Author Archives: Dr. Richard Matthews

When that chemical you avoid, is food to your good gut bacteria…

chinese-take-outHere’s some quick food for thought: isn’t it funny that we consider MSG a bad thing (due to it being monosodium glutamate, and glutamate is an excitatory neurotransmitter), and many people have problems with it-yet the two most beneficial gut symbionts we know of actually consume MSG and metabolize it into GABA, which is the brain neurotransmitter that is calming and inhibitory…almost like MSG sensitivity could be a marker for poor levels of Lactobacillus and Bifidobacteria, isn’t it? And, people sensitive to MSG often have problems with excitotoxicity, where the brain is overstimulated by the MSG. Almost like? yes, not enough inhibitory GABA. hmmm.

https://www.ncbi.nlm.nih.gov/pubmed/22612585

Cancer researchers identify need for this…

It appears that the microbiome’s ability to help fight cancer is being recognized. This study identifies weaknesses in current cancer care protocols, pointing out that chemotherapy and antibiotics diminish the microbiome, and that the microbiome increases immune response to cancer cells. So, really, part of cancer care should be building up the microbiome. Just an example of one of those times that the most advanced science proved the need for ancient practices 🙂 https://www.ncbi.nlm.nih.gov/pubmed/24832470

BCAA Branched Chain Amino Acids and how they boost Bifidobacterium and Akkermansia

Branched Chain Amino Acids, BCAA’s, are a common addition to the diet for bodybuilders and athletes. Here’s a new research study, published this month, that shows BCAA’s help change your gut bacteria. Specifically, the encourage more Bifidobacteria (which boosts immune function but lowers inflammation) and Akkermansia (which helps build lean muscle mass and reduce fat). As there is much research now connecting aging with inflammation, even calling it “inflammaging”, these are both great things. It’s also somewhat of a departure from the thought of usng probiotics and prebiotics to modulate the gut bacteria, adding amino acids to our microbiome toolbox!

http://www.ncbi.nlm.nih.gov/pubmed/27539648

Parkinson’s Disease, Inflammation and Oxidative Stress: Natural Help

??????????????????????????????????????????????????????????????????????

Most of us should be familiar with the disease known as Parkinson’s Disease, which ruins countless lives by creating a movement disorder characterized by shaking type of movements. It leads to difficulty moving at all, and in late stages the most common treatments lead to dyskinesthia which is a type of writhing uncontrolled movement. Without detailing the actual nerve pathways, part of the problem is neurodegeneration in a part of the brain called the basal ganglia, in an area known as the Substantia Nigra. When this area is overtaxed and inflamed, a process known as oxidative stress occurs, damaging neurons and created neurofibrous “tangles” known as α-synuclein aggregations.

There is a great deal of research that has been done to detail some natural ingredients that can be used to either prevent, or help treat Parkinson’s. These can sometimes reduce the amount of medication needed, and postpone the onset of dyskinesthia. In some cases successful treatment has occurred and symptoms are gone. The major “theme” of treatment with natural products is to reduce inflammation, block oxidative stress, and promote healthy metabolism in those neuronal cells.

Curcumin is an extract of turmeric, and contains 95% curcuminoids-the active ingredient. This makes it 19 times stronger than turmeric, which only contains 5%. Curcumin has been found to block inflammation, reduce oxidative stress, rescue nerve cells that have been affected, and even to reverse the accumulation of α-synuclein in the brain. I’ve attached a little over two dozen peer-reviewed studies about curcumin and Parkinson’s in the Bibliography. Curcumin is best taken before a meal, and with a tablespoon of coconut oil which boosts absorption and is good for the brain as well.

Another useful herb is Skullcap, Scuttelaria baikalensis, which contains the ingredient Baicalein. This has also been extensively studied for use in treating and reversing some of the effects of Parkinson’s, and is a very promising herb. Note that there aren’t any studies that look at what would happen if you use this AND curcumin, but you can imagine that it should work even better as they do not function through the same mechanisms.

The last strategy I’d like to mention is gut bacteria optimization. As I wrote an entire book about gut bacteria (The Symbiont Factor) I’ll try to be brief. Our gut bacteria wield a big influence on brain and immune function, helping to both tone and control immune function and regulate both the production of neurotransmitters and the sensitivity of neurotransmitter receptor sites in the brain. An imbalance of gut bacteria, which can be assessed with a uBiome.com gut bacteria census, can create functional changes that make the brain less efficient and more inflamed. This sets the stage for Parkinson’s, as neuroinflammation is a required building block of this disease.

Now, you might ask yourselves why this information is not more well known in the Parkinson’s world…it doesn’t actually even appear on the National Parkinson’s Foundation website although many less effective interventions are mentioned. This is because, simply, much of the research is done in search of new drugs to create by copying the action of useful herbs and natural processes. This is one way that companies explore for new drugs that can be patented. The real question is why we would wait for that, when the research shows these natural substances to be quite effective in lab and animal models. Of course, double-blind trials on humans will not be performed until drug candidates are created…so don’t look for the final proof of natural substances, because these trials are very expensive and are only carried out when a candidate drug ($$$) is being evaluated. In other words, follow the money!

Bibliography:

The Symbiont Factor: http://tinyurl.com/z5568ct

Baicalein inhibits α-synuclein oligomer formation and prevents progression of α-synuclein accumulation in a rotenone mouse model of Parkinson’s disease.

