Friday, September 30, 2016

Triangular teeth

About a decade ago, I lived in Manila, Philippines for a while. I met a couple of US college students who were working with street children in Manila. Anyone who thinks poverty in the US is just the worst needs to look outside this country to see how much worse it can get. (https://en.wikipedia.org/wiki/Street_children_in_the_Philippines) The street children in Manila beg and sell flowers in the street, weaving around traffic and breathing in exhaust. It is common for them to inhale dangerous chemicals like glue. They have awful tooth decay because carbonated beverages are cheaper than milk, so they drink a lot of cola and other soda pop; on numerous occasions I saw young Filipino children with mouths full of triangular teeth from tooth decay.

Primary teeth are more susceptible to tooth decay from soda pop than are "adult" teeth:
Comparison of the microhardness of primary and permanent teeth after immersion in two types of carbonated beverages.
OBJECTIVES:
The consumption of carbonated beverages is one of the etiological factors that cause dental erosion. The purpose of this research was to compare changes in the microhardness of permanent and primary teeth after immersion in two types of carbonated beverages.MATERIALS AND METHODS:
This investigation was done on 30 healthy permanent molars and 30 healthy primary canines. Each group of primary and permanent teeth was subdivided into three groups of 10 teeth. The teeth was immersed in 40 ml of each of the three beverages for 5 min. One subgroup was immersed in water (as a control). The next was immersed in Lemon Delster and the last subgroup was immersed in Coca-Cola. The microhardness of enamel was measured using the Vickers method before and after immersion. Finally, the data was analyzed by paired t-test, one-way analysis of variance, and t-test.RESULTS:
Microhardness reduction in the primary teeth was significant in both the Lemon Delster and Coca-Cola groups (P < 0.05). This reduction was also statistically significant in the permanent teeth (P < 0.05). A comparison of the enamel changes in the primary teeth with permanent teeth after immersion in both beverages showed a greater microhardness reduction in the primary teeth in both the experimental groups.CONCLUSIONS:
Coca-Cola and Lemon Delster caused a significant reduction of microhardness in tooth enamel. This reduction was greater in primary teeth than in permanent teeth, and was also greater after immersion in Coca-Cola than after immersion in Lemon Delster.

Thursday, September 29, 2016

Flat soda

Diet recommendations for dealing with nausea and vomiting often include flat (i.e., no longer fizzy) carbonated beverages (http://antoine.frostburg.edu/chem/senese/101/consumer/faq/antinausea-syrup.shtml), or "soda pop" as I call it as a compromise between my western states heritage and my current, more central location (see http://whatpeopleknow.blogspot.com/2011/09/pop-vs-soda-vs-coke.html).

Why is it less problematic to drink the soda pop after the bubbles have all gone away? I was surprised to see that carbonated beverages do not slow down gastric emptying. What they do is alter the location of the stomach contents a bit:

 1997 Jan;42(1):34-9.
Effect of carbonated water on gastric emptying and intragastric meal distribution.
Carbonated water has long been advocated to relieve dyspeptic symptoms, suggesting that it may alter gastric motility via gastric distension. This study aimed to determine the effect of carbonated water on gastric emptying of a radiolabeled mixed meal in eight healthy volunteers. Meal emptying and its distribution within the stomach were assessed with carbonated and still water in a crossover study. Emptying of both solid and liquid, including the duration of the lag phase, was identical for both drinks. However, the proximal stomach contained a greater proportion of solids (74 +/- 7% vs 56 +/- 8%, P < 0.05) and liquids (43 +/- 5% vs 27 +/- 4%, P < 0.05) with carbonated water as opposed to still water. Retention of the meal within the proximal stomach ended with the lag phase and was likely related to proximal distension. In conclusion, carbonated water did not alter overall gastric emptying but profoundly modified intragastric distribution of the meal.

https://www.ncbi.nlm.nih.gov/pubmed/9009113

The proximal stomach is the part of the stomach that is closer to the lower esophageal sphincter, which is where acid reflux from the stomach occurs. If carbonated water causes the proximal stomach to contain more food and liquid than usual, that seems like it would contribute to acid reflux. I'll have to look more into it in the future.

In the meantime, when in (nauseated) doubt, set it out. The soda pop, that is.

Wednesday, September 28, 2016

Hold the condiments, please! (even if I really want them...)

I love condiments. A lovely sausage smothered in ketchup and mustard is a treat.

