Thursday, October 27, 2016

Impressive results in overcoming allergies

Yesterday ScienceDaily published a press release about a new technique of developing immune tolerance of anaphylaxis-causing allergens in mice. The treatment resulted in significant effects with just one treatment in 90% of test cases.
The discovery involves generating a type of naturally occurring immune cell that sends a signal to reverse the hyper-immune response present in allergic reactions. That signal triggers another "off switch" that turns off reactive cells further along the allergic pathway.*Here's how the technique works:
•The key component of this research is dendritic cells, which serve as the gate-keepers of the immune system and are present in tissues in contact with the external environment, such as the skin and the inner lining of the nose, lungs, stomach and intestines.
•Gordon's pioneering treatment involves producing dendritic cells in a test tube and then exposing them to a unique mix of proteins, a vitamin A-related acid naturally occurring in the human gut, and to the allergen, in this case, peanut or ovalbumin (egg white protein). The modified dendritic cells are then reintroduced into the mouse.
•Using this technique, the researchers were able to nearly eliminate the allergic reaction by converting allergen-sensitive immune cells into cells that mimic the response seen in healthy, non-allergic individuals.
The treatment reduced the observed symptoms of anaphylaxis, and lowered other key protein markers in the allergic response by up to 90 per cent.

Per the abstract, they "generated and characterized mature retinoic acid-skewed dendritic cells." ( I can't read the whole study, but I'm very curious about what exactly they did with the retinoic acid. A few months ago, I hypothesized that excess retinoic acid was connected to developing food allergies ( and not in an inverse way; I thought that too much retinoic acid and its precursor retinal were interfering with RALDH2 activity, which appears crucial to immune tolerance. Perhaps I erred lumping retinal and retinoic acid together, or perhaps the timing of the exposure of the retinoic acid is crucial to developing the right kind of dendritic cell for reversing allergy. Or maybe while some retinoic acid is necessary to immune tolerance, an excess of retinoic acid causes the same problems as a deficiency, such as in this mouse study on excess Vitamin A, which found that it resulted in lower RALDH transcription subsequently - I will have to wait until the study has been published (it's still an "article in press") to evaluate whether my hypothesis is either weakened or strengthened by the success of this new technique. Either way, I'm pleased to see such solid progress in this field!

Wednesday, October 26, 2016


ScienceDaily just reported on a mouse study that found that the plant extract rutin helped diminish adiposity (i.e., lose weight):
To make their discovery, Jin and colleagues used both genetically obese mice and mice with diet-induced obesity as models. These mice were fed a regular diet, and supplemental rutin (1 mg/ml) was added to their drinking water. Rutin treatment significantly reduced adiposity, increased energy expenditure, and improved glucose homeostasis in both the genetically obese mice and the mice with diet-induced obesity. Specifically, the researchers found that rutin directly binds to and stabilizes SIRT1 (NAD-dependent deacetylase sirtuin-1), leading to hypoacetylation of PGC1α protein, which stimulates Tfam transactivation and eventually augments mitochondrial number and UCP1 activity in BAT. Rutin functions as a cold mimetic through activating a SIRT1-PGC1α-Tfam signaling cascade and increasing mitochondrial number and UCP1 activity in BAT. Rutin also induced brown-like (beige) adipocyte formation in subcutaneous adipose tissue in both obesity mouse models.

Among other things, rutin is an aldose reductase inhibitor. ( Rutin is found in buckwheat, cranberries, citrus fruits, and many other edible plants ( The rutin in buckwheat exhibits chelating and antioxidant activity, too. ( I wonder how buckwheat tastes....

Tuesday, October 25, 2016

Sketchy invitations

I recently received an email inviting me to submit an article to a recently-started journal and even promising an honorarium if it published my article in the near future. I have a lot of ideas in the journal's field of exploratory pharmacology, so I sat down and started drafting a short commentary and hypothesis tonight. Then I noticed an English error in the invitation email.

Being a curious type, I started to look further into this new journal. The alleged publisher has three other journals, all started within the past year or two. They claim that one of the journals has already begun being indexed on Pubmed. So I checked Pubmed. No, they're not indexed. And very few journal articles have been published according to the websites of their four journals. This claimed publisher appears to be a scam, for what purpose I know not. Perhaps they were going to reject my article and then later agree to publish it for a fee. But if it's not a reputable and/or indexed journal, their throwing my article up on their little website doesn't get my article any wider audience than my blog could.

Beware of journal scams. On the bright side, though, thanks to this dubious email invitation, I forced myself to set some good ideas down into a coherent short article that I can submit elsewhere.