Hu Q, Uversky VN, Huang M, Kang H, Xu F, Liu X, Lian L, Liang Q, Jiang H, Liu A, Zhang C, Zhu S.

Biochim Biophys Acta. 2016 Jul 14. pii: S0925-4439(16)30168-5. doi: 10.1016/j.bbadis.2016.07.008. [Epub ahead of print]

PMID:27425033

Ameliorative effects of baicalein in MPTP-induced mouse model of Parkinson’s disease: A microarray study.

Gao L, Li C, Yang RY, Lian WW, Fang JS, Pang XC, Qin XM, Liu AL, Du GH.

Pharmacol Biochem Behav. 2015 Jun;133:155-63. doi: 10.1016/j.pbb.2015.04.004. Epub 2015 Apr 18.

PMID:25895692

Baicalein ameliorated the upregulation of striatal glutamatergic transmission in the mice model of Parkinson’s disease.

Xue X, Liu H, Qi L, Li X, Guo C, Gong D, Qu H.

Brain Res Bull. 2014 Apr;103:54-9. doi: 10.1016/j.brainresbull.2014.02.004. Epub 2014 Feb 24.

PMID:24576689

Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving PKCα and PI3K/AKT signaling pathways.

Zhang Z, Cui W, Li G, Yuan S, Xu D, Hoi MP, Lin Z, Dou J, Han Y, Lee SM.

J Agric Food Chem. 2012 Aug 22;60(33):8171-82. doi: 10.1021/jf301511m. Epub 2012 Aug 9.

PMID:22838648

[Neuroprotective effect of baicalein in patients with Parkinson’s disease].

Yu X, He G, Du G.

Zhongguo Zhong Yao Za Zhi. 2012 Feb;37(4):421-5. Review. Chinese.

PMID:22667137

Assessment of the treatment effect of baicalein on a model of Parkinsonian tremor and elucidation of the mechanism.

Yu X, He GR, Sun L, Lan X, Shi LL, Xuan ZH, Du GH.

Life Sci. 2012 Jul 26;91(1-2):5-13. doi: 10.1016/j.lfs.2012.05.005. Epub 2012 May 23.

PMID:22634324

Baicalein inhibits formation of α-synuclein oligomers within living cells and prevents Aβ peptide fibrillation and oligomerisation.

Lu JH, Ardah MT, Durairajan SS, Liu LF, Xie LX, Fong WF, Hasan MY, Huang JD, El-Agnaf OM, Li M.

Chembiochem. 2011 Mar 7;12(4):615-24. doi: 10.1002/cbic.201000604. Epub 2011 Jan 26.

PMID:21271629

Flavones from root of Scutellaria baicalensis Georgi: drugs of the future in neurodegeneration?

Gasiorowski K, Lamer-Zarawska E, Leszek J, Parvathaneni K, Yendluri BB, Błach-Olszewska Z, Aliev G.

CNS Neurol Disord Drug Targets. 2011 Mar;10(2):184-91. Review.

PMID:21222632

Structural characteristics of alpha-synuclein oligomers stabilized by the flavonoid baicalein.

Hong DP, Fink AL, Uversky VN.

J Mol Biol. 2008 Oct 31;383(1):214-23. doi: 10.1016/j.jmb.2008.08.039. Epub 2008 Aug 23.

PMID:18775438

Free PMC Article

The flavonoid baicalein inhibits fibrillation of alpha-synuclein and disaggregates existing fibrils.

Zhu M, Rajamani S, Kaylor J, Han S, Zhou F, Fink AL.

J Biol Chem. 2004 Jun 25;279(26):26846-57. Epub 2004 Apr 19.

PMID:15096521

Free Article

 

Curcumin Rescues a PINK1 Knock Down SH-SY5Y Cellular Model of Parkinson’s Disease from Mitochondrial Dysfunction and Cell Death.

van der Merwe C, van Dyk HC, Engelbrecht L, van der Westhuizen FH, Kinnear C, Loos B, Bardien S.

Mol Neurobiol. 2016 Mar 22. [Epub ahead of print]

PMID:27003823

Curcumin improves neurofunctions of 6-OHDA-induced parkinsonian rats.

Song S, Nie Q, Li Z, Du G.

Pathol Res Pract. 2016 Apr;212(4):247-51. doi: 10.1016/j.prp.2015.11.012. Epub 2015 Nov 18.

PMID:26922613

Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway.

Cui Q, Li X, Zhu H.

Mol Med Rep. 2016 Feb;13(2):1381-8. doi: 10.3892/mmr.2015.4657. Epub 2015 Dec 8.

PMID:26648392

Curcumin inhibits apoptosis by regulating intracellular calcium release, reactive oxygen species and mitochondrial depolarization levels in SH-SY5Y neuronal cells.

Uğuz AC, Öz A, Nazıroğlu M.

J Recept Signal Transduct Res. 2016 Aug;36(4):395-401. doi: 10.3109/10799893.2015.1108337. Epub 2015 Nov 25.

PMID:26608462

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease models.

Ganesan P, Ko HM, Kim IS, Choi DK.

Int J Nanomedicine. 2015 Oct 29;10:6757-72. doi: 10.2147/IJN.S93918. eCollection 2015. Review.

PMID:26604750

Free PMC Article

Plant-derived neuroprotective agents in Parkinson’s disease.

Fu W, Zhuang W, Zhou S, Wang X.