However, if a person has slow stomach emptying, they should probably steer clear of many condiments, marinades, and salad dressings due to the vinegar they contain:

Abstract Background: Previous studies on healthy people show that vinegar delays gastric emptying and lowers postprandial blood glucose and insulin levels. The aim of this study was to investigate the effect of apple cider vinegar on delayed gastric emptying rate on diabetes mellitus patients.
Methods: Ten patients with type 1 diabetes and diabetic gastroparesis, including one patient who had undergone vagotomy, were included and completed the investigator blinded crossover trial. The gastric emptying rate (GER) was measured using standardized real-time ultrasonography. The GER was calculated as the percentage change in the antral cross-sectional area 15 and 90 minutes after ingestion of 300 g rice pudding and 200 ml water (GER1), or 300 g rice pudding and 200 ml water with 30 ml apple cider vinegar (GER2). The subjects drank 200 ml water daily before breakfast one week before the measurement of GER1. The same subjects drank 200 ml water with 30 ml vinegar daily before breakfast for two weeks before the measurement of GER2.
Results: The median values of GER1 and GER2 were 27% and 17%, respectively. The effect of vinegar on the rate of gastric emptying was statistically significant (p < 0.05).
Conclusion: This study shows that vinegar affects insulin-dependent diabetes mellitus patients with diabetic gastroparesis by reducing the gastric emptying rate even further, and this might be a disadvantage regarding to their glycaemic control.

http://bmcgastroenterol.biomedcentral.com/articles/10.1186/1471-230X-7-46

If I'm fortunate enough to become pregnant again, I'll know now to avoid vinegar-containing condiments when experiencing symptoms of delayed stomach emptying. But otherwise, send that yummy BBQ sauce my way!

Tuesday, September 27, 2016

Why morning sickness is linked to a reduced chance of miscarriage

Yesterday, a new study was published in JAMA Internal Medicine in which they found a clear link between a woman having NVP (i.e., "morning sickness") and a lower chance of miscarriage:

Results A total of 797 women (mean [SD] age, 28.7 [4.6] years) had an hCG-confirmed pregnancy. Of these, 188 pregnancies (23.6%) ended in loss. At gestational week 2, 73 of 409 women (17.8%) reported nausea without vomiting and 11 of 409 women (2.7%), nausea with vomiting. By week 8, the proportions increased to 254 of 443 women (57.3%) and 118 of 443 women (26.6%), respectively. Hazard ratios (HRs) for nausea (0.50; 95% CI, 0.32-0.80) and nausea with vomiting (0.25; 95% CI, 0.12-0.51) were inversely associated with pregnancy loss. The associations of nausea (HR, 0.59; 95% CI, 0.29-1.20) and nausea with vomiting (HR, 0.51; 95% CI, 0.11-2.25) were similar for peri-implantation losses but were not statistically significant. Nausea (HR, 0.44; 95% CI, 0.26-0.74) and nausea with vomiting (HR, 0.20; 95% CI, 0.09-0.44) were associated with a reduced risk for clinical pregnancy loss.Conclusions and Relevance  Among women with 1 or 2 prior pregnancy losses, nausea and vomiting were common very early in pregnancy and were associated with a reduced risk for pregnancy loss. These findings overcome prior analytic and design limitations and represent the most definitive data available to date indicating the protective association of nausea and vomiting in early pregnancy and the risk for pregnancy loss.
http://archinte.jamanetwork.com/article.aspx?articleid=2553283

Why does morning sickness go along with a pregnancy that is less likely to miscarry? I think it is because a lack of hydrogen sulfide, which is necessary to good placental blood vessel development as mentioned in yesterday's post, causes a lower level of toxic sulfite--a hydrogen sulfide product--in the abdomen. An accumulation of sulfite is irritating to mucosal lining in the gastrointestinal tract, thus bringing on nausea and vomiting. Therefore, a pregnancy that isn't developing well is less likely to bring on NVP.

Does that mean that a woman without NVP needs to be frightened that she'll miscarry? The answer to that depends on how good her body is at breaking down sulfite. If she is making enough hydrogen sulfide for a healthy pregnancy but is also breaking down the resulting sulfite quickly, then she will likely have little or no NVP. But if her body is not making enough hydrogen sulfide, that would appear to be a bad portent for the pregnancy's outcome.

For more information on this theory, please see my YouTube video at https://www.youtube.com/watch?v=TaweHPbUPL0.