Monday, October 24, 2016

Fair skin and Parkinson's

It's been repeatedly observed that fair skin is linked to an increased risk of Parkinson's. Melanin is natural pigment that causes skin to be brown or black. Neuromelanin is a similar molecule that is found in the brain and, while still rather mysterious, appears to help prevent cell death in some parts of the brain. ( Neuromelanin binds to (i.e., chelates) toxic metals, which helps protect the brain from them. (

A study in 2015 found that the lighter someone's skin, the more likely they were to have brain structure abnormalities associated with Parkinson's:

 2015 Nov;30(13):1848-52. doi: 10.1002/mds.26427. Epub 2015 Sep 23.
Light pigmentation phenotype is correlated with increased substantia nigra echogenicity.
This study was undertaken to address the question of whether pigmentation may be mechanistically linked withParkinson's disease.   METHODS:
In a cross-sectional, observational study, 116 healthy subjects received transcranial sonography of the substantia nigra. Pigmentation phenotype was assessed using the Fitzpatrick skin phototype classification, and five additional phenotypic pigmentation traits as well as a photographic method (Melanin index) in a subgroup of 46 subjects.   RESULTS:
Lighter skin phototype was associated with larger echogenic substantia nigra area and increased prevalence of abnormally enlarged echogenic substantia nigra area. The strongest association of substantia nigra echogenicity and phenotypic pigmentation traits was found for hair color and facial tanning.   INTERPRETATION:
Findings suggest an increasing prevalence of structural abnormality of substantia nigra with decreasing darkness of skin and thus may provide additional evidence in favor of a pathogenic link of pigmentation and Parkinson's disease.

Increased echogenicity of the substantia nigra is characteristically seen in Parkinson's disease. ( Not only do I get painful sunburns and have to worry about skin cancer,* but I also have a heightened risk of developing Parkinson's disease.

*Melanoma risk and Parkinson's risk are related -

Friday, October 21, 2016

Aldose reductase inhibition

Aldose (or aldehyde) reductase is inhibited by several substances, including isoliquiritigenin (which I've been discussing in connection with licorice) and rutin (which interestingly is in tea - Dietary sources of aldose reductase inhibition include spinach, cumin, fennel, lemon, basil, and black pepper. ( Aldose reductase is most known for its role in glucose metabolism, but it has other functions including in norepinephrine metabolism (

Here are some studies indicating effects of inhibiting aldose reductase:

That last one is probably the most relevant to my quest to discover how to not get Parkinson's.

Thursday, October 20, 2016


Licorice comes from two Greek terms meaning "sweet" and "root" and has been used for medicinal purposes for over 2000 years. (

The most well-known component of the licorice plant species is glycyrrhizin, which is very sweet and has some medical uses; however, excess consumption of glycyrrhizin can cause hypokalemia (low levels of potassium) and serious health problems. ( One can buy licorice supplements which have had the glycyrrhizin removed. (

Another component of licorice is isoliquiritigenin which, besides being a sirtuin-activating compound (, full text online at that could be good for fighting aging-related conditions ( and being a sleeping aid (, inhibits aldose reductase:
Traditionally in Japan, some kampo medicines (traditional oriental herbal prescriptions) have long been used for the treatment of diabetic neuropathy. We have found that some aldose reductase inhibitors are included among these drugs. We further investigated the components of glycyrrhizae radix, a constituent of some kampo medicines, and isolated six compounds (GUs 9-17). Among these, GU-17, identified as isoliquiritigenin, had the most potent aldose reductase inhibiting activity.

Tomorrow I'll go into how isoliquiritigenin's inhibition of aldose reductase might be helping the brain stave off Parkinson's. Apparently some scientists would argue with me that inhibition of aldose reductase does just the opposite:

Conference Paper: Aldose reductase-deficiency leads to more significant loss of dopaminergeric neurons with incresed levels of dopamine, tetrahydrobiopterin and free radical accumulation under experimental Parkinson's Disease condition

TitleAldose reductase-deficiency leads to more significant loss of dopaminergeric neurons with incresed levels of dopamine, tetrahydrobiopterin and free radical accumulation under experimental Parkinson's Disease condition
Issue Date2010
PublisherSociety for Neuroscience.
Neuroscience 2010 - 40th Annual Meeting, San Diego, CA., 13-17 November 2010. In Neuroscience 2010 - Final Program, 2010, Session 750, p. 20 Poster no. H15 How to Cite?

But they don't have a published paper that I can find, so I'm not sure what information or studies they base the title of their conference poster on. In general, searches on aldose reductase inhibition connect it with positive health outcomes. More tomorrow!

Wednesday, October 19, 2016

New topic - Parkinson's and smoking

I don't smoke. I never have and never will. Sometimes I find pleasing the smell of someone's else's cigarette wafting toward me from afar, but I have no desire to suck in all those poisons myself.

Smoking and smokeless tobacco are associated with lower Parkinson's risk, but not in those who have quit smoking. In fact, those who have quit smoking are more at risk of Parkinson's than those who have never smoked. ( That suggests that 1) something in cigarettes could be accumulating in the body (I suspect cadmium), and 2) something in cigarettes partially protects against whatever (cadmium-induced?) brain insults are killing off dopaminergic neurons.

I might have come across two good candidates for the protective component of cigarettes. The first is nicotine, which in small doses--nicotine is in several commonly-eaten foods--appears to have some helpful aspects, which I'll blog about later. Unfortunately, nicotine patches appear ineffective in treating Parkinson's (, so there's probably something else in cigarettes besides nicotine that is helping stave off Parkinson's. I suspect that second something is licorice. Isoliquiritigenin, a flavonoid in licorice (, can apparently protect dopaminergic neurons from dying:


Isoliquiritigenin isolated from licorice Glycyrrhiza uralensis prevents 6-hydroxydopamine-induced apoptosis in dopaminergic neurons.