Am J Transl Res. 2015 Jul 15;7(7):1189-202. eCollection 2015. Review.

PMID:26328004

Free PMC Article

Curcumin Treatment Improves Motor Behavior in α-Synuclein Transgenic Mice.

Spinelli KJ, Osterberg VR, Meshul CK, Soumyanath A, Unni VK.

PLoS One. 2015 Jun 2;10(6):e0128510. doi: 10.1371/journal.pone.0128510. eCollection 2015.

PMID:26035833

Free PMC Article

Relevance of the anti-inflammatory properties of curcumin in neurodegenerative diseases and depression.

Tizabi Y, Hurley LL, Qualls Z, Akinfiresoye L.

Molecules. 2014 Dec 12;19(12):20864-79. doi: 10.3390/molecules191220864. Review.

PMID:25514226

Free Article

Curcumin’s neuroprotective efficacy in Drosophila model of idiopathic Parkinson’s disease is phase specific: implication of its therapeutic effectiveness.

Phom L, Achumi B, Alone DP, Muralidhara, Yenisetti SC.

Rejuvenation Res. 2014 Dec;17(6):481-9. doi: 10.1089/rej.2014.1591.

PMID:25238331

Free PMC Article

The use of nanopore analysis for discovering drugs which bind to α-synuclein for treatment of Parkinson’s disease.

Tavassoly O, Kakish J, Nokhrin S, Dmitriev O, Lee JS.

Eur J Med Chem. 2014 Dec 17;88:42-54. doi: 10.1016/j.ejmech.2014.07.090. Epub 2014 Jul 25.

PMID:25081642

Neuroprotective effect of curcumin on hippocampal injury in 6-OHDA-induced Parkinson’s disease rat.

Yang J, Song S, Li J, Liang T.

Pathol Res Pract. 2014 Jun;210(6):357-62. doi: 10.1016/j.prp.2014.02.005. Epub 2014 Feb 23.

PMID:24642369

Curcumin protects axons from degeneration in the setting of local neuroinflammation.

Tegenge MA, Rajbhandari L, Shrestha S, Mithal A, Hosmane S, Venkatesan A.

Exp Neurol. 2014 Mar;253:102-10. doi: 10.1016/j.expneurol.2013.12.016. Epub 2013 Dec 29.

PMID:24382451

Protective effects of curcumin against rotenone and salsolinol-induced toxicity: implications for Parkinson’s disease.

Qualls Z, Brown D, Ramlochansingh C, Hurley LL, Tizabi Y.

Neurotox Res. 2014 Jan;25(1):81-9.

PMID:24122264

Free PMC Article

The multiple pharmaceutical potential of curcumin in Parkinson’s disease.

Ji HF, Shen L.

CNS Neurol Disord Drug Targets. 2014 Mar;13(2):369-73. Review.

PMID:23844695

Curcumin modulates α-synuclein aggregation and toxicity.

Singh PK, Kotia V, Ghosh D, Mohite GM, Kumar A, Maji SK.

ACS Chem Neurosci. 2013 Mar 20;4(3):393-407. doi: 10.1021/cn3001203. Epub 2012 Dec 17.

PMID:23509976

Free PMC Article

Curcumin ameliorates the neurodegenerative pathology in A53T α-synuclein cell model of Parkinson’s disease through the downregulation of mTOR/p70S6K signaling and the recovery of macroautophagy.

Jiang TF, Zhang YJ, Zhou HY, Wang HM, Tian LP, Liu J, Ding JQ, Chen SD.

J Neuroimmune Pharmacol. 2013 Mar;8(1):356-69. doi: 10.1007/s11481-012-9431-7. Epub 2013 Jan 17.

PMID:23325107

Curcumin inhibition of JNKs prevents dopaminergic neuronal loss in a mouse model of Parkinson’s disease through suppressing mitochondria dysfunction.

Pan J, Li H, Ma JF, Tan YY, Xiao Q, Ding JQ, Chen SD.

Transl Neurodegener. 2012 Aug 20;1(1):16. doi: 10.1186/2047-9158-1-16.

PMID:23210631

Free PMC Article

Neurodegenerative Shielding by Curcumin and Its Derivatives on Brain Lesions Induced by 6-OHDA Model of Parkinson’s Disease in Albino Wistar Rats.

Agrawal SS, Gullaiya S, Dubey V, Singh V, Kumar A, Nagar A, Tiwari P.

Cardiovasc Psychiatry Neurol. 2012;2012:942981. doi: 10.1155/2012/942981. Epub 2012 Aug

Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson’s disease.

Du XX, Xu HM, Jiang H, Song N, Wang J, Xie JX.

Neurosci Bull. 2012 Jun;28(3):253-8. doi: 10.1007/s12264-012-1238-2.

PMID:22622825

Neuroprotective effect of curcuminoids against inflammation-mediated dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease.

Ojha RP, Rastogi M, Devi BP, Agrawal A, Dubey GP.

J Neuroimmune Pharmacol. 2012 Sep;7(3):609-18. doi: 10.1007/s11481-012-9363-2. Epub 2012 Apr 21.

PMID:22527634

Curcumin has neuroprotection effect on homocysteine rat model of Parkinson.

Mansouri Z, Sabetkasaei M, Moradi F, Masoudnia F, Ataie A.

J Mol Neurosci. 2012 Jun;47(2):234-42. doi: 10.1007/s12031-012-9727-3. Epub 2012 Mar 15.

