Thursday, September 28, 2017

Update on excess folic acid findings

A little over a year ago, my friend and I wrote a letter to the editor in which we expressed concern that excess folic acid was linked to the rise in attention-deficit hyperactivity disorder and autism spectrum disorders:

https://www.ncbi.nlm.nih.gov/pubmed/27346490: "Unintended consequences of inhibiting dihydrofolate reductase through folic acid supplementation: inattentive-type attention deficit hyperactivity disorder and ASD connections."

Two recent studies indicate that excess folic acid during pregnancy causes--in mice and people-- diminished cognitive function in the offspring:

https://www.ncbi.nlm.nih.gov/pubmed/28069796: "High dietary folate in pregnant mice leads to pseudo-MTHFR deficiency and altered methyl metabolism, with embryonic growth delay and short-term memory impairment in offspring."

https://www.ncbi.nlm.nih.gov/pubmed/28724645: "Effect of maternal high dosages of folic acid supplements on neurocognitive development in children at 4-5 y of age: the prospective birth cohort Infancia y Medio Ambiente (INMA) study."

I expect more studies will come out with similar results over the next few years. Folic acid just isn't a typical molecule in the human body or diet.

Tuesday, September 26, 2017

Licorice might be a cognitive enhancer

A year ago, I mused that licorice might be behind the protective effect that smoking tobacco has against developing Parkinson's. I looked specifically at its component isoliquiritigenin. But there's interesting recent research about another licorice molecule: liquiritigenin. It appears it could be a memory enhancer.

Biomol Ther (Seoul). 2017 May 30. doi: 10.4062/biomolther.2016.284. [Epub ahead of print]
The Memory-Enhancing Effects of Liquiritigenin by Activation of NMDA Receptors and the CREB Signaling Pathway in Mice.

Ko YH, Kwon SH, Hwang JY, Kim KI, Seo JY, Nguyen TL, Lee SY, Kim HC, Jang CG.

Abstract: Liquiritigenin (LQ) is a flavonoid that can be isolated from Glycyrrhiza radix [licorice]. It is frequently used as a tranditional oriental medicine herbal treatment for swelling and injury and for detoxification. However, the effects of LQ on cognitive function have not been fully explored. In this study, we evaluated the memory-enhancing effects of LQ and the underlying mechanisms with a focus on the N-methyl-D-aspartic acid receptor (NMDAR) in mice. Learning and memory ability were evaluated with the Y-maze and passive avoidance tests following administration of LQ. In addition, the expression of NMDAR subunits 1, 2A, and 2B; postsynaptic density-95 (PSD-95); phosphorylation of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII); phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2); and phosphorylation of cAMP response element binding (CREB) proteins were examined by Western blot. In vivo, we found that treatment with LQ significantly improved memory performance in both behavioral tests. In vitro, LQ significantly increased NMDARs in the hippocampus. Furthermore, LQ significantly increased PSD-95 expression as well as CaMKII, ERK, and CREB phosphorylation in the hippocampus. Taken together, our results suggest that LQ has cognition enhancing activities and that these effects are mediated, in part, by activation of the NMDAR and CREB signaling pathways.

https://www.ncbi.nlm.nih.gov/pubmed/28554200

I like the taste of the deglycyrrhizinated licorice tablets I bought a year ago and stuck in the fridge. Maybe I'll pull those out and see if I notice a memory-enhancing effect. Of course, now that I've read the research above, there's no way to rule out a placebo effect in me. Also, I'm not suffering memory problems. I need to find someone who is complaining of memory issues and see if they want to try licorice....

Sunday, September 24, 2017

And another molybdenum/migraine success

A colleague was out with a five-day migraine a week ago. Guess what I told her about? Of course. And she tried it. She was able to come back to work (that's how I saw her to give her some molybdenum) but still had the migraine lingering and threatening to descend again, so she took 1000 mcg of molybdenum glycinate. Ninety minutes later, I saw her helping push someone else's broken-down automobile and reporting that the molybdenum had helped her.

Thursday, September 21, 2017

Oyster heme & possible RLS

Oysters are really high in heme (a kind of iron) content. (https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/) I ate a lot of oysters (canned, not fresh) yesterday because I wanted the zinc and glycine betaine in them. Oysters are fairly foreign to me, and I had forgotten about their high heme content. Over a year ago, I wrote (http://petticoatgovernment.blogspot.com/2016/07/carbon-monoxide-and-restless-legs_15.html) that restless legs syndrome appears to me to be endogenous carbon monoxide excess in the leg muscles, which carbon monoxide is a metabolic product of heme, and so I suggested that people dealing with restless legs syndrome avoid overconsuming heme. 

Guess what woke me at 4 am this morning? This weird feeling in my legs....

I took a hydroxocobalamin lozenge (also suggested in my year-old post as a help since it combined with Vitamin C appears to be a possible treatment for carbon monoxide poisoning) and was able to fall back asleep soon after. My legs still feel a little weird this morning, and I have a bit of a "steely" feeling in my head. So I'll take more hydroxocobalamin and some Vitamin C now, and then I'll set to figuring out why I'm so sensitive to heme intake. It was just one can of oysters! (Which I ate all by myself.)

