to realign your stomach and diaphragm, so the hernia does not interfere with your esophagus.[19]
  4. Use coconut oil. Coconut oil has antibacterial properties that help stop acid reflux. This may be the reason that chronic H. pylori stomach infections respond quite well to this simple home remedy. The bacterium H. pylori is often associated with reflux esophagitis.

    • Take 1/2 a tablespoon of coconut oil in warm orange juice, or directly by mouth if you can, three times daily. You can work this up to one to two tablespoons of coconut oil three times daily.
    • Stop three days after your symptoms have subsided.[20]

  5. Eat probiotics. Probiotics are mixtures of a variety of bacteria normally found in your gut, which may include saccharomyces boulardii yeast, cultures of lactobacillus, and bifidobacterium. These good bacteria tend to improve overall well being, help with stomach health, and are all naturally found in your intestines.

    • You can easily get probiotics by eating yogurt with active cultures in it. You can also take a supplement, though make sure you follow the manufacturer’s warnings.[21]

Managing Stress to Help Acid Reflux

  1. Take quiet time. Stress, especially chronic stress, has been linked to acid reflux. To help with your condition, you need to destress everyday. To relax, go into a quiet room or a quiet space outside and breathe deeply for a few minutes. Inhale through your nose slowly, and exhale through your mouth. Take twice as long to exhale as you do to inhale. If you have trouble keeping straight how long you breath, counting can be helpful. Inhale for the count of 6 to 8 counts and exhale, counting to 12 to 16. Repeat as often as you can.[22]

  2. Try progressive muscle relaxation. Since stress is such a common problem, the American Psychological Association (APA) has come up with multiple ways to help you relax. They suggest progressive muscle relaxation. For this exercise, stand straight up. Contract the muscles in your feet and lower legs, tightening them as much as possible for 30 seconds. After this amount of time, slowly release the tension. Move on to your upper legs and repeat.

    • Continue these exercises for your hands and lower arms, upper arms and shoulders, and finally your stomach and abdominal muscles. Repeat daily.[23]

  3. Take a mental vacation. The APA also suggests that, no matter where you are and even if you can’t go on an actual vacation, you can take a mental vacation. Take a few deep breaths, relax, and close your eyes. Imagine the most beautiful place you have ever been or your dream vacation spot.

    • Try to experience that place as fully as you can, smelling the smells, feeling a breeze, hearing the sounds. Repeat daily.[24]

  4. 4

    Try emergency stress relievers. The American Heart Association (AHA) recommends certain emergency stress relievers. They suggest that, if you find yourself under too much stress, count to 10 before you speak, take 3-5 deep breaths, walk away from the stressful situation, and say you’ll handle it later. You can also try going for a walk to clear your head.

    • To reduce stress, don’t be afraid to say “I’m sorry” if you make a mistake.
    • Avoid stressful situation by setting your watch 5-10 minutes ahead to avoid the stress of being late, driving in the slow lane, and avoiding busy roads to help you stay calm while driving.
    • Break down big problems into smaller parts. For example, answer one letter or phone call per day, instead of dealing with everything at once.[25]
  5. Practice good sleep hygiene. Your sleep hygiene is your daily routine of sleep related activities and your sleeping patterns. The National Sleep Foundation (NSF) recommends that you avoid naps during the day because naps tend to disturb the normal cycle of sleep and wakefulness. Also avoid stimulants, which include caffeine, nicotine, and alcohol, too close to bedtime. Alcohol can help you get to sleep, but can disrupt sleep later on as the body begins to metabolize the alcohol.

    • Only do vigorous exercise in the morning or late afternoon. Try more relaxing exercises, like stretching or yoga, later at night to help get a full night’s sleep.
    • Avoid large meals, chocolate, and spicy foods around bedtime.
    • Make sure you get exposure to natural sunlight. Light exposure helps maintain a healthy sleep-wake cycle.[26]

  6. Establish a relaxing bedtime routine. Try to avoid any emotional, physical, or mental upset before trying to go to sleep. Try not to dwell on problems in bed. If you find yourself reviewing the day or reviewing problems you have, try getting up again for 10-15 minutes.

    • During this time, do something that relaxes you like reading a book, doing deep breathing exercises, or meditating. Then, try going back to bed.
    • Associate your bed with sleep. Don’t use the bed to watch TV, listen to the radio, or read. If you link your bed with activities, your body will not want to sleep while in it.[27]

  7. Seek medical attention if necessary. If you have faithfully tried the lifestyle modifications and the natural remedies recommended and still have no relief after about 2-3 weeks, call your physician. You may need more direct medical help.