PMID:
22418789
 

Curcumin protects against A53T alpha-synuclein-induced toxicity in a PC12 inducible cell model for Parkinsonism.

Liu Z, Yu Y, Li X, Ross CA, Smith WW.

Pharmacol Res. 2011 May;63(5):439-44. doi: 10.1016/j.phrs.2011.01.004. Epub 2011 Jan 12.

PMID:21237271
 

Curcumin reduces alpha-synuclein induced cytotoxicity in Parkinson’s disease cell model.

Wang MS, Boddapati S, Emadi S, Sierks MR.

BMC Neurosci. 2010 Apr 30;11:57. doi: 10.1186/1471-2202-11-57.

PMID:20433710

Free PMC Article

About those “Turmeric Curcumin” capsules…

th (2)

I have been recommending curcumin for years, because of the huge number of research studies demonstrating its power to reduce inflammation, block oxidative stress, and inhibit or kill cancer (and other great benefits!) Lately there has been an explosion of supplements labeled as “turmeric curcumin” or “curcumin complex”. This is about like trying to buy pure cranberry juice. If you see “cranberry juice cocktail” or “cranberry drink” or “cranberry juice beverage”, what does it tell you? Right-it’s mostly apple juice or some other inexpensive juice, with enough of the cranberry juice to flavor it!

The same thing applies to curcumin. I have recommended it to several patients recently, who then tell me a couple weeks later that it didn’t help them. When I ask about the brand and details, it’s one of those labeling bait-and-switch schemes all over. Often the label reads “turmeric curcumin” which really doesn’t mean much, as they are two separate products…which is it? or “turmeric curcumin complex”…

The active, desired ingredient is Curcumin. Turmeric, the spice, is quite inexpensive but only contains typically 5% curcumin. Pure curcumin is most often 95% curcumin, and costs much much more. So, when the label explains that the product contains 450 mg of Turmeric, and 50 mg of curcumin, you can easily see that you’re getting basically ripped off because they’re cutting the good stuff 9:1 with the inexpensive less effective stuff! Then, of course, it doesn’t work as well, because you can’t take enough. I often recommend 6 capsules per day for a very inflamed patient (someone with Lyme disease, for example). That’s 6, 500mg capsules at 95%, or 2850 mg of actual curcumin. If those capsules are 450/50 as in the above example, that’s only 70mg of curcumin in each 500 mg capsule. To get the same effect as 2850 mg of pure curcumin, you’d have to consume over 40 of those capsules, instead of 6 when it’s 95% curcumin!

So, make sure that you get what you’re paying for-real 95% curcumin. There isn’t a “bioavailability problem” as some manufacturers of blends state. It’s a fat soluble substance, so chase your capsules with a spoon of coconut oil. It’s also alcohol soluble…well, I won’t go there just yet!

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

Stress, Microbiome, Inflammation and the Pancreas & Liver

flow chart stress intestinal function inflammation

Sometimes things happen that seem to come out of nowhere. It happens to all of us, usually when we least expect it because we are busy taking care of others or life in general. So here’s a scenario: Imagine that one day your blood sugar suddenly skyrockets and your Medical physician informs you that your liver and pancreas are not functioning properly. What could cause this? Well, many things could, but the one thing in common is inflammation. If the pancreas is inflamed, the Islets of Langerhans sometimes stop producing insulin and blood sugar doesn’t get stored, so it jumps up. If the inflammation is early in life, the immune system may go to the point of forming antibodies to the Islets, destroying them and causing Type 1 diabetes. If the body becomes inflamed later in life, cells may not respond to insulin anymore, causing Type 2 diabetes. But if the pancreas is inflamed, it doesn’t work properly. The liver can be implicated too, as it stores extra energy (glucose) reserves for when you need them. Liver inflammation can also cause diabetes. While these changes are all known to occur in people that are obese and have an unhealthy diet, how is it possible for it to happen this quickly, and in someone who isn’t obese? The answer lies in the fact that the immune system is mostly controlled by our gut bacteria and GALT, or gut-associated lymphoid tissue, dendritic nerve endings, and other points of information exchange between the microbiome and the host immune system.

Research has shown that exposure to short-term social/emotional stress causes alteration of the gut microbiome. This altered microbiome in turn does not control the immune system approriately, resulting in increased systemic inflammation (which can make the social stress worse, as both the inflammation and the altered microbiome affect brain function and mood). See the illustration above, which is from my book The Symbiont Factor.

Another factor that can alter the microbiome and trigger widespread inflammation is short term dietary change, to a less beneficial diet. In research terminology, a diet that causes microbiome demise, inflammation and disease is called a Western Diet. It is used to produce a sick lab animal to study, and mimics what the average American consumer eats every day.

Sleep is absolutely necessary for a healthy microbiome, and disruptions of our circadian rhythms and sleep cycles has been shown to disrupt our microbiome and cause inflammation.

Exposure to air affects our microbiome too! Air is actually replete will huge numbers of human skin cells and bacteria from other people in the vicinity. The longer we are in a space with other people, the more we inhale parts of their microbiome combined with the microbiome of the space. These organisms then influence our own microbiome, so if the exposure was to unhealthy microbiomes, the result can be…inflammation once more.

Sometimes the scenario can revive imbalances and infections we’ve had before, such as chronic viral infections (shingles, for example, or herpes) or chronic bacterial infections such as Lyme disease-where the organism was in a dormant state due to good immune function-waiting for an opportunity.

