Tag Archives: oxidative stress

Aspartame, blood sugar levels, and oxidative stress in the brain! a Paleo, microbiome-based perspective

400 x 400 tsf gb

In the course of researching patient cases and working on my next book, I read a lot of research studies. Sometimes, I come across information that wasn’t really what I was looking for, but is fascinating!

I have several patients who have chronic Lyme disease (yes, there is such a thing, but that’s a different subject…) and neurologic problems from depression/anxiety to failing memory, movement disorders, and even seizures are often commonplace in this type of patient. I was looking up more information about how oxidative stress, one of the underlying processes that drives neurologic problem progression, affects the brain. Along the way, I came across this study about N-acetyl cysteine and Aspartame.

N-acetyl cysteine, or NAC, is a precursor to glutathione (a powerful antioxidant) and as such it is a great tool to help reduce oxidative stress. Aspartame, more commonly known as NutraSweet, is a very common artificial sweetener.

This research study (see link below) was published in the journal Neurochemical Research in 2014, looked at NAC being used to protect the brain from the effects of Aspartame. Now mind you, if you ask 50 random people if they think NutraSweet is safe, most will claim it is and offer you a tinfoil hat if you mention anything about Monsanto and conspiracy to push the product to market. However, that is actually now an accepted fact, as Monsanto purchased G.D. Searle in 1985-the very company that held the patent to aspartame. In 1980 the FDA had banned aspartame, because the Board of Inquiry found that it might cause brain tumors. The Searle chairman at the time vowed he would get it approved. The chairman would later become famous as the Secretary of Defense, Donald Rumsfeld. A new FDA commissioner was appointed, who added people to the FDA board, and personally voted to break a tie and make aspartame legal. He later became employed by a public relations firm contracted by Monsanto and GD Searle. This product is now used in over 6,000 products, including over 500 different drugs.

The study in the Journal of Neurochemical Research matter-of-factly states that “Long-term intake of aspartame at the acceptable daily dose causes oxidative stress in rodent brain mainly due to the dysregulation of glutathione homeostasis”. It goes on to explain that aspartame reduced several antioxidant levels that are critical to brain health. They did find that NAC was able to exert a protective effect on the brain when it had been exposed to aspartame’s toxic effects.

One more tidbit is revealed in the study: “However, N-acetylcysteine was unable to reduce serum glucose levels, which were increased as a result of aspartame administration.” Another study evaluated the microbiome’s metabolism of aspartame and found that the end product is a short chain fatty acid, propionate, which raises blood sugar and reduces insulin sensitivity. In case that didn’t make sense to you, it makes blood sugar go up and insulin not work as well-building blocks of Type 2 diabetes. Isn’t the whole reason that people choose an artificial sweetener the idea that it won’t raise blood glucose like real carbohydrates would? Looks like it doesn’t really work that way! Now ask yourself why this isn’t more common knowledge…

In case you were wondering, that isn’t the only study that shows toxic effects of NutraSweet. Others have shown elevated cytokine levels (inflammation), as well as harmful/imbalancing effects on the gut microbiome.

Sometimes it is best to go back to what the body evolved and optimized to consume as food. The key word there is food, not chemistry! While many people are attempting to be on low-carb and Paleo diets to promote weight loss and health, the use of artificial sweeteners is definitely not a good addition to these diets. Some diets, such as South Beach, are actually recommending the full-fledged replacement of all simple carbs with artificial sweeteners. Many diabetics, the very people who need more insulin sensitivity and better glucose control, rely on very large doses of artificial sweeteners that are far above what is used in studies. For those pursuing a more traditional approach, the facts are even more clear. Consider that Paleo is supposed to mean Paleolithic; cave-dweller or hunter-gatherer. For 99+ percent of human existence, we’ve eaten meat, fish, vegetables, fruit, nuts-essentially whatever could be picked, dug up, gathered, or killed in the region and season being occupied. I’m pretty certain that didn’t include Monsanto’s chemical cocktails.

References:

Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach.

Alkafafy Mel-S, Ibrahim ZS, Ahmed MM, El-Shazly SA.

Int J Immunopathol Pharmacol. 2015 Jun;28(2):247-55. doi: 10.1177/0394632015586134. Epub 2015 May 26.

PMID:26015492

Longer period of oral administration of aspartame on cytokine response in Wistar albino rats.

Choudhary AK, Sheela Devi R.