Monday, September 26, 2016

Common vetch and phocomelia

Phocomelia is "a rare congenital deformity in which the hands or feet are attached close to the trunk, the limbs being grossly underdeveloped or absent. This condition was a side effect of the drug thalidomide taken during early pregnancy," per the Oxford Dictionaries (https://en.oxforddictionaries.com/definition/phocomelia). Thalidomide was used in the 1950's and 1960's to alleviate pregnancy nausea, but its horrible effects on babies led to its being abandoned.

Thalidomide is in use again as a cancer drug. It is now known that its main mechanism of action is to interfere with angiogenesis, the creation of new blood vessels from existing blood vessels (https://www.ncbi.nlm.nih.gov/pubmed/7513432). Endogenous hydrogen sulfide (H2S) is an important part of angiogenesis, and inhibiting H2S-synthesizing enzymes negatively affects angiogenic processes (https://www.ncbi.nlm.nih.gov/pubmed/27569706).

Beta-cyanoalanine is a known inhibitor of two H2S-synthesizing enzymes, and it is found in common vetch (vicia sativa), a forage crop that is only suitable for consumption by animals with multiple stomachs (https://www.ncbi.nlm.nih.gov/pubmed/12055021). However, dried split common vetch seeds resemble light red lentils and sometimes find their way into the human diet. Australia had a scandal back at the end of the 20th century where common vetch was being coated in vegetable oil to darken it and passed off as "orange lentils" to consumers (http://www.abc.net.au/radionational/programs/healthreport/vetch-scandal/3565992); some people were also sneaking common vetch from Australia into the food supply of countries such as Bangladesh and India.

An epidemiologic survey of phocomelia incidence (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427055/) found that the highest prevalence (out of areas that recorded it) was in southern Australia during the time period 1983-2000 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427055/table/T2/). Other areas with similar reported phocomelia rates were in Italy, Slovakia, and eastern Germany (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427055/figure/F2/), all areas where common vetch is grown (http://www.cabi.org/isc/datasheet/56369).

India consumes a large amount of both red lentils (i.e., masoor dal) and common vetch, the latter which is supposed to be used only for animal feed, but due to financial issues, carelessness, and greed, it would be easy for common vetch to end up in the bowl of an impoverished pregnant woman. India suffers under a shortage of adequate medical personnel and resources, but doctors there are still identifying cases of non-thalidomide phocomelia. Two such cases were reported out of northern India in a February 2016 article: http://www.transbiomedicine.com/translational-biomedicine/nonsyndromic-phocomelia-a-case-series.php?aid=8794.

This evidence I have found and summarized above points to the possibility that common vetch is an overlooked angiogenesis disruptor that is behind some cases of unexplained phocomelia. I hope that someone with more resources than I can carry this investigation further.

Saturday, September 24, 2016

Possible new lead on phocomelia

While researching preterm birth today, I came across a lead on phocomelia, the limb malformation most known in connection with thalidomide. Phocomelia is still seen sometimes, as reported in this worldwide epidemiologic survey: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427055/.

A surgeon in India reported two non-thalidomide cases of phocomelia this past winter, and India is just the place I would have expected phocomelia cases to turn up in fairly regularly (I'll explain why in a later post). As I'm merely a researcher with no funding, I emailed the surgeon about the possible cause for phocomelia that I'd come across. He emailed back saying that unfortunately, he 1) is grossly overworked (I believe the numbers were roughly 2 surgeons for 100,000 people, which is at best quarter staffing per http://www.merritthawkins.com/pdf/a-review-of-physician-to-population-ratios.pdf) and 2) has no funding to do research or pay to have it published.

I did also email my phocomelia hypothesis to the corresponding author on the epidemiologic survey I mentioned above. Maybe she'll have the inclination and resources to pursue it. I'll write an explanation of the new lead next week here on the blog.