    • If you are pregnant or nursing, call your physician for advice on dealing with hyperacidity. Don’t try any of these approaches without discussing it with your physician first.
    • If you are taking medications and believe that your hyperacidity may be caused by these medications, call your physician and see if the medications or dose can be changed.

Taking Over the Counter Medication to Help Acid Reflux, monitor and see your doctor regularly

Understanding Acid Reflux

  1. Recognize the symptoms. Acid reflux can be quite common. Typical symptoms of acid reflux include heartburn, or a burning sensation in the chest. This can occur after eating or while you sleep. You may also experience a sour taste in the mouth, bloating, dark or black stools, burping or hiccups that won’t stop, nausea, dry coughs, or pain that gets worse when you bend over or lie down.

    • You may also experience dysphagia, which is a narrowed esophagus that feels as if there is food stuck in your throat.[33]

  2. Learn the triggers. There are a number of possible triggers for acid reflux. These triggers include smoking, overeating, stress, and lack of adequate sleep. It can be triggered by certain foods and beverages that you may be sensitive to, such as citrus fruit, caffeinated beverages, chocolate, tomatoes, garlic, onions, alcohol, fatty foods, and spicy foods.

    • Certain medications including aspirin, NSAIDs, muscle relaxants, and blood pressure medications can make acid reflux worse. Also, antibiotics, tetracycline, bisphosphonates, and some iron and potassium supplements can be a problem and make acid reflux worse.[34]

  3. Understand the causes. The actual cause of acid reflux is complicated and often includes many different causes. The cause, despite its name, is not the production of too much acid. Factors that can contribute to acid reflux are pressure on your stomach or esophagus. This can be caused by pregnancy, constipation, being overweight or obese, or a hiatal hernias, which is when the upper part of the stomach moves above the diaphragm.

    • It can also be caused by LES abnormalities, abnormal contractions in the esophagus, and slowed or prolonged emptying of the stomach.[35]

When Should You Try This?

  1. Use herbal remedies as an adult with acid reflux. Most natural acid reflux remedies are safe for the majority of adults. Note that some herbal remedies, however, may not be safe for children or teenagers. It’s best to try mild lifestyle changes first if you need to treat acid reflux in an adolescent. If these do not work, consult your doctor or do some thorough research before giving an adolescent an herbal remedy.

    • For example, you should not give aloe juice to children under the age of 12 since it typically results in abdominal pain, diarrhea, and cramping.[37]

  2. 2

    Try natural remedies in moderation. Most herbal remedies and other natural treatments will be safe in moderate amounts, but too much of a good thing can quickly become bad. When using herbal supplements, check the label for dosing instructions. For any natural remedy that does not have dosage instructions readily available, do some research to find out how much you should safely be able to endure.

    • For instance, aloe juice can cause stomach pain and other forms of digestive upset, especially if the juice contains aloe latex. Long-term use of large amounts can also result in kidney problems, muscle weakness, and heart problems. Make sure that any juice you drink contains no more than 200 mg aloe or 50 mg aloe latex to avoid complications.[38]
    • Consuming apple cider vinegar is usually considered safe short-term, but drinking 8 oz (250 ml) per day for several weeks or months may result in low potassium.[39]
    • High or prolonged doses of licorice root can result in headaches, fatigue, high blood pressure, heart attacks, and water retention. Do not take licorice for more than four to six weeks.[40]
  3. Consider natural remedies if you’re not pregnant or breastfeeding. If you are not currently pregnant or are not at risk of becoming pregnant, most natural remedies are likely safe for you. However, for acid reflux connected to pregnancy, always talk to your doctor before treating your symptoms to make sure you do not inadvertently harm your baby. It’s important that you do this before trying any herbal remedy, dietary fix, or lifestyle change.

    • Similarly, if you are currently breastfeeding, you may need to stay away from certain ingested remedies since they could get into your breastmilk and harm your baby. Most lifestyle remedies will likely be safe, though.
    • Potentially problematic remedies for pregnant and breastfeeding women include, but are not limited to, aloe juice, apple cider vinegar, ginger, fennel, licorice, and slippery elm.[41]

  4. Exercise caution if you have other medical conditions. In addition to pregnancy, certain medical conditions may also make herbal remedies or other natural fixes unsafe. If you have a known health concern other than acid reflux, talk to your doctor or do your research before trying any particular home cure.