Ok, so…can we picture a scenario where all of the above are combined? Stress, bad food, interrupted sleep with no real dark/light cycles, and lots of sick people/bad bacteria? Bingo-it’s the place where we send people to get well: a hospital.

What should we do to recover from this systemic inflammation?

  1. Regular sleep, hitting the bed and waking same time every day, preferably in a multiple of 90 minutes. So, 6 hours, 7.5 hours, 9 hours so that we don’t interrupt a sleep cycle. No lights, no devices at night. No bright little blue “charging” LEDs.
  2. Healthy food, and preferably some of it fermented. There is a great fermented oatmeal recipe earlier on this blog, and many areas have private individuals making fantastic fermented vegetables. Here in coastal Maine, “A Stone’s Throw to Health” is one such business, with handcrafted ferments by Sheila Perloff-Eddison.
  3. Avoid deep fried food, hydrogenated fats, sweets, gluten. Even if you’re not gluten sensitive, eating it when you’re inflamed raises the odds of you becoming gluten sensitive. No fast food. Real meat, vegetable, greens, fruit.
  4. Probiotic Bifidobacteria, in double the normal doses. Add prebiotic inulin, pectin, FOS, GOS supplements to help feed the newly introduced organisms.
  5. Curcumin is hugely effective for reducing inflammation, improving insulin sensitivity, healing liver and pancreas. Not turmeric, which is 5% curcumin, but 95% curcumin-the real stuff. I take 6-8 capsules a day, minimum, if I’m injured or inflamed. It works better than drugs-check out the Ghosh study in the bibliography below.
  6. Some other products, such as jerusalem artichokes/sunchokes, jicama, artichokes, asparagus, pomegranate, rhubarb, ginger have been shown to have fantastic prebiotic and anti-inflammatory benefits.
  7. Make a point of, several times per day, praying or meditating on peaceful/optimistic and loving thoughts while breathing deeply. The physiologic effects improve autonomic tone and gut function, helping to recolonize healthy bacteria while healing gut membranes.

 

Sources:

Fermented Vegetables: http://www.astonesthrowtohealth.com/

Curcumin: http://progressivelabs.com/product.php?productid=17110&cat=0&page=1

Inulin: http://www.amazon.com/Prebiotin-Prebiotic-Fiber-8-5-Powder/dp/B001RVFSFS/ref=sr_1_2_a_it?ie=UTF8&qid=1459361720&sr=8-2&keywords=prebiotic

For more info: http://www.amazon.com/Symbiont-Factor-Microbiome-Redefines-Humanity/dp/1500553948/

Fermented oatmeal recipe: https://thesymbiontfactorblog.com/2016/01/26/super-synbiotic-breakfast-improved/

 

Bibliography:

Rhubarb extract prevents hepatic inflammation induced by acute alcohol intake, an effect related to the modulation of the gut microbiota.

Neyrinck AM, Etxeberria U, Taminiau B, Daube G, Van Hul M, Everard A, Cani PD, Bindels LB, Delzenne NM.

Mol Nutr Food Res. 2016 Mar 18. doi: 10.1002/mnfr.201500899. [Epub ahead of print]

PMID:26990039

Combination with Red ginseng and Polygoni Multiflori ameliorates highfructose diet induced metabolic syndrome.

Kho MC, Lee YJ, Park JH, Cha JD, Choi KM, Kang DG, Lee HS.

BMC Complement Altern Med. 2016 Mar 9;16(1):98. doi: 10.1186/s12906-016-1063-7.

PMID:26961224

Free PMC Article

Chronic Psychological Stress Disrupted the Composition of the Murine Colonic Microbiota and Accelerated a Murine Model of Inflammatory Bowel Disease.

Watanabe Y, Arase S, Nagaoka N, Kawai M, Matsumoto S.

PLoS One. 2016 Mar 7;11(3):e0150559. doi: 10.1371/journal.pone.0150559. eCollection 2016.

PMID:26950850

Free PMC Article

Early Alterations in Glycemic Control and Pancreatic Endocrine Function in Nondiabetic Patients With Chronic Pancreatitis.

Lundberg R, Beilman GJ, Dunn TB, Pruett TL, Freeman ML, Ptacek PE, Berry KL, Robertson RP, Moran A, Bellin MD.

Pancreas. 2016 Apr;45(4):565-71. doi: 10.1097/MPA.0000000000000491.

PMID:26918872

Hepatoprotective Effect and Synergism of Bisdemethoycurcumin against MCD Diet-Induced Nonalcoholic Fatty Liver Disease in Mice.

Kim SB, Kang OH, Lee YS, Han SH, Ahn YS, Cha SW, Seo YS, Kong R, Kwon DY.

PLoS One. 2016 Feb 16;11(2):e0147745. doi: 10.1371/journal.pone.0147745. eCollection 2016.

PMID:26881746

Free PMC Article

Protective Role of Dietary Curcumin in the Prevention of the Oxidative Stress Induced by Chronic Alcohol with respect to Hepatic Injury and Antiatherogenic Markers.

Varatharajalu R, Garige M, Leckey LC, Reyes-Gordillo K, Shah R, Lakshman MR.

Oxid Med Cell Longev. 2016;2016:5017460. doi: 10.1155/2016/5017460. Epub 2016 Jan 5.