Friday, September 23, 2016

Citric acid and gastric emptying

Here's a short post on citric acid. It's not relevant to my family, for no one in this household has slow stomach emptying, but maybe some readers will be interested. If you want your stomach to empty quickly, citric acid consumption seems counterproductive. Here are a couple study abstracts relating to this:

 2006 Feb 3;308(1-2):8-13. Epub 2005 Dec 9.
The use of citric acid to prolong the in vivo gastro-retention of a floating dosage form in the fasted state.
Stops F1Fell JTCollett JHMartini LGSharma HLSmith AM.Abstract
Gastro-retentive dosage forms have the potential to improve local therapy and decrease the variation in bioavailability that is observed with a number of commercially available immediate and modified release preparations. In this study, a dosage form has been developed, utilising freeze-dried calcium alginate beads, designed to float on the surface of the stomach contents thus prolonging the retention time. The aim of the study was to also assess the in vivo behaviour of the radio-labelled calcium alginate beads when they were administered under fasting conditions with either water or an aqueous solution of citric acid, a potential gut transit delaying substance. The study was performed in healthy male volunteers who swallowed the radio-labelled calcium alginate beads after a 10h overnight fast. Gamma scintigraphy was selected as the method to monitor the movement of the calcium alginate beads. The volunteers consumed no further food or drink until gastric emptying of the calcium alginate beads was complete. The results indicated that prolonged gastric retention was achieved when the dosage form was administered with the citric acid solution when compared to retention in the absence of citric acid. Citric acid, therefore, has the potential to delay the gastric emptying of the calcium alginate beads when administered to fasted volunteers.
 1999 Aug;13(8):1057-62.

Citric acid or orange juice for the 13C-urea breath test: the impact of pH and gastric emptying.

Abstract

BACKGROUND:

There is an ongoing debate about the optimal test drink to be used in the 13C-urea breath test (13C-UBT). We recently reported that a citric acid solution is the optimal test drink in the 13C-UBT, because it provides a high 13CO2 recovery and the excellent accuracy of the test appears optimal compared to other test meals. Orange juice, because of a better taste, is also propagated as a test drink in the 13C-UBT.

AIM:

To compare the diagnostic accuracy of the 13C-UBT with either orange juice or citric acid solution as a test drink. Furthermore, the effect of these test drinks on the gastric emptying rate was determined.

METHODS:

H. pylori status was assessed by histology, rapid urease test and culture in 50 consecutive dyspeptic patients. A 13C-UBT was performed on two consecutive days by giving 75 mg of 13C-urea randomly dissolved in 200 mL 0.1 M citric acid solution or 200 mL orange juice. The 13CO2/12CO2 ratio was measured in breath samples taken before and 15, 30, 45 and 60 min after administration of the test drink. The gastric emptying rate of orange juice and citric acid solution was compared to that of water in 10 healthy subjects on three consecutive days by means of a 13C-sodium acetate breath test; 50 mg of 13C-sodium acetate was dissolved in 200 mL of each solution and breath samples were collected before and every 10 min for 90 min after administration of the test drink.

RESULTS:

Twenty-six out of 50 patients (52%) were infected with H. pylori. Significantly higher values over baseline (35.7+/-5.2 per thousand vs. 23.2+/-3.4 per thousand, P < 0.001) and higher area under the curve (1507+/-198 vs. 927+/-128, P < 0.001) were observed in H. pylori-positive patients when citric acid solution was administered compared with orange juice. Sensitivity of the 13C-UBT was 100% when citric acid was used as a test drink and 88% with orange juice. Specificity was 100% with both test drinks. Gastric emptying of citric acid solution (t1/2 = 60.9+/-3.5 min) was significantly slower than that of orange juice (t1/2 = 49.7+/-3.1 min, P < 0.001).

CONCLUSION:

13C-UBT loses diagnostic accuracy when orange juice instead of citric acid is used as a test drink. The faster gastric emptying of orange juice might be responsible for the lower diagnostic accuracy of the 13C-UBT.

Thursday, September 22, 2016

Low-dose aspirin for all pregnant women?

The American Journal of Obstetrics and Gynecology just printed an article arguing that it is probably beneficial to recommend that all pregnant women take low-dose aspirin in the first trimester in order to head off pre-eclampsia. Here's the abstract:

Low-dose aspirin has been demonstrated to reduce the incidence of pre-eclampsia and fetal growth restriction (FGR) in at-risk populations. Its’ role in low-risk populations is as yet unknown. Novel pre-eclampsia screening tests are emerging which can predict the risk of developing pre-eclampsia from as early as 11-weeks’ gestation. It may be more efficacious, acceptable and cost effective to prescribe low dose aspirin to all pregnant women from the first trimester as opposed to performing a screening test in the first instance. There is variation in opinion; the American College of Obstetricians and Gynecologists suggest use of aspirin only in women at risk of pre-eclampsia based on history taking, while the National Institute for Health and Clinical Excellence, UK and the U.S. Preventative Services Task Force recommend use if there is one major or two moderate risk factors. This point-counterpoint discussion shall address; (i) controversies regarding the real impact of low dose aspirin; (ii) controversies in the actual guidelines amongst the different national societies; (iii) controversies regarding emerging pre-eclampsia screening tests in terms of cost-effectiveness and efficacy and (iv) points in favour of the provision of universal versus screened-positive women.