    • Avoid aloe juice if you have diabetes, intestinal conditions, hemorrhoids, or kidney problems.[42]
    • Avoid apple cider vinegar if you have diabetes.[43]
    • Ginger may cause problems if you have a bleeding disorder, a heart condition, or diabetes.[44]
    • If you are allergic to celery, carrot, or mugwort, you may have an allergic reaction to fennel. You should also avoid fennel if you have a bleeding disorder or hormone-sensitive condition, like estrogen-sensitive cancers.[45]
    • Licorice root may cause problems if you have heart disease, heart failure, hormone-sensitive cancers, fluid retention, hypertension, diabetes, kidney disease, liver disease, or low potassium.[46]
    • If you have an immune system disorder, you may need to avoid taking probiotic supplements.[47]
    • Additionally, you may need to consult your doctor or avoid herbal remedies if you take certain medications, including medications for congestive heart failure, insulin, anti-diabetes drugs, stimulant laxatives, blood pressure medication, diuretic drugs, anticoagulant drugs, antiplatelet drugs, birth control pills, antibiotics, or estrogen pills.
  5. Treat your acid reflux after talking with your doctor. While most healthy adults can safely treat acid reflux at home using natural remedies, it’s never a bad idea to confirm the diagnosis with your doctor and discuss treatment options before making any major changes. This is especially important if you’ve already been trying home treatments and they haven’t worked.

    • If your condition worsens after following natural remedies or does not improve after two to three weeks, you may need to make an appointment with your doctor.
    • If you experience acid reflux symptoms more than twice per week or if you are unable to swallow/eat because of your symptoms, call your doctor before trying home remedies.
    • In addition to guiding your treatment and possibly prescribing stronger medications to treat your acid reflux, your doctor can verify that acid reflux is the problem and rule out other conditions that may behave in similar ways.

Ketosis: anti-brain fog, neurotransmitters, dietary protein, and the gut microbiome

Ketosis: anti-brain fog, neurotransmitters, dietary protein, and the gut microbiome

Treatment for dietary protein-induced brain fog: dark chocolate with 3% GOS and 10% MCTs.  Who’s in?

#IntermediaryMetabolism (bear with me here)
Ketosis from liver’s perspective:  increased fatty acid influx & [partial] oxidation causes acetyl-CoA levels to rise dramatically.  Concomitantly, gluconeogenesis redirects oxaloacetate (OAA) away from combining with acetyl-CoA via TCA cycle citrate synthesis and toward gluconeogenesis.  Since the acetyl-CoA doesn’t have much OAA with which to couple, it does itself to make acetoacetate.  Ergo, ketosis, and fortunately liver lacks ketolytic apparatus.

ketosis

Brain is singing a different tune.  Ketones provide ample acetyl-CoA and are efficiently metabolized in the TCA cycle.  Ketolysis is not ketogenesis in reverse, else liver would consume ketones.keto metabolism

Teleologically speaking (and I don’t really know what that word means), ketones are meant to spare glucose for the brain by replacing glucose as a fuel for peripheral tissues like skeletal muscle and displacing some brain glucose utilization.  The former is vital as one of the few sources of “new” glucose is skeletal muscle amino acids, and they would be exhausted in a short amount of time if skeletal muscle kept burning glucose –> incompatible with survival.  Getting some of that fuel from fatty acids, ie, ketones, is just way better.  Thus, the “glucose sparing effect of fat-derived fuel.”  And by “glucose,” I mean “muscle;” and by “fat-derived fuel,” I mean “ketones.”  There are numerous intracellular signaling events and biochemical pathways pwned, but that’s the gist of it.

Running brain on ketones considerably impacts amino acid metabolism, or more specifically neurotransmitters.  Ketogenic diets –> neuroprotective and improve cognitive functionimprove behavior in epileptic children, and even efficacious in bipolar disorder.  Many of these effects could be attributable to alterations in glutamate and gaba signaling.  Excitotoxicity.  brain fog.