Hwang CK, Chun HS.

Licorice (Glycyrrhiza uralensis) is a medicinal herb containing various bioactive components implicated in antioxidative, anti-inflammatory, antiviral, and neuroprotective effects, but the effects of licorice against Parkinson's disease (PD)-related dopaminergic cell death have not been studied. In this study, we investigated the protective effects of isoliquiritigenin (ISL) isolated from Glycyrrhiza uralensis on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in a dopaminergic cell line, SN4741. ISL (1 µM) significantly attenuated 6-OHDA (50 µM)-induced reactive oxygen species (ROS) and nitric oxide (NO) generation and apoptotic cell death. ISL pretreatment effectively suppressed 6-OHDA-mediated upregulation of Bax, p-c-Jun N-terminal kinase (JNK), p-p38 mitogen-activated protein (MAP) kinase, cytochrome c release, and caspase 3 activation. In addition, ISL significantly attenuated 6-OHDA-induced Bcl-2, brain-derived neurotrophic factor (BDNF), and mitochondrial membrane potential (MMP) reduction. Pharmacological inhibitors of the phosphatidylinositol 3-kinase (PI3K)-Akt/protein kinase B (PKB) pathway reversed ISL-mediated neuroprotection against 6-OHDA toxicity in SN4741 cells. These results provide the first evidence that ISL can protect dopaminergic cells under oxidative stress conditions by regulating the apoptotic process.

Most of the world's licorice production is used in tobacco products. ( Some licorice makes it way into black licorice candy and root beer, but here in the USA, licorice is a very common ingredient in cigarettes and smokeless tobacco.

As a non-smoker, I'll be doing much more research on this, for I've lived in places with bad air pollution and I prefer to avoid developing Parkinson's.

Tuesday, October 18, 2016


Once in a while, I get sinusitis and sinus headaches. I've tried different home remedies to open up the ostia (openings) between my sinuses and my nose in order to promote sinus draining: steam, herbal teas, eating raw garlic (not fun), massage, and attempts to create vacuums in my upper respiratory passages (plugging my ears and nose and inhaling).

I recently came across something new to try. Humming helps exchange air between the nose and the sinuses.

Here we show that nasal NO [nitric oxide] levels increases dramatically during humming compared with normal quiet nasal exhalation. This effect is likely due to increased contribution of NO from the paranasal sinuses. Humming causes the air to oscillate, which in turn seems to increase the exchange of air between the sinuses and the nasal cavity.

This exchange doesn't occur if the ostia are completely blocked, though. (

In 2006, a researcher in Sweden wrote a review on how humming affects ventilation between the sinuses and the nose. ( He mentions a case study where a man was able to clear out his sinuses by humming only: The case study was done by a man who used to sell zinc as a cure for colds, so I'm not sure how helpful it is, but it's interesting.

Humming has been tested and found to increase improvement of allergic rhinitis (hay fever) symptoms in patients who were given an intranasal steroid spray. ( Unfortunately for my curiosity, the institute ethical committee didn't allow the researchers in that study to have a third group that only did humming without any steroid treatment, so it's unclear whether the benefit from humming was from increased delivery of the steroid spray to the sinuses or from the mere act of humming.

Next time I feel my sinuses start to become clogged, I'll try humming. Humming seems harmless, and I might as well do what I can to keep the sinuses open before they become blocked and cause sinus headaches.

Monday, October 17, 2016

Gastroparesis and migraines connection is H2S?

In the past couple of months, I've blogged about molybdenum helping with migraines as well as a sulfite-molybdenum theory of nausea and vomiting in pregnancy (NVP) that includes a claim that pregnancy-induced gastroparesis could be occurring as a result of endogenous hydrogen sulfide (H2S) production.

If elevated hydrogen sulfide is helping cause both gastroparesis and migraines, then there should some connection between the two. It turns out there is an association :

Gastroparesis is a chronic disorder manifested by delayed emptying of the stomach. Gastroparesis is a relatively common complication of diabetes. In a population of patients with symptoms of diabetic gastroparesis, the patients with cyclic symptom patterns had a higher incidence of migraine headaches (47 vs. 20%, p = 0.02) compared to patients without cyclic vomiting pattern (). Migraine attacks are associated with delayed gastric emptying (). This migraine-associated gastroparesis is a problem for the treatment of the migraine with oral medicines, like oral triptans (). Initially, delayed gastric emptying was found during migraine attacks, now there are also indications that in the interictal periods migraine patients have delayed gastric emptying. However, the studies done so far have been small and inconsistent in their results (), so further research in this topic is warranted.