http://www.sciencedirect.com/science/article/pii/S0002937816308043

Isn't this a bit premature considering we still don't know why preeclampsia happens? The first trimester is such an important time in fetal development, and even low-dose aspirin use can cause side effects like upset stomach, heartburn, and even stomach bleeding (just what a pregnant woman wants--morning sickness with blood in the vomit). Moreover, wouldn't it be safer and healthier to recommend pregnant women eat more foods with naturally occurring salicylates? (Here's a compilation of such foods - http://www.millhousemedical.co.nz/files/docs/factsheet_8_salicylates_in_foods.pdf.) Peppermint tea is high in salicylates, which is convenient for first trimester mothers, for peppermint oil also helps speed up gastric emptying, per https://www.ncbi.nlm.nih.gov/pubmed/17653649. By utilizing high-salicylate foods in place of aspirin, we avoid the corrosive acetic acid from aspirin, which decomposes into acetic acid and salicylic acids, per Wikipedia.

Wednesday, September 21, 2016

Stomach bug relief, starring molybdenum

Back when I was waiting on a decision whether Medical Hypotheses would publish my medical hypothesis on sulfite, molybdenum, and morning sickness, my sister and I tried out molybdenum to get rid of nausea in connection with stomach bugs. And it worked. 

But why? I didn't know, so I didn't dig into it. However, life with young children tends to provide repeated opportunities to ponder there wherefores of gastroenteritis, and I've just had a couple of days to do that. About 3-4 days ago, my four year-old daughter had diarrhea despite not having any vomiting beforehand. I wondered briefly if she had just had a stomach bug go through her, but since I didn't know of any contacts of hers having stomach bugs, I stopped worrying about it. 

Then yesterday, the two-year-old I babysit most afternoons couldn't come over because she had vomited. And it turned out that she had vomited five days ago, too. Out came the molybdenum for my whole family, for seven people in one household taking their turn vomiting is a nightmare I'd rather avoid. I've had intestinal gurgling for the past 24 hours, but no vomiting or nausea, and so far, no one else in the family has shown any signs of illness. The rest of the two-year-old friend's family hasn't been affected; her mom says that she made a barley (a very good source of molybdenum) soup for the family this past week that the two-year-old did not eat.

So, again, I'm wondering what is going on. Can molybdenum really get rid of nausea from gastroenteritis? Has it been overlooked as a nausea help because it tends to be mostly in foods that are difficult for an upset stomach to handle due to their lipid and fiber content? Barley water has been used as a traditional remedy for many things, including nausea, but it doesn't seem that anyone knew which components of barley helped with which ailments.

In the past decade, much research has been done on endogenous hydrogen sulfide (H2S), a catabolite of which is sulfite. It appears that H2S is part of the body's response to defend against inflammatory damage in the gastrointestinal tract:

Gastric mucosa expresses both CSE and CBS, which have the ability to mediate H2S synthesis (Fiorucci et al., 2005). In the gastrointestinal tract (GI), recent studies suggest that H2S may contribute to mucosal defense against injury caused by nonsteroidal anti-inflammatory drugs, and it also seems to play a significant role in regulating gastric mucosal blood flow. The mechanisms through which H2S exerts these anti-inflammatory properties are not fully understood. However, the involvement of ATP-sensitive potassium (KATP) channels must be considered (Fiorucci et al., 2006), because it was already demonstrated that H2S reduces leukocyte infiltration and edema formation via KATP channel activation (Zanardo et al., 2006). In contrast, Wallace et al. (2007) demonstrated that H2S promotes healing of gastric ulcers in rats by a mechanism that is not associated with KATPchannels, because neither glibenclamide (KATP channel antagonist) nor pinacidil (KATP channel activator) affected ulcer healing.