PMID:26881029

Free PMC Article

Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

Yarla NS, Bishayee A, Sethi G, Reddanna P, Kalle AM, Dhananjaya BL, Dowluru KS, Chintala R, Duddukuri GR.

Semin Cancer Biol. 2016 Feb 4. pii: S1044-579X(16)30003-7. doi: 10.1016/j.semcancer.2016.02.001. [Epub ahead of print] Review.

PMID:26853158

Preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed obese rats.

Maithilikarpagaselvi N, Sridhar MG, Swaminathan RP, Sripradha R.

J Complement Integr Med. 2016 Feb 4. pii: /j/jcim.ahead-of-print/jcim-2015-0070/jcim-2015-0070.xml. doi: 10.1515/jcim-2015-0070. [Epub ahead of print]

PMID:26845728

Curcumin Attenuates Oxidative Stress and Activation of Redox-Sensitive Kinases in High Fructose- and High-Fat-Fed Male Wistar Rats.

Maithili Karpaga Selvi N, Sridhar MG, Swaminathan RP, Sripradha R.

Sci Pharm. 2014 Nov 4;83(1):159-75. doi: 10.3797/scipharm.1408-16. eCollection 2015.

PMID:26839808

Free PMC Article

Oral Probiotic VSL#3 Prevents Autoimmune Diabetes by Modulating Microbiota and Promoting Indoleamine 2,3-Dioxygenase-Enriched Tolerogenic Intestinal Environment.

Dolpady J, Sorini C, Di Pietro C, Cosorich I, Ferrarese R, Saita D, Clementi M, Canducci F, Falcone M.

J Diabetes Res. 2016;2016:7569431. doi: 10.1155/2016/7569431. Epub 2015 Dec 8.

PMID:26779542

Free PMC Article

Curcumin prevents paracetamol-induced liver mitochondrial alterations.

Granados-Castro LF, Rodríguez-Rangel DS, Fernández-Rojas B, León-Contreras JC, Hernández-Pando R, Medina-Campos ON, Eugenio-Pérez D, Pinzón E, Pedraza-Chaverri J.

J Pharm Pharmacol. 2016 Feb;68(2):245-56. doi: 10.1111/jphp.12501. Epub 2016 Jan 15.

PMID:26773315

Alternating or continuous exposure to cafeteria diet leads to similar shifts in gut microbiota compared to chow diet.

Kaakoush NO, Martire SI, Raipuria M, Mitchell HM, Nielsen S, Westbrook RF, Morris MJ.

Mol Nutr Food Res. 2016 Jan 14. doi: 10.1002/mnfr.201500815. [Epub ahead of print]

PMID:26767716

Curcumin prevents inflammatory response, oxidative stress and insulin resistance in high fructose fed male Wistar rats: Potential role of serine kinases.

Maithilikarpagaselvi N, Sridhar MG, Swaminathan RP, Zachariah B.

Chem Biol Interact. 2016 Jan 25;244:187-94. doi: 10.1016/j.cbi.2015.12.012. Epub 2015 Dec 20.

PMID:26713546

Curcumin protects against gallic acid-induced oxidative stress, suppression of glutathione antioxidant defenses, hepatic and renal damage in rats.

Abarikwu SO, Durojaiye M, Alabi A, Asonye B, Akiri O.

Ren Fail. 2016 Mar;38(2):321-9. doi: 10.3109/0886022X.2015.1127743. Epub 2015 Dec 27.

PMID:26707166

Curcumin upregulates Nrf2 nuclear translocation and protects rat hepatic stellate cells against oxidative stress.

Liu Z, Dou W, Zheng Y, Wen Q, Qin M, Wang X, Tang H, Zhang R, Lv D, Wang J, Zhao S.

Mol Med Rep. 2016 Feb;13(2):1717-24. doi: 10.3892/mmr.2015.4690. Epub 2015 Dec 17.

PMID:26676408

Curcumin Supplementation Decreases Intestinal Adiposity Accumulation, Serum Cholesterol Alterations, and Oxidative Stress in Ovariectomized Rats.

Morrone Mda S, Schnorr CE, Behr GA, Gasparotto J, Bortolin RC, da Boit Martinello K, Saldanha Henkin B, Rabello TK, Zanotto-Filho A, Gelain DP, Moreira JC.

Oxid Med Cell Longev. 2016;2016:5719291. doi: 10.1155/2016/5719291. Epub 2015 Nov 23.

PMID:26640615

Free PMC Article

Biological and therapeutic activities, and anticancer properties of curcumin.

Perrone D, Ardito F, Giannatempo G, Dioguardi M, Troiano G, Lo Russo L, DE Lillo A, Laino L, Lo Muzio L.

Exp Ther Med. 2015 Nov;10(5):1615-1623. Epub 2015 Sep 17.

PMID:26640527

Free PMC Article

Curcumin prevents the non-alcoholic fatty hepatitis via mitochondria protection and apoptosis reduction.

Wang L, Lv Y, Yao H, Yin L, Shang J.

Int J Clin Exp Pathol. 2015 Sep 1;8(9):11503-9. eCollection 2015.

PMID:26617882

Free PMC Article

Curcumin attenuates chronic ethanol-induced liver injury by inhibition of oxidative stress via mitogen-activated protein kinase/nuclear factor E2-related factor 2 pathway in mice.

Xiong ZE, Dong WG, Wang BY, Tong QY, Li ZY.

Pharmacogn Mag. 2015 Oct-Dec;11(44):707-15. doi: 10.4103/0973-1296.165556.