Could an H2S-synthesis inhibitor help prevent gastroparesis? If so, I first nominate the lowly common vetch. Obviously not for use during pregnancy (, but we know vetch contains beta-cyanoalanine, which inhibits two H2S-synthesizing enzymes ( A second possible suppressor of H2S biosynthesis is L-aminoethoxyvinylglycine (AVG) (, which is widely used to delay ripening of plums, apples, pears, and other fruits ( AVG is even approved for use on organic fruit ( Gastroparesis patients are unlikely to get much AVG in their diet, seeing as fruit peels are warned against in many dietary guidelines for them; even if they did eat fruit peels with AVG sprayed on them, any resulting H2S-reduction might be trivial.

I'd love for someone to test whether common vetch or AVG can lessen gastroparesis symptoms. And perhaps migraines, too.

Friday, October 14, 2016

Wrapping up morning sickness posts for now

I'm a little bored with researching nausea and vomiting of pregnancy (NVP). Probably because I'm not pregnant myself and know only one person in the early months of pregnancy right now. I have an acquaintance who is 11 weeks pregnant and seeing some benefit from using molybdenum; her "morning sickness" is mostly stomach discomfort rather than nausea this time around (it's her fifth pregnancy, I believe), which fits my hypothesis that endogenous hydrogen sulfide production in the abdomen is part of a healthy pregnancy but will also tend to cause slower gastric emptying.

I've addressed why many home and medical remedies can ameliorate NVP in accordance with my theory of sulfite accumulation causing NVP. The main medical remedies I haven't addressed are antihistamines (very sedating, though) and dopamine antagonists (can cause heart rhythm abnormalities, movement disorders, etc.), both of which do far more to the body than just help it bear NVP ( I'll probably post more later as I stumble across connections between sulfite and these two kinds of medication. For example, there are hints that serotonin and dopamine increase production of hydrogen sulfide, the precursor of sulfite (,

I hope my theory is correct so that multi-effect medications such as antihistamines only rarely need to be used during pregnancy. Sleeping through early pregnancy is better than being conscious and miserable, but most pregnant women would prefer to not have their activities curtailed quite so sharply. A little curtailment is a good thing, to be sure. I think training for a marathon during the period of placental development is unwise at best. That placenta is growing into the uterus's endometrium, and it seems best to not have the uterus rattling up and down constantly during that process. But there's a big difference between sitting down and being asleep.

Thursday, October 13, 2016


I really like pineapple. Not enough to do this dance, but then not everyone has such smooth moves:

Thank you, husband, for showing this to me so I can stay up to date on viral videos.

Last summer, a relative experienced sinus congestion and pain after eating cheesy pizza. I had some bromelain--an enzyme extracted from pineapple stems--with me, and I'd read about it being helpful for various things. I think I had gotten most of my information about bromelain from this paper: I gave my relative a pill or two of bromelain, and it made her sinus headache go away.

I think I've found a good argument in favor of pineapple pizza, which I enjoy even though many consider it an abomination. If the large quantity of cheese on a pizza can give one a sinus headache, then fresh pineapple with a little bromelain content is a logical addition to pizza.

A positive effect of bromelain on sinusitis symptoms has been found in clinical trials ( Why does bromelain help with sinus pain? Is it inflammation reduction? ( Thinning of nasal mucus? ( I don't know. I've experienced some relief when I have taken bromelain for sinus congestion and pain, but I don't like to take bromelain much because it seems to make my eyelashes droop into my eyes when I take it, which is annoying. Why would bromelain make my eyelashes turn toward my eyeballs anyway? I'm not comfortable with taking it regularly while all its effects remain unclear.

Plain pineapple, though, I'll happily eat in moderation. A 2014 article out of the Philippines reported that canned pineapple can lower the incidence of viral and bacterial infections in children (; this effect seems to have been from vitamins, not bromelain, as bromelain is an enzyme that is denatured by canning (

We need more research on bromelain to understand its effects on the body.

Wednesday, October 12, 2016

Why am I doing this nutrition research?

The first time I went outside the USA for more than a day trip was when I was 16 years old. My father took me out of school for a week (my grades didn't matter much because I was dropping out early to go to college the next fall anyway) so he could have a traveling companion on a trip to Cancun, Mexico. We went snorkeling, saw American college students get drunk, and visited Mayan ruins. But one of the things I found more intriguing than anything else was the local supermercado. Yes, I found the foreign grocery store to be an attraction. It had things I'd never seen before like fruit-flavored shelf-stable milk and bread with a giggle-worthy brand name ("Bimbo").

As years went by, I managed to get abroad a bit more. Germany, Poland, Austria, Philippines, South Korea, and then some countries in South America. And I continued to find the food stores one of the most interesting parts of my sojourns. I didn't care much about doing many typical touristy things, for beach outings left me sunburnt, but I loved seeing how the local people lived and learning about how they shopped for and ate food.

For the past three summers, our family has focused on learning about different countries: Russia, China, Germany, Lithuania, Zimbabwe, Bangladesh, Philippines, Japan, Peru, Mongolia, Canada, France, Italy, Senegal, Greece, Brazil, and Chile. For each country, I've read up about its cuisine so I could prepare meals for my family using typical foods from it. An unintended result for me was that I widened my knowledge of global eating patterns.