Wednesday, September 13, 2017

One-page summary of nutrition to promote proper methylation

Here is a one-page summary of some of what I consider the most valuable information I've gathered on nutritional factors that promote proper methylation, which appears to help with ADHD, autism spectrum disorders, and possibly preventing cancer. Feel free to share (without alteration, please) as widely as you like.


Wednesday, September 6, 2017

Recent research roundup

I often have tabs on my browser that I leave open for a week or more because I've been looking into a subject but haven't collected enough interesting material to write a whole blog post. Tonight I'm going to link to my open pages so that I can finally close them on my browser. One tab is connected to hydrogen peroxide and antioxidants, which tangentially goes along with our family research project of testing all our produce for catalase action. (If you want to have fun, put some mushed banana in a glass then pour in some 3% hydrogen peroxide; the results are slow but impressive.) A couple are about iron overload and its possible connection to mental health condition exacerbation (I'm curious as to whether there's a link between fluctuating iron stores in women and symptom severity.). And the rest are my research into whether there is anything special in chicken gizzards, which topic became one of interest a couple weeks ago after I noted that chicken gizzard soup, which I'd never cooked before, made me feel unusually happy and peaceful; the research led me to MUC1, a mucin in gizzards which is upregulated by GABA and which I suspect might help people feel calm (That could contribute to the common relaxed feeling after Thanksgiving dinner, which is the only time Americans tend to eat gizzard--it's part of giblets--broth on the same day. People wouldn't have noticed as large an effect from eating fried gizzards because they usually boil then dry gizzards before coating and frying them; no broth consumed. I think MUC1 might be heat stable at 100C, given that mucin in cooked okra is what makes it so slimy, but I couldn't find any clear evidence of that, only that it's very resistant to heat denaturation at temperatures up to 85C. There are also water-soluble forms of MUC1, which could explain how MUC1 would end up in gizzard broth instead of staying in the rubbery gizzard pieces in my soup. MUC1 is overexpressed in many cancers, so I'm sure much more research on it will be forthcoming.). Kind of random, but that's what roundups are for.

**

Antioxidant effect of red wine anthocyanins in normal and catalase-inactive human erythrocytes. http://www.sciencedirect.com/science/article/pii/S0955286301001644 “Subsequently, we demonstrate that fractions containing anthocyanins lower ROS (reactive oxygen species) and methemoglobin production in human erythrocytes treated with H2O2. Finally, we reported that the protective effects of anthocyanins were also confirmed in an experimental model in which RBCs were deprived of catalase activity by treatment with 4 mM sodium azide. The results obtained clearly demonstrate that red wine anthocyanins protect human RBCs from oxidative stress.”

Iron overload and psychiatric illness. https://www.ncbi.nlm.nih.gov/pubmed/8194001
Abstract: Seven patients with varying psychiatric disorders were found to have iron overload as manifested by abnormal serum ferritin, transferrin saturation index (TSI), or excessive urinary iron. All possible sources of secondary iron overload were ruled out. The patients were treated with the specific iron chelator, deferoxamine, given IM for seven to 22 weeks which resulted in significant clinical improvements. These cases indicate a need to be aware that disordered iron metabolism is a somatic cause of psychiatric illness and that there is clinical improvement upon lowering elevated iron levels in patients with iron overload.

Hemochromatosis-induced bipolar disorder: a case report. http://www.sciencedirect.com/science/article/pii/S0163834311001368
Abstract
Objective - A patient presenting with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, bipolar disorder was found to be affected by high iron hemochromatosis. This prompted us to explore the relation between bipolar disorder and iron overload.
Method - We report the case and review the peer-reviewed literature focusing on mood symptoms in patients with hemochromatosis or iron overload. Animal studies of brain effects of iron overload are summarized. High iron hemochromatosis was confirmed by genetic testing, and treatment was instituted to address iron overload.
Results -Patient's bipolar symptoms completely subsided after phlebotomic reduction of iron overload.
Conclusion - Clinicians should explore the possibility of iron overload and seek genetic confirmation of hemochromatosis in resistant bipolar disorder to avoid unnecessary medication.

Structure of the glandular layer and koilin membrane in the gizzard of the adult domestic fowl (Gallus gallus domesticus). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1261543/?page=1

Histomorphological and Histochemical Studies of the Stomach of the Mallard (Anas platyrhynchos) http://scialert.net/fulltext/?doi=ajas.2015.280.292 “Rossi et al. (2005) observed in the gizzard’s mucosa of the partridge (Rhynchotus rufescens) low folds lined by simple columnar to cuboidal epithelium. The mucosa revealed the presence of tubular glands, which were lined by low cuboidal at their bases, whereas higher at their upper portions. In fact, the luminal surface of the gizzard was lined with secretory product of the mucosal glands, which solidified at the surface to form a hard cuticle of koilin. Selvan et al. (2008) recorded that the gizzard’s wall of the guinea fowl (Numida meleagris) constructed from the usually known four tunics in addition to an internal lining of koilin which was a secretary layer above the mucosa. The koilin showed positive reaction with the PAS. The surface epithelium was PAS positive too. They showed predominance of neutral mucin. The PAS positive material was present in the lumen of the glands and in the cells that were lined both the surface and crypts.”