Endocrinol Nutr. 2015 Mar;62(3):114-22. doi: 10.1016/j.endonu.2014.11.004. Epub 2015 Feb 11.

PMID:25681123

Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat.

Palmnäs MS, Cowan TE, Bomhof MR, Su J, Reimer RA, Vogel HJ, Hittel DS, Shearer J.

PLoS One. 2014 Oct 14;9(10):e109841. doi: 10.1371/journal.pone.0109841. eCollection 2014.

PMID:25313461

Free PMC Article

Artificial sweeteners induce glucose intolerance by altering the gut microbiota.

Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, Israeli D, Zmora N, Gilad S, Weinberger A, Kuperman Y, Harmelin A, Kolodkin-Gal I, Shapiro H, Halpern Z, Segal E, Elinav E.

Nature. 2014 Oct 9;514(7521):181-6. doi: 10.1038/nature13793. Epub 2014 Sep 17.

PMID:25231862

The carcinogenic effects of aspartame: The urgent need for regulatory re-evaluation.

Soffritti M, Padovani M, Tibaldi E, Falcioni L, Manservisi F, Belpoggi F.

Am J Ind Med. 2014 Apr;57(4):383-97. doi: 10.1002/ajim.22296. Epub 2014 Jan 16. Review.

PMID:24436139

Effect of aspartame on oxidative stress and monoamine neurotransmitter levels in lipopolysaccharide-treated mice.

Abdel-Salam OM, Salem NA, Hussein JS.

Neurotox Res. 2012 Apr;21(3):245-55. doi: 10.1007/s12640-011-9264-9. Epub 2011 Aug 6.

PMID:21822758

Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice.

Soffritti M, Belpoggi F, Manservigi M, Tibaldi E, Lauriola M, Falcioni L, Bua L.

Am J Ind Med. 2010 Dec;53(12):1197-206. doi: 10.1002/ajim.20896.

PMID:20886530

Aspartame and incidence of brain malignancies.

Davis DL, Ganter L, Weinkle J.

Cancer Epidemiol Biomarkers Prev. 2008 May;17(5):1295-6. doi: 10.1158/1055-9965.EPI-07-2869. No abstract available.

PMID:18483354

Free Article

Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats.

Soffritti M, Belpoggi F, Tibaldi E, Esposti DD, Lauriola M.

Environ Health Perspect. 2007 Sep;115(9):1293-7.

PMID:17805418

Free PMC Article

ADHD and the Microbiome: Any useful connections?

ADHD

Life sometimes keeps us quite busy, doesn’t it? I apologize to you, my readers, for the scarce blog posts. I’ve been in the process of pulling off an epic home move of about 1700 miles! So, I write this post while in a campground in Lamoine, Maine USA where I’ve been hunting up a new home for my family and I.

I did quite a bit of research reading about ADHD recently, and thought I would share a few thoughts about it.  Most of these thoughts are summarized in the flow chart drawing I created; refer to it when reading this blog post and you’ll see what I mean. What can be learned from a simple uBiome stool sample that can help with ADHD? Well, it turns out that there is quite a bit to look at there! As usual, this isn’t meant to replace your physician’s advice, and it is an example-which may not exactly describe your situation. You should consider using uBiome to run your (or your child’s) sample to see what your particular situation consists of.

The first thing to consider is the imbalance that frequently occurs in a microbiome. You see, it isn’t just about how many species of bacteria live in your gut, it is also about the relative numbers of those species. uBiome, after processing your sample, shows this in the simplest way by clicking on Taxonomy tree. In this format, the larger circles indicate larger populations while the smaller ones indicate, well, smaller. Clicking on each allows one to expand the data down from the phylum level all the way down to the genus level (remember, all life is cataloged by Kingdom, Phylum, Class, Order, Family, Genus, Species. We usually use Genus, Species to identify organisms, such as Homo sapiens or Helicobacter pylori.) When expanding these circles, often there is an obvious imbalance. At this point, I’m going to share some very specific information, and some or all of it may not apply to you or your child. It is an example of how a uBiome analysis can correlate with a condition and symptoms, directing some interventions. One recent patient case was a good example; the only large circles were Firmicutes, which is not such a bad thing. Opening that led to Clostridia being dominant, while Bacilli was minimal. This is meaningful because Bacilli includes Lactobacillus-one of the definite “good guys” that keep things working well. The phylum Actinobacteria was also minimal, significant because it includes another desirable genus, Bifidobacterium. This organism is an initial colonizer of the gut, tames the immune system, and also works with Lactobacillus to produce BDNF.