About a year ago, I took a free online course on vitamins from Wageningen University through EdX. My purpose in signing up for it was to learn information that would help me feed my family healthily. Not that I wasn't already feeding them fairly well, but I thought it would be good to know more about why fruits, vegetables, and whole grains were good for them.

Then about 10 months ago, I saw something talking about L-methylfolate being a better source of folate than folic acid. Due to a timing parallel between folic acid food fortification and the US's rise in autism, I'd been a little wary of folic acid supplementation for years. I still took folic acid during pregnancy, but my "regularly" wasn't the same as what my OB probably considered "regularly." 

So I looked into methylfolate and found myself falling down a rabbit hole of nutrition and medical research that I have yet to leave. And I don't want to leave it. The explosion of scientific knowledge in modern times and the unprecedented access that the internet gives us to even very recent findings has made this a great time to look at unsolved health problems from new angles, and my acquaintance with recipes and culinary preferences from other countries makes it easier for me to put together nutrition and epidemiology findings. I feel as though I'm doing math proofs, or at least connect-the-dot puzzles, with access to newly-discovered axioms and new data points. This is fun.

And that is why a stay-at-home homeschooling mother with degrees in law and math is posting what you find on this blog. No one pays me for it. Rather, someone would have to pay me to get me to stop.

Tuesday, October 11, 2016

Another molybdenum success story for migraine amelioration

Another friend who has suffered from migraines for years--she has to get weekly chiropractic adjustments to keep functioning due to her frequent migraines--tried molybdenum recently. She knew a bad migraine was coming on due to a weather shift (atmospheric pressure changes apparently trigger migraines in many who are prone to them), and took 250 mcg of a molybdenum supplement. Thirty minutes later her symptoms were noticeably reduced. After I told her that my first friend who tried molybdenum took a 500 mcg dose to make migraines go away, the second friend took an additional 250 mcg of molybdenum and experienced further benefit. She still had a headache--her migraines seem to be partly mechanical in origin, for they stem from something being damaged in her neck while doing pilates long ago--but it was bearable instead of the usual full-blown migraine.

She did experience one side effect: diarrhea, which is also something she experiences when she takes magnesium. The diarrhea is annoying enough that she is only going to take molybdenum when a migraine is coming on, but the molybdenum definitely helped her. If magnesium and molybdenum are supporting her body in turning sulfite into sulfate by facilitating suddenly higher levels of sulfite oxidase activity, diarrhea is exactly what one would expect to see, for there is anecdotal evidence that a sudden increase in sulfates in drinking water can trigger diarrhea and a 2012 study connected copper sulfate with diarrhea (

I've written to researchers in the field of migraines about sulfite possibly being a cause of migraine headaches, but the ones I contacted either ignored my emails or did not take seriously the possibility that sulfite could be involved. That is unfortunate, for there are many recently published research articles about how hydrogen sulfide, a precursor of sulfite, is made in the brain. I'll list a few here:

  • "In conclusion, H(2)S exerts a protective effect against cerebral hypoxia induced neuronal cell death via K(ATP)/PKC/ERK1/2/Hsp90 pathway. Our findings emphasize the important neuroprotective role of H(2)S in the brain during cerebral hypoxia."
  • Hydrogen sulfide as a neuromodulator.
  • "We as well as others have also shown that H2S has antioxidant, antiapoptotic, and anti-inflammatory properties against various neurodegenerative disorders such as stroke, Alzheimer's disease, and vascular dementia."
  • "During transsulfuration pathways, Hcy is metabolized into hydrogen sulfide (H2S), which is a synaptic modulator, as well as a neuro-protective agent."
  • "Hydrogen sulfide (H2S) is recognized as a neuromodulator as well as neuroprotectant in the brain. H2S can be produced from cysteine by enzymes such as cystathionine beta-synthase. However, a mechanism for releasing H2S under physiologic conditions has not been identified. Here we show that H2S is released from bound sulfur, an intracellular store of sulfur, in neurons and astrocytes of mice and rats in the presence of physiologic concentrations of endogenous reducing substances glutathione and cysteine. The highest pH to release H2S from another sulfur store, acid-labile sulfur, which is localized mainly in mitochondria, is 5.4. Because mitochondria are not in the acidic condition, acid-labile sulfur may not be a physiologic source of H2S. Free H2S is immediately absorbed and stored as bound sulfur. Our novel method, using silver particles to measure free H2S, shows that free H2S is maintained at a low level in basal conditions. Alkalinization of the cytoplasm is required for effective release of H2S from bound sulfur, and this condition is achieved in astrocytes by the high concentrations of extracellular K+ that are normally present when nearby neurons are excited."
  • "Hydrogen sulfide (H2S) has been recognized as a signaling molecule as well as a cytoprotectant. It modulates neurotransmission, regulates vascular tone, and protects various tissues and organs, including neurons, the heart, and kidneys, from oxidative stress and ischemia-reperfusion injury."
  • "Hydrogen sulfide (H2S), a novel gaseous mediator, has been recognized as an important neuromodulator and neuroprotective agent in the central nervous system. The present study was undertaken to study the effects of exogenous H2S on traumatic brain injury (TBI) and the underlying mechanisms. The effects of exogenous H2S on TBI were examined by using measurement of brain edema, behavior assessment, propidium iodide (PI) staining, and Western blotting, respectively. Compared to TBI groups, H2S pretreatment had reduced brain edema, improved motor performance and ameliorated performance in Morris water maze test after TBI. Immunoblotting results showed that H2S pretreatment reversed TBI-induced cleavage of caspase-3 and decline of Bcl-2, suppressed LC3-II, Beclin-1 and Vps34 activation and maintained p62 level in injured cortex and hippocampus post TBI. The results suggest a protective effect and therapeutic potential of H2S in the treatment of brain injury and the protective effect against TBI may be associated with regulating apoptosis and autophagy."
  • "Endogenous production of H2S in the brain was significantly inhibited by SAH. The protein levels of the predominant H2S-generating enzymes in the brain, including cystathionineb-synthase (CBS) and 3-mercaptopyruvate sulfur transferase (3MST), were also correspondingly reduced by SAH, while treatment with NaHS restored H2S production and the expressions of CBS and 3MST. More importantly, NaHS treatment could significantly attenuate EBI (including brain edema, blood-brain barrier disruption, braincell apoptosis, inflammatory response, and cerebral vasospasm) after SAH. In vitro, H2S protects neurons and endothelial function by functioning as an antioxidant and antiapoptotic mediator. "
  • "The current study indicates that H2S may function as an effective neuromodulator to regulate striatal neurotransmission and provides insight into the potential of H2S for PD therapy."
  • "Hydrogen sulfide (H(2)S), a well-known toxic gas, is regarded as endogenous neuromodulator and plays multiple roles in the central nervous system under physiological and pathological states, especially in secondary neuronal injury. Recent studies have shown relatively high concentrations of hydrogen sulfide (H(2)S) in the brain and also cytoprotective effects of endogenous and exogenous H(2)S in models of in vitro and in vivo ischemic injury. H(2)S protects neurons by functioning as an anti-oxidant, anti-inflammatory, and anti-apoptotic mediator and by improving neurological function. Moreover, it protects neurons from glutamate toxicity."

Moreover, we know that when someone becomes deficient in molybdenum, headaches are one of the symptoms of that deficiency ( Also, we now know that sulfite oxidase deficiency affects the brain starting in the cerebral cortex and striatum ( The cerebral cortex appears associated with migraine onset ( and exhibits abnormalities in migraine patients (

If any readers of this blog know a physician, medical researcher, naturopath, nutritionist, or chiropractor who would be interested in looking into a sulfite connection to migraines, please tell them about this possibility. Testing molybdenum supplements for migraine alleviation is much less controversial than testing it (or any supplement) on patients with nausea and vomiting of pregnancy, for no one wants to take the tiniest chance of harming a developing fetus (which is as it should be).

Monday, October 10, 2016

Lemons and nausea/vomiting

A common recommendation to ease nausea is the use of lemony beverages. I came across research published last week that ties citral and linalool, both oils found in citrus fruits, to inhibition of 5-HT3 receptors, which as discussed in my last post blocks signals to the brain that are involved in vomiting.
Noncompetitive Inhibition of 5-HT3 Receptors by Citral, Linalool, and Eucalyptol Revealed by Nonlinear Mixed-Effects Modeling.
Jarvis GE, Barbosa R, Thompson AJ. Abstract: Citral, eucalyptol, and linalool are widely used as flavorings, fragrances, and cosmetics. Here, we examined their effects on electrophysiological and binding properties of human 5-HT3 receptors expressed in Xenopus oocytes and human embryonic kidney 293 cells, respectively. Data were analyzed using nonlinear mixed-effects modeling to account for random variance in the peak current response between oocytes. The oils caused an insurmountable inhibition of 5-HT-evoked currents (citral IC50 = 120 µM; eucalyptol = 258 µM; linalool = 141 µM) and did not compete with fluorescently labeled granisetron, suggesting a noncompetitive mechanism of action. Inhibition was not use-dependent but required a 30-second preapplication. Compound washout caused a slow (∼180 seconds) but complete recovery. Coapplication of the oils with bilobalide or diltiazem indicated they did not bind at the same locations as these channel blockers. Homology modeling and ligand docking predicted binding to a transmembrane cavity at the interface of adjacent subunits. Liquid chromatography coupled to mass spectrometry showed that an essential oil extracted from Lippia alba contained 75.9% citral. This inhibited expressed 5-HT3 receptors (IC50 = 45 µg ml(-1)) and smooth muscle contractions in rat trachea (IC50 = 200 µg ml(-1)) and guinea pig ileum (IC50 = 20 µg ml(-1)), providing a possible mechanistic explanation for why this oil has been used to treat gastrointestinal and respiratory ailments. These results demonstrate that citral, eucalyptol, and linalool inhibit 5-HT3 receptors, and their binding to a conserved cavity suggests a valuable target for novel allosteric modulators.