The differences between the localizations of MUC1, MUC5AC, MUC6 and osteopontin in quail proventriculus and gizzard may be a reflection of functional differences of stomach parts. http://onlinelibrary.wiley.com/doi/10.1111/j.1469-7580.2010.01243.x/full “In conclusion, the expressions of MUC1, MUC5AC, MUC6 and OPN in quail proventriculus and gizzard were different. These differences may be a reflection of functional differences of stomach parts. In addition, the localization of MUC5AC in proventriculus was different from those of MUC1, MUC6 and OPN. The immunoreactivity of MUC5AC was present in the lining epithelium of both folds and superficial proventricular glands in the proventriculus, whereas MUC1, MUC6 and OPN reactivity was found in the oxynticopeptic cells of profound proventricular glands. Furthermore, the immunoreactivity of MUC1 in gizzard was different from that of MUC5AC. Although MUC5AC was expressed in the cells of surface epithelium and profound glands of the gizzard, MUC1 was localized in the simple tubular profound glands of the gizzard. However, MUC6 and OPN immunoreactivity was absent in the gizzard. These differences may also be a reflection of the functional differences between the surface epithelial cells and glandular cells of both the proventriculus and gizzard.”

Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3221539/. The top biological function pathway in the SZ gene list was ‘psychological disorders’, comprising nine genes directly implicated in SZ (CCND2, CHRNA2, FXR2, FXYD6, HRH3, MUC1, PFN2, SLC31A2, SLC6A3) (P= 3.64E − 03).

GABA selectively increases mucin-1 expression in isolated pig jejunum. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607675/ “Porcine jejunum epithelial preparations were incubated with two different amounts of GABA or glutamine on the mucosal side for 4 h, and changes in the relative gene expression of seven different mucins, enzymes involved in mucin shedding, GABA B receptor, enzymes involved in glutamine/GABA metabolism, glutathione peroxidase 2, and interleukin 10 were examined by quantitative PCR (TaqMan® assays). Protein expression of mucin-1 (MUC1) was analyzed by Western blot. On the RNA level, only MUC1 was significantly up-regulated by both GABA concentrations compared with the control. Glutamine-treated groups showed the same trend. On the protein level, all treatment groups showed a significantly higher MUC1 expression than the control group. We conclude that GABA selectively increases the expression of MUC1, a cell surface mucin that prevents the adhesion of microorganisms, because of its size and negative charge, and therefore propose that the well-described positive effects of glutamine on enterocytes and intestinal integrity are partly attributable to effects of its metabolite GABA.”

Oral intake of γ-aminobutyric acid affects mood and activities of central nervous system during stressed condition induced by mental tasks. https://www.ncbi.nlm.nih.gov/pubmed/22203366 “In this study, we investigated how the oral intake of GABA influences human adults psychologically and physiologically under a condition of mental stress. Sixty-three adults (28 males, 35 females) participated in a randomized, single blind, placebo-controlled, crossover-designed study over two experiment days. Capsules containing 100 mg of GABA or dextrin as a placebo were used as test samples. The results showed that EEG activities including alpha band and beta band brain waves decreased depending on the mental stress task loads, and the condition of 30 min after GABA intake diminished this decrease compared with the placebo condition. That is to say, GABA might have alleviated the stress induced by the mental tasks. This effect also corresponded with the results of the POMS scores.”


Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. https://www.ncbi.nlm.nih.gov/pubmed/16971751 “The effect of orally administrated gamma-aminobutyric acid (GABA) on relaxation and immunity during stress has been investigated in humans. Two studies were conducted. The first evaluated the effect of GABA intake by 13 subjects on their brain waves. Electroencephalograms (EEG) were obtained after 3 tests on each volunteer as follows: intake only water, GABA, or L-theanine. After 60 minutes of administration, GABA significantly increases alpha waves and decreases beta waves compared to water or L-theanine. These findings denote that GABA not only induces relaxation but also reduces anxiety. The second study was conducted to see the role of relaxant and anxiolytic effects of GABA intake on immunity in stressed volunteers. Eight acrophobic subjects were divided into 2 groups (placebo and GABA). All subjects were crossing a suspended bridge as a stressful stimulus. Immunoglobulin A (IgA) levels in their saliva were monitored during bridge crossing. Placebo group showed marked decrease of their IgA levels, while GABA group showed significantly higher levels. In conclusion, GABA could work effectively as a natural relaxant and its effects could be seen within 1 hour of its administration to induce relaxation and diminish anxiety. Moreover, GABA administration could enhance immunity under stress conditions.”