PMID:26600714

Free PMC Article

High Fat High Cholesterol Diet (Western Diet) Aggravates Atherosclerosis, Hyperglycemia and Renal Failure in Nephrectomized LDL Receptor Knockout Mice: Role of Intestine Derived Lipopolysaccharide.

Ghosh SS, Righi S, Krieg R, Kang L, Carl D, Wang J, Massey HD, Sica DA, Gehr TW, Ghosh S.

PLoS One. 2015 Nov 18;10(11):e0141109. doi: 10.1371/journal.pone.0141109. eCollection 2015.

PMID:26580567

Free PMC Article

Structural & functional consequences of chronic psychosocial stress on the microbiome & host.

Bharwani A, Mian MF, Foster JA, Surette MG, Bienenstock J, Forsythe P.

Psychoneuroendocrinology. 2016 Jan;63:217-27. doi: 10.1016/j.psyneuen.2015.10.001. Epub 2015 Oct 9.

PMID:26479188

T-Helper Cell-Mediated Islet Inflammation Contributes to β-Cell Dysfunction in Chronic Pancreatitis.

Talukdar R, Sasikala M, Pavan Kumar P, Rao GV, Pradeep R, Reddy DN.

Pancreas. 2016 Mar;45(3):434-42. doi: 10.1097/MPA.0000000000000479.

PMID:26474432

Curcumin Induces Pancreatic Adenocarcinoma Cell Death Via Reduction of the Inhibitors of Apoptosis.

Díaz Osterman CJ, Gonda A, Stiff T, Sigaran U, Valenzuela MM, Ferguson Bennit HR, Moyron RB, Khan S, Wall NR.

Pancreas. 2016 Jan;45(1):101-9. doi: 10.1097/MPA.0000000000000411.

PMID:26348467

Curcumin inhibits lung cancer invasion and metastasis by attenuating GLUT1/MT1-MMP/MMP2 pathway.

Liao H, Wang Z, Deng Z, Ren H, Li X.

Int J Clin Exp Med. 2015 Jun 15;8(6):8948-57. eCollection 2015.

PMID:26309547

Free PMC Article

Curcumin attenuates ethanol-induced hepatic steatosis through modulating Nrf2/FXR signaling in hepatocytes.

Lu C, Zhang F, Xu W, Wu X, Lian N, Jin H, Chen Q, Chen L, Shao J, Wu L, Lu Y, Zheng S.

IUBMB Life. 2015 Aug;67(8):645-58. doi: 10.1002/iub.1409. Epub 2015 Aug 25.

PMID:26305715

Curcumin pretreatment mediates antidiabetogenesis via functional regulation of adrenergic receptor subtypes in the pancreas of multiple low-dose streptozotocin-induced diabetic rats.

Naijil G, Anju TR, Jayanarayanan S, Paulose CS.

Nutr Res. 2015 Sep;35(9):823-33. doi: 10.1016/j.nutres.2015.06.011. Epub 2015 Jul 2.

PMID:26255758

Pancreatic β-Cells Limit Autoimmune Diabetes via an Immunoregulatory Antimicrobial Peptide Expressed under the Influence of the Gut Microbiota.

Sun J, Furio L, Mecheri R, van der Does AM, Lundeberg E, Saveanu L, Chen Y, van Endert P, Agerberth B, Diana J.

Immunity. 2015 Aug 18;43(2):304-17. doi: 10.1016/j.immuni.2015.07.013. Epub 2015 Aug 4.

PMID:26253786

iNKT and MAIT Cell Alterations in Diabetes.

Magalhaes I, Kiaf B, Lehuen A.

Front Immunol. 2015 Jul 2;6:341. doi: 10.3389/fimmu.2015.00341. eCollection 2015. Review.

PMID:26191063

Free PMC Article

Innate inflammation in type 1 diabetes.

Cabrera SM, Henschel AM, Hessner MJ.

Transl Res. 2016 Jan;167(1):214-27. doi: 10.1016/j.trsl.2015.04.011. Epub 2015 Apr 29. Review.

PMID:25980926

The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes.

Kostic AD, Gevers D, Siljander H, Vatanen T, Hyötyläinen T, Hämäläinen AM, Peet A, Tillmann V, Pöhö P, Mattila I, Lähdesmäki H, Franzosa EA, Vaarala O, de Goffau M, Harmsen H, Ilonen J, Virtanen SM, Clish CB, Orešič M, Huttenhower C, Knip M; DIABIMMUNE Study Group, Xavier RJ.

Cell Host Microbe. 2015 Feb 11;17(2):260-73. doi: 10.1016/j.chom.2015.01.001. Epub 2015 Feb 5.

PMID:25662751

Free PMC Article

The impact of diet and lifestyle on gut microbiota and human health.

Conlon MA, Bird AR.

Nutrients. 2014 Dec 24;7(1):17-44. doi: 10.3390/nu7010017. Review.

PMID:25545101

Free PMC Article

Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats.

Rashid K, Sil PC.

Toxicol Appl Pharmacol. 2015 Feb 1;282(3):297-310. doi: 10.1016/j.taap.2014.12.003. Epub 2014 Dec 23.

PMID:25541178

Curcumin ameliorates streptozotocin-induced liver damage through modulation of endoplasmic reticulum stress-mediated apoptosis in diabetic rats.