Glutamate and gaba are two of the most quantitatively important neurotransmitters.  Glutamate can come from a transamination reaction or glutamine via phosphate-activated glutaminase.  It’s an expensive enzyme; one in which a few miscalculations in the lab can literally waste thousands of  a few of your tax bucks (ie, the kind of stuff that could’ve theoretically happened here) (sorry).  As it goes, glutamine is deaminated to glutamate, which is transaminated to alpha-ketoglutarate (aKG) or decarboxylated to gaba.  Glutamine is a precursor for glutamate and consequentially, gaba.  Glutamatergic neurons convert glutamine into glutamate, and gabaergic neurons convert glutamine to glutamate then via GAD to gaba (both of which can be recycled back to glutamine in astrocytes).Glutamine gaba

In liver, OAA is siphoned off for gluconeogenesis making it unavailable to facilitate fatty acid oxidation which leads to ketogenesis.  In brain, OAA effectively combines with ketone-derived acetyl-CoA, making it unavailable for transamination with aspartate (OAA + glutamate –> aspartate + aKG).

This could lead to elevated levels of glutamate (bad; excitotoxicity), but during ketosis, brain glutamate metabolism is apparently biased toward glutamine synthetase and GAD instead (both good).

Glutamine synthetase (GS)  mops up excess ammonia, which is thought to be a cause of brain fog at moderate levels and encephalopathy at high levels.  GS also detoxifies excitotoxic glutamate.  And GAD produces the calming neurotransmitter gaba.brain fog

Why no stellar data showing dramatic changes in vivo?  Speculation: said changes would be small and restricted to specific brain regions.  Total levels of glutamate & gaba might not even be altered, just flux and secretion patterns which would be difficult to detect.  However, this hasn’t stopped some review articles from saying these changes occur unequivocally (eg, Ruskin 2012), so maybe I’m wrong.  I’m still not going to bother trying to find studies where they dunk poor unsuspecting mouse into liquid nitrogen to prevent stress or anesthesia-induced alterations in extracellular neurotransmitters.   They probably exist, but I’m basing these assumptions on #IntermediaryMetabolism.

I suspect ammonia & glutamate are rather important in the etiology of brain fog due to the high sensitivity of Jane Plain’s brain to ketosis and dietary protein.

Glutamate and gaba are two ways ketosis may impact brain fog, but dietary protein might do so by a different mechanism: ammonia.

Ketogenic diets don’t include many bifidogenic foods.  Subtle alterations like this can lead to big changes in the way food is metabolized – some bugs love protein but hate nitrogen, or at least get rid of it via urease which creates ammonia.  Too much of this  = brain fog.  Forgetfulness, confusion, irritability.  Insomnia.  Ketogenic diet-induced increase in brain glutamine synthetase could likely take care of some, but may not be enough if dietary protein is too high.  And it isn’t frank encephalopathy, but rather some form of “clouding of consciousness.”   Although perhaps not so coincidentally, one way of managing hepatic encephalopathy is the bifidogenic laxative lactulose.

What about brain fog, treatment?  Ketogenic low protein diet, just like Mrs. Spratt (certainly not her husband)… although we suspect her problems were caused by an inherited disorder in the urea cycle.  Galactooligosaccharides (GOS) would work here because they have a strong potential to reduce urease-producing microbes.  And in at least one study (Malaguarnera 2007), bifidobacteria plus inulin worked for brain fog, which they called “minimal hepatic encephalopathy” probably because “clouding of consciousness” sounds ridiculous

[to journal editors who don’t understand medical conditions at which you can’t throw a statin or PPI (the latter being far worse in this case)].

Given that finding, I’m confident GOS would work better for two reasons: 1) supplementing live bifidobacteria requires financially restrictive doses to have an impact; and 2) GOS is far more bifidogenic than both inulin and actual bifidobacteria-based probiotics.

HT Purposelessness –> “Melancholic microbes: a link between gut microbiota and depression?” <–

In sufferers of brain fog, the tolerable level of dietary protein might just be dependent on architecture of the gut microbiome and degree of ketonemia.  Zhang and colleagues showed a linear relationship between brain ketone usage and blood ketone levels, and higher ketone usage could enhance clearance of glutamate and ammonia (2013).

To this end, MCTs or coconut oil may even facilitate the tolerance of brain fog to more dietary protein.  Throw in some galactooligosaccharides and we just might be on to something… I’m thinking a dark chocolate product supplemented with 3% GOS & 10% MCTs.

Dark chocolate is an optimal vessel for prebiotics.

Those percentages are negotiable, but 100 grams would provide a dose of GOS that is well-tolerated and remarkably bifidogenic.  MCTs at 10% should be OK, but if you love too much of this delicious chocolate, then too much more could cause digestive problems.

Ketosis: anti-brain fog. Neurotransmitters, dietary protein, and the gut microbiome.