What is citral found in? Lemony things. Lemon myrtle, lemongrass, lemon balm, lemon, lime, and orange juice. (
Next, linalool is found in many plants, including ginger, may chang, some laurels and basils, coriander, and lavender. (, Finally, eucalyptol is found in eucalyptus, tea tree, mugwort, bay leaves, and cannabis. (

Are these three oils safe? It depends on the dosage. Eucalyptol is known to have caused deaths from overuse. Also, if obtaining oils from plants, one is getting other oils and substances along with those particular plants. For example, I could never recommend using cannabis for nausea and vomiting of pregnancy because of its known effects, which include an increased risk of preterm birth ( and altered fetal brain development ( On the other hand, regular food-level uses of citral (such as in lemony beverages) and linalool (ginger!) appear to be time-tested, safe home helps for nausea.

Saturday, October 8, 2016

How Zofran's effectiveness lends support to a sulfite theory of NVP

The chemotherapy drug ondansetron (Zofran) is frequently prescribed off-label to treat hyperemesis gravidarum (, the severe form of nausea and vomiting in pregnancy (NVP). Zofran appears quite effective at decreasing severe vomiting (but not necessarily the feeling of nausea) for many women (, but its use is still controversial due to possible connections to birth defects ( and unclear evidence of relative effectiveness compared to other antiemetics (

Zofran works by antagonizing, i.e., blocking, 5-HT3 (serotonin) receptors ( in both the central nervous system and the gastrointestinal tract.

Signals involved in chemotherapy-induced nausea and vomiting. Image is from "Nausea and vomiting with high-dose chemotherapy and stem cell rescue therapy: a review of antiemetic regimens." M E Trigg and D M Inverso. Bone Marrow Transplant (2008) 42:501-506. (
In my sulfite-molybdenum theory of NVP (, I compare the accumulation of toxic sulfite in the gastrointestinal tract to taking syrup of ipecac, which brings on vomiting by irritating the lining of the stomach. Interestingly, Zofran completely does away with the emetic effect of ipecac, per this study that was actually focused on marijuana (it did find a small NVP amelioration from marijuana but not one worth the side effects) ( Thus, if sulfite is irritating pregnant women's stomach lining as I hypothesize is happening, Zofran could be ameliorating sulfite-related vomiting the same way it does with ipecac.

It seems to me that the less risky way to address sulfite irritation is to help the body break down sulfite into sulfate (via support of the enzyme sulfite oxidase) and pass sulfite out of the gastrointestinal tract more quickly (via measures to speed gastric emptying) rather than working to block sulfite's effects on the 5-HT3 receptors, for the 5-HT3 receptors have other jobs to do in the body (,,,, besides mediate vomiting. Also, there will still be sulfite in the stomach and intestine which could continue to damage the mucosal lining. Unless my theory is disproven, I cannot get behind widespread use of Zofran for NVP.

Thursday, October 6, 2016

Can magnesium help with nausea and vomiting of pregnancy?

There are many blogs touting magnesium as a cure for "morning sickness" or nausea and vomiting of pregnancy (NVP). A quick search of PubMed just now didn't turn up studies where magnesium was tested as a help for NVP. I did find one study showing that over the course of pregnancy, women with NVP tend to intake less B12 and magnesium (

If magnesium is helping alleviate NVP for some women, how is it doing it? As I was researching the enzyme sulfite oxidase recently, I came across an article describing how the molybdenum cofactor, which is incorporated into sulfite oxidase, is formed ( It appears that the process of forming the molybdenum cofactor relies on magnesium in three different places:

Magnesium (Mg) is used three times in the process of forming the molybdenum cofactor (MoCo). Image from "The Molybdenum Cofactor," Ralf R. Mendel* (2013). The Journal of Biological Chemistry 288:13165-13172, 13167.

Supporting the formation of sulfite oxidase (and thus the speedy conversion of nausea-inducing sulfite to sulfate) requires getting enough magnesium. I don't see a reason to give large amounts of supplemental magnesium, but being deficient in magnesium seems as though it could contribute to NVP and so should be avoided.

* I want to note here that Ralf R. Mendel is one of my heroes. He has done painstaking, thorough research for years on molybdenum-containing enzymes and much of my recent research has depended in part on his work.

Wednesday, October 5, 2016

Why does vitamin B6 help with NVP sometimes?

Some women have found that vitamin B6 (the active form of which is pyridoxal 5'phosphate, PLP, or P5P) helps lessen their nausea and vomiting of pregnancy (NVP). (See Why does it help them? I believe I may have found at least a partial answer that is predicted by my sulfite-molybdenum theory of "morning sickness."