Afrin R, Arumugam S, Soetikno V, Thandavarayan RA, Pitchaimani V, Karuppagounder V, Sreedhar R, Harima M, Suzuki H, Miyashita S, Nomoto M, Suzuki K, Watanabe K.

Free Radic Res. 2015 Mar;49(3):279-89. doi: 10.3109/10715762.2014.999674. Epub 2015 Jan 28.

PMID:25536420

Free PMC Article

Curcumin improves high glucose-induced INS-1 cell insulin resistance via activation of insulin signaling.

Song Z, Wang H, Zhu L, Han M, Gao Y, Du Y, Wen Y.

Food Funct. 2015 Feb;6(2):461-9. doi: 10.1039/c4fo00608a.

PMID:25474544

Curcumin ameliorates testicular damage in diabetic rats by suppressing cellular stress-mediated mitochondria and endoplasmic reticulum-dependent apoptotic death.

Rashid K, Sil PC.

Biochim Biophys Acta. 2015 Jan;1852(1):70-82. doi: 10.1016/j.bbadis.2014.11.007. Epub 2014 Nov 11.

PMID:25446996

Free Article

The gut microbiota modulates glycaemic control and serum metabolite profiles in non-obese diabetic mice.

Greiner TU, Hyötyläinen T, Knip M, Bäckhed F, Orešič M.

PLoS One. 2014 Nov 12;9(11):e110359. doi: 10.1371/journal.pone.0110359. eCollection 2014.

PMID:25390735

Free PMC Article

Resveratrol and curcumin enhance pancreatic β-cell function by inhibiting phosphodiesterase activity.

Rouse M, Younès A, Egan JM.

J Endocrinol. 2014 Nov;223(2):107-17. doi: 10.1530/JOE-14-0335.

PMID:25297556

Free PMC Article

Exposure to a social stressor disrupts the community structure of the colonic mucosa-associated microbiota.

Galley JD, Nelson MC, Yu Z, Dowd SE, Walter J, Kumar PS, Lyte M, Bailey MT.

BMC Microbiol. 2014 Jul 15;14:189. doi: 10.1186/1471-2180-14-189.

PMID:25028050

Free PMC Article

Gut microbiota, probiotics and diabetes.

Gomes AC, Bueno AA, de Souza RG, Mota JF.

Nutr J. 2014 Jun 17;13:60. doi: 10.1186/1475-2891-13-60. Review.

PMID:24939063

Free PMC Article

Circadian disorganization alters intestinal microbiota.

Voigt RM, Forsyth CB, Green SJ, Mutlu E, Engen P, Vitaterna MH, Turek FW, Keshavarzian A.

PLoS One. 2014 May 21;9(5):e97500. doi: 10.1371/journal.pone.0097500. eCollection 2014.

PMID:24848969

Free PMC Article

A maternal gluten-free diet reduces inflammation and diabetes incidence in the offspring of NOD mice.

Hansen CH, Krych L, Buschard K, Metzdorff SB, Nellemann C, Hansen LH, Nielsen DS, Frøkiær H, Skov S, Hansen AK.

Diabetes. 2014 Aug;63(8):2821-32. doi: 10.2337/db13-1612. Epub 2014 Apr 2.

PMID:24696449

Free Article

Impact of stressor exposure on the interplay between commensal microbiota and host inflammation.

Galley JD, Bailey MT.

Gut Microbes. 2014 May-Jun;5(3):390-6. doi: 10.4161/gmic.28683. Epub 2014 Apr 1. Review.

PMID:24690880

Free PMC Article

Curcumin inhibits tumor growth and angiogenesis in an orthotopic mouse model of human pancreatic cancer.

Bimonte S, Barbieri A, Palma G, Luciano A, Rea D, Arra C.

Biomed Res Int. 2013;2013:810423. doi: 10.1155/2013/810423. Epub 2013 Nov 10.

PMID:24324975

Free PMC Article

Human intestinal microbiota and type 1 diabetes.

Vaarala O.

Curr Diab Rep. 2013 Oct;13(5):601-7. doi: 10.1007/s11892-013-0409-5. Review.

PMID:23934614

Curcumin attenuates diet-induced hepatic steatosis by activating AMP-activated protein kinase.

Um MY, Hwang KH, Ahn J, Ha TY.

Basic Clin Pharmacol Toxicol. 2013 Sep;113(3):152-7. doi: 10.1111/bcpt.12076. Epub 2013 May

PMID:23574662

Free Article

Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation.

Bailey MT, Dowd SE, Galley JD, Hufnagle AR, Allen RG, Lyte M.

Brain Behav Immun. 2011 Mar;25(3):397-407. doi: 10.1016/j.bbi.2010.10.023. Epub 2010 Oct 30.

PMID:21040780

Free PMC Article

Administration of different Lactobacillus strains in fermented oatmeal soup: in vivo colonization of human intestinal mucosa and effect on the indigenous flora.

Johansson ML, Molin G, Jeppsson B, Nobaek S, Ahrné S, Bengmark S.

Appl Environ Microbiol. 1993 Jan;59(1):15-20.

PMID:8439146

Free PMC Article

Effect of fermented oatmeal soup on the cholesterol level and the Lactobacillus colonization of rat intestinal mucosa.

Molin G, Andersson R, Ahrné S, Lönner C, Marklinder I, Johansson ML, Jeppsson B, Bengmark S.

Antonie Van Leeuwenhoek. 1992 Apr;61(3):167-73.