BDNF stands for Brain Derived Neurotrophic Factor, and it is necessary for the brain to develop new connections and grow/adapt to the life an individual leads. It is needed for plasticity, that ability of the brain to learn and adapt as needed. Low levels of BDNF are associated with ADHD. Your microbiome helps your brain to produce BDNF. Remember that a big part of what your brain learns to do as you grow up is actually blocking things out, not paying attention to more of them. It is a learning process, and in order to concentrate to accomplish tasks we must learn to attenuate non-essential information. This is also necessary for the brain to conserve fuel, because having a neural response to every incoming signal would burn a lot of fuel-in fact, enough to run out in some areas and cause Oxidative Stress.

Oxidative stress can result from depressed levels of antioxidant reserves or from too much stimulation. When nerve cells get overstimulated, they build up waste products and the energy-producing mitochondria become damaged. This is a “cellular death spiral”, because as soon as the mitochondria become damaged, the cell’s capability to metabolize fuel and produce energy is compromised, leading to more oxidative stress and further damage. This has been identified as part of the disease process in Alzheimer’s and Parkinson’s as well as ADHD and Autism. One of the problems that can promote Oxidative Stress is Inflammation.

Inflammation occurs when the immune system become too reactive and begins to attack tissue that is “self” and not “intruder/enemy”. Bifidobacteria are known for helping to dampen the immune inflammatory response, and a deficiency of Bifido contributes to inflammation. Again, inflammation is a key building block of…yes, all the same neurologic diseases. Low levels of Bifidobacteria and Lactobacillus are also significant because these organisms produce a neurotransmitter called Gamma Amino Butyric Acid or GABA.

GABA is an inhibitory neurotransmitter in the brain, and calming drugs or herbs often boost GABA levels. Valerian root or Valium (copycat drug companies, you know?) are good examples as is Kava Kava. Low levels of Lacto and Bifido gut bacteria result in low levels of GABA at the brain. Low levels of GABA at the brain result in less inhibition…ergo, more stimulation! And, the process continues in a positive feedback loop.

It is interesting to note that one intervention that helps elevate GABA and BDNF is exercise. Kids with ADHD are known for often being hyperkinetic, so if you wondered why, it is their brain’s way of balancing the equation to save nerve cells! When kids are reprimanded by teachers and parents are shamed into medicating their children’s “high energy”, it can be detrimental to the developmental process for this reason. This doesn’t mean that doing nothing is better, as a child must be able to focus in order to be able to learn. It just means that medicating their energy level down does not address the root causes of the problem.

So, what would be some natural interventions? First, improved nutrition. Any food that is causing more inflammation needs to be removed from the diet. Often that is sweets (note that Clostridia like sweets) and sometimes specific items such as gluten containing foods. Adding probiotics that contain the Lacto and Bifido organisms (in this patient example) can of course be helpful, but more so if they are also fed the prebiotic fibers that they need to survive (again, ideally this is case-specific). Both can be added to a fruit and vegetable smoothie that is tasty. Neuroprotective supplements such as N-Acetylcysteine will help to minimize the neuronal damage that is occurring. Also DHA/Omega-3 oils are neuroprotective and have been shown to help with ADHD. Curcumin can also reduce the neuroinflammation and is protective as well. It can also help settle gut function and heal the membranes of the intestines if they were inflamed too. Eating less processed food and more fresh (organic as possible) fruits and vegetables helps.

All of these steps are best carried out after having a stool sample analyzed for gut bacteria. Only after seeing the “bacterial census” is it possible to be extremely specific. A different patient’s samples could result in different recommendations! Please contact me for more details should you wish to find out more or schedule an analysis. This does not have to be done locally, as I only need the data from uBiome and a patient questionnaire to determine recommendations. Some of the supplements recommended are not case-specific, such as NAC, DHA/Omega and Curcumin as these will help most types of situations as will a healthier diet. The probiotic formulation is ideally case-specific, as is the prebiotic fibers and these will preferentially feed some categories of organisms more than others.

With proper lab work and specific interventions, it is possible for many individuals with ADHD to control and manage their situation more effectively. For some, it will be more of a cure, with no medication needed. For others, it may mean less medication is needed or the medication works more effectively. It is important to realize that we are all different, and our situations are also different!