The enzyme sulfite oxidase, which catalyzes the conversion of sulfite to sulfate, contains two important parts: 1) molybdenum, and 2) cytochrome b5 type heme (

Where does heme come from? We make it, generally, out of iron, although sometimes we get it directly from food. Heme is a form of iron that is in meat and is especially high in animal liver (

While liver contains many great nutrients, it should not be overdone during pregnancy due to the high amount of fat-soluble Vitamin A in it. A friend found that some pills high in dried liver (and recommended by her naturopath friend) made her morning sickness go away during a pregnancy two years ago, but she didn't take the pills regularly due to concerns about taking high levels of supplements; when she didn't take the pills, she was "sick as a dog," but given the amount of Vitamin A that might have been in the pills, I think she was wise to limit her intake of them. Fat-soluble vitamins are more prone to build up in the body, and too much Vitamin A from animal sources is known to be harmful to a developing fetus. Defatted liver pills should theoretically be a safer source of heme during pregnancy than non-defatted liver. After all, the reason the government requires adding Vitamin A to our skim, 1%, and 2% milk is to make up for the Vitamin A loss that results from cream removal. However, I am still looking into just how much Vitamin A is left in liver after the fat is removed.

Non-animal source iron is turned into heme in our bodies during a multi-step process that has been well-researched. The first step in the biosynthesis of heme depends on the enzyme aminolevulinic acid synthase, which is one of the many enzymes in our bodies that requires PLP as a cofactor (,

Therefore, if a pregnant woman is not eating a lot of heme but does get enough iron from other sources, PLP supplementation could enhance the conversion of that iron into heme, which would then be available for use in sulfite oxidase. This in turn can help keep sulfite from accumulating in the body--sulfite accumulation apparently chemically "traps" PLP (, too, which is undesirable due to the many enzymes that depend on PLP--and so alleviate nausea and vomiting induced by sulfite in the stomach and intestines. However, a woman who already gets enough heme in her diet or who is deficient in molybdenum would be unlikely to receive much NVP-related benefit from PLP (i.e., vitamin B6) supplementation.

Tuesday, October 4, 2016

Excess folic acid linked to extra weight gain when part of a high fat diet

Since I brought up folic acid yesterday, here's a bit more on it. A study published in September found that excess folic acid exacerbated weight gain in mice fed high-fat diets:
 2016 Sep 23;8(10). pii: E594. doi: 10.3390/nu8100594.

Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats.

Abstract: Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet.

Having definitely not eaten an excess of folic acid for about 8 months now and seen no resulting diminishment in adiposity, I can be confident that I don't feed my family or myself a high fat diet.

Monday, October 3, 2016

Seasonal variation in nutrients

I live in a place with four seasons, and I love it when the leaves start changing and I can buy recently-pressed apple juice at the grocery store. Squash, apples, and grapes are fresh and relatively inexpensive in the fall. It's one of the tastiest times of year.

Then comes winter with savory stews using root crops, meat, and grain. And I'm always happy to see spring and summer again, with fresh produce coming back to the supermarkets as it grows and ripens. The different foods of each season help me vary my diet, which I've come to realize is very important for two reasons:

1) Homeostasis, or "the ability to maintain a constant internal environment in response to environmental changes." ( Our bodies do visible, obvious things to maintain constancy in many circumstances. A common example used in biology lessons about homeostasis in humans covers how we sweat to stay cool and shiver to keep warm. But we also do less obvious things such as downregulate production of certain molecules when there is extended exposure to a nutrient or stimulant that interacts with that molecule. (E.g., and

Periodic rotation of the foods we eat can prevent unintentional long-term overdosing on any one nutrient. As part of my religion, I also go without food and drink (except water) for approximately 24 hours once each month, which helps me have short, scheduled breaks from pretty much every nutrient. As long as I don't gorge on chocolate cake right after ending the fast, it seems to be a good thing for my health, and there are studies supporting the health benefits of periodic breaks from food (E.g,

2) Extreme eating is frequently problematic, and varying foods with the seasons helps avoid it. I don't know if extreme eating is more often a cause or a symptom of mental illness, but my observations over the past decade have been that extreme eating habits and mental illness seem to go together. What is extreme eating? I think it encompasses any kind of eating philosophy that overrides the fundamental human need to be well-nourished. If one's eating philosophy causes malnourishment or obvious physical symptoms of illness, that's a sign that it's extreme. Nutritionists keep repeating mantras about "healthy, varied diets" because too much of a good thing often turns into a bad thing.

Too much avoidance of perceived "bad" foods can also be extreme eating. There's a name for that, "orthorexia nervosa:"
The term was introduced in 1997 by American physician Steven Bratman, M.D., who suggests that in some susceptible people, dietary restrictions intended to promote health may paradoxically lead to unhealthy consequences, such as social isolation, anxiety, loss of ability to eat in a natural, intuitive manner, reduced interest in the full range of other healthy human activities, and, in rare cases, severe malnutrition or even death. (accessed October 3, 2016)

I'm mindful of the need to avoid my nutrition research giving my children orthorexia. For instance, I'm no fan of folic acid or cyanocobalamin, and they know it. But I still buy foods with small amounts of them for my children and myself sometimes because I have seen no evidence of small amounts causing harm to our family specifically or in scientific studies. At social events, our family eats whatever tasty snacks appeal to them...even Oreos, which are definitely just a "sometimes treat." Human bodies have mechanisms to detoxify and excrete harmful substances, and we can generally rely on those mechanisms as long as we don't overwhelm them with large quantities of harmful substances or have genetic susceptibilities to those substances.