Sources for supplements: http://progressivelabs.com/   You’ll have to register to order from them, and it requires specifying who referred you. Please feel free to put my name on that line, and then you will be able to receive your supplements directly from the same manufacturer I use!

References:

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Microb Ecol Health Dis. 2015 May 29;26:28177. doi: 10.3402/mehd.v26.28177. eCollection 2015.

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Deepmala, Slattery J, Kumar N, Delhey L, Berk M, Dean O, Spielholz C, Frye R.

Neurosci Biobehav Rev. 2015 Aug;55:294-321. doi: 10.1016/j.neubiorev.2015.04.015. Epub 2015 May 6. Review.

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Frye RE, Rose S, Slattery J, MacFabe DF.

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Physiol Behav. 2015 Aug 1;147:78-83. doi: 10.1016/j.physbeh.2015.04.012. Epub 2015 Apr 11.

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Behav Brain Funct. 2014 Nov 25;10:43. doi: 10.1186/1744-9081-10-43.

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Why Diet and Gut Bacterial Symbionts may be the most important thing you learn about Autism Spectrum Disorder

Autism is a neurobehavioral condition that has been dramatically on the rise in the last decade. There are many factors that contribute to its causes, but none so pervasive as gut bacterial imbalance. To see the connections, you first have to realize that our brain development is heavily influenced by the interaction between our gut bacterial symbionts, our immune system, and those little cell organelles that produce energy-known as mitochondria. I explained at length how the gut bacteria influence brain development in The Symbiont Factor; in short there are many pathways for influence including gut bacterial alteration of Brain Derived Neurotrophic Factor or BDNF. This substance is necessary for proper nerve growth and development, and a deficiency or imbalance in gut bacteria results in a reduced level of BDNF. New research has shown another factor in brain development, Short Chain Fatty Acids or SCFA. This substance is produced by bacterial fermentation of carbohydrates (sweets, essentially!)  Eating too many carbohydrates results in increased populations of the gut bacteria that thrive on sugars, including Clostrida, desulfovibrio, and Bacteroides. When these bacteria ferment carbs, they produce high levels of SCFA including propionic acid which is one SCFA. Propionic acid is also a common food preservative in prepared foods, so read your ingredients and eat organic as much as possible. New research has shown that high propionic acid levels interfere with mitochondrial function, reducing the energy available for nerve cell function and producing ASD. It is important to understand that some of the organisms that produce propionic acid are not necessarily pathogens; more like “frenemies” in this case (see Jerry Seinfeld; friend + enemy, and a good laugh too) Establishing and maintaining a microbial balance is really a more accurate way to state the goal. The overuse of vaccines and antibiotics in children, combined with chemicals in packaged food and toxins in farm-raised food are all factors that conspire to imbalance our gut bacteria. It is worth noting that reduced mitochondrial function also results in elevated oxidative stress, which is the neuroinflammatory/degenerative process that drives many diseases from fibromyalgia or chronic fatigue syndrome to Parkinson’s, dementia, and aging in general. Significant variables that we can influence include diet (less sweets, more organic fruits and veggies and organic grassfed meat; organic Paleo diet essentially) and behavior. Pushing ourselves past the point of fatigue, or allowing small children to stay “in overdrive” too long with video games and sweets, causes more bacterial imbalance and neurologic dysfunction. Many supplements, from Curcumin and probiotics with Lactobacillus and Bifido species, to fermented foods and drinks such as GoodBelly and Lifeway Kefir, can help to build and maintain healthy levels of gut bacteria and give our kids the best chance possible of good health and function. The next time a stranger at the bank drive through offers your child “a sucker”, consider the potential effects of regular sugar ingestion on a child’s microbiome and brain function. Really!

For much more about the role of diet and gut symbiont bacteria on brain development, behavior and health, please check out my book The Symbiont Factor: http://tinyurl.com/qyg85t9

References:

http://www.ncbi.nlm.nih.gov/pubmed/26031685

http://www.ncbi.nlm.nih.gov/pubmed/24466331

http://www.ncbi.nlm.nih.gov/pubmed/26046240

http://www.ncbi.nlm.nih.gov/pubmed/25956238

http://www.ncbi.nlm.nih.gov/pubmed/25956237

http://www.ncbi.nlm.nih.gov/pubmed/25852770

http://www.ncbi.nlm.nih.gov/pubmed/25911232

http://www.ncbi.nlm.nih.gov/pubmed/25852213