Our results confirmed that ethanol administration at high concentrations caused severe macroscopic and microscopic gastric mucosal damage, with hemorrhage, edema, and epithelial cell loss (Guslandi, 1987Laine and Weinstein, 1988;Medeiros et al., 2008). In the present study, we observed that both H2S donor and H2S precursor (L-cysteine) decreased ethanol-induced gastropathy. This effect was greatest after 30 min, persisted for 6 h, but was reversed 24 h after the H2S donor treatment. Furthermore, propargylglycine (an irreversible inhibitor of CSE) pretreatment prevented the protective effect of L-cysteine on ethanol-induced gastric damage. These findings are consistent with the hypothesis that gastroprotective effects of L-cysteine are correlated to increased H2S synthesis. Therefore, we could infer that H2S synthesis is essential to gastric protection against ethanol.


As part of our bodies' protection mechanisms from attack by the various viruses, bacterias, and parasites that we occasionally ingest, we might be increasing the amount of H2S in our stomach and intestines. If we are deficient in molybdenum, we will be deficient in the molybdoenzyme sulfite oxidase, which catalyzes the conversion of sulfite to sulfate; consequently, catabolism of hydrogen sulfide will be stopped at sulfite, which can lead to nausea and vomiting as our bodies try to expel the sulfite accumulating in the stomach and proximal intestine (as discussed...ad nauseum...in previous posts). Thus, in order to lessen nausea and vomiting in connection with stomach bugs, molybdenum supplementation should be an effective aid, preferably taken before the vomiting gets started, as absorption of any oral remedy is harder once vomiting has begun.

Does anyone out there know a cruise director, school nurse, or sleep-away camp director looking for a way to avoid a norovirus plague ruining their events? Send them my way, and I'll sing the praises of molybdenum to them. And when they look at me skeptically and ask, "Why haven't I heard of this being used as a nausea remedy before?", I will answer with another question, "Can you even pronounce molybdenum?" Outside the mining and metallurgy industries, few have paid more than passing attention to molybdenum until now, but I suspect recent findings on endogenous hydrogen sulfide will change that.

Tuesday, September 20, 2016

Sulfite oxidase in the stomach and chloride

The pH of the stomach is low, or acidic, ranging from 1-5. This is important because where the pH is less than 7, the enzyme sulfite oxidase is slightly different from high pH sulfite oxidase, i.e., where pH is higher than 9. The low pH form of sulfite oxidase can become blocked when there is not enough chloride. Here is a 2010 research report discussing this:
Abstract
The Mo(V) state of the molybdoenzyme sulfite oxidase (SO) is paramagnetic and can be studied by electron paramagnetic resonance (EPR) spectroscopy. Vertebrate SO at pH < 7 and pH > 9 exhibits characteristic EPR spectra that correspond to two structurally different forms of the Mo(V) active center referred to as the low-pH (lpH) and high-pH (hpH) forms, respectively. Both EPR forms have an exchangeable equatorial OH ligand, but its orientation in the two forms is different. It has been hypothesized that the formation of the lpH species is dependent upon the presence of chloride. In this work we have prepared and purified samples of wild type and various mutants of human SO that are depleted in chloride. These samples do not exhibit the typical lpH EPR spectrum at low pH, but rather show spectra that are characteristic of the blocked species that contains an exchangeable equatorial sulfate ligand. Addition of chloride to these samples results in the disappearance of the blocked species and the formation of the lpH species. Similarly, if chloride is added before sulfite, the lpH species is formed instead of the blocked one. Qualitatively similar results were observed for samples of sulfite oxidizing enzymes from other organisms that were previously reported to form a blocked species at low pH. However, the depletion of chloride has no effect upon the formation of the hpH species.
http://europepmc.org/articles/PMC2890295

Therefore, to have properly functioning sulfite oxidase in the stomach, it seems that we need chloride, or Cl-, there. (Note: this is not the chlorine that you think of as bleach or for use in water disinfection. That chlorine is Cl2.) Fortunately, we usually have plenty of chloride in our stomachs because of the hydrochloric acid (HCl) that is the main acid in our gastric juice. But during pregnancy we don't have enough hydrochloric acid in our stomachs. Per this study from 1936, almost no pregnant woman has normal levels of hydrochloric acid in her stomach by the end of pregnancy:

Gastric analyses.-Analyses were made upon 115 cases, 60 ante- and 55 post-partum. In the first trimester, 51 per cent of the cases showed normal gastric acidity; 40 per cent had hypochlorhydria, and 9 per cent achloryhdria. In the second trimester, 13 per cent showed hypochlorhydria and 87 per cent showed achlorhydria; in the third trimester, 0.5 per cent showed normal acidity, 3.5 per cent hypochlorhydria, and 96 per cent achlorhydria. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1561660/pdf/canmedaj00514-0104.pdf

Hypochlorhydria is low hydrochloric acid in gastric secretions; achlorhydria is the absence of hydrochloric acid in gastric secretions. Hypochlorhydria was found to be significantly associated with dyspepsia (i.e., heartburn, nausea, belching, upper abdominal pain) in females per a 2013 study (https://www.ncbi.nlm.nih.gov/pubmed/22829345). This gestational lack of hydrochloric acid fits well with the very common (up to 80%, per https://www.ncbi.nlm.nih.gov/pubmed/18843742) experience of heartburn during the third trimester of pregnancy.

But back to sulfite oxidase. As discussed many times previously, we want it functioning properly to break down sulfite in the stomach and upper intestine. So we need chloride in the stomach. If the gastric secretions don't include enough chloride during pregnancy, we need to look for other sources of chloride.

I started looking into chloride because one blogger said that switching from her prescription prenatal to Vitafusion Prenatal Gummy Vitamins made her morning sickness nausea go away (although she still wishes for a way to cure her acid reflux, i.e., heartburn). If the prescription prenatal vitamin had iron in it, I can see how switching to a iron-free gummy vitamin instead would make her feel better. Discontinuing iron-containing prenatal vitamins has been shown to improve nausea and vomiting in pregnancy (https://www.ncbi.nlm.nih.gov/pubmed/19280488).

But maybe there is something else in the Vitafusion gummies that is actually helping her. The ingredient list for the Vitafusion gummy vitamins looks fairly standard for prenatal vitamins except for one ingredient: choline chloride, a compound of choline and chloride. Perhaps she already has hypochlorhydria at her present stage of pregnancy and so the low pH form of sulfite oxidase in her stomach is being blocked due to chloride depletion; if that is the case, then by taking a compound with supplemental chloride in it, she helped unblock the sulfite oxidase and thus facilitated the enzyme's carrying out its normal activity.

If chloride ingestion can lead to faster conversion of sulfite to sulfate, that could explain why salty foods and drinks--Saltines, potato chips, french fries, Gatorade, etc.--often help women with morning sickness feel better. Salt is a very good source of Cl-.

Is dairy a good source of molybdenum?

Milk does contain molybdenum, but it appears to be mostly contained in the cream, per this 1951 study:

Molybdenum appears to be a natural constituent of cows’ milk, the amount varying in different individuals but of the general order of 40 to 70 γ per liter of whole milk.
Feeding 500 mg. daily of ammonium molybdate to eight cows for periods of 2 mo. increased the average amount of molybdenum in their milk about fivefold.
The level of molybdenum in these milks was higher than that of manganese and much higher than the level of cobalt. The response to feeding a supplement of the element, as indicated by increased levels in the milk, was greater than for any other trace element studied thus far.
Milk samples from control cows milked directly into glass showed similar levels of molybdenum as those obtained via the milking machine, thus eliminating the possibility that any of the molybdenum in the milks was due to metallic contamination.
Analysis of composite samples of cream and skimmilk showed that most of the molybdenum in “control” milks or in those from cows receiving a molybdenum supplement was concentrated in the cream fraction.
http://www.journalofdairyscience.org/article/S0022-0302(51)91818-8/abstract

So skim milk, nonfat yogurt, and ice milk are not going to be particularly good sources of molybdenum. Unfortunately, the slow stomach of a pregnant woman often doesn't respond well to large amounts of fatty food. Plus, some women experience aversion to milk during pregnancy.

So the answer to the question above seems to be that cream is a good source of dietary molybdenum if you can handle the smell and taste and keep it down afterward.

Monday, September 19, 2016

Scratch animation coming soon!

My nine year-old daughter has decided to help me make videos explaining my various hypotheses. She started already with one explaining the sulfite-molybdenum theory of morning sickness. It begins with a long-haired cat making retching noises as a wide stream of green comes out of her mouth. And the vomiting sounds go on for a while. I'm laughing just thinking of it. I'm going to need to put a trigger warning on the video for anyone who is already nauseated!

Saturday, September 17, 2016

New narrated video about sulfite-molybdenum theory of nausea and vomiting in pregnancy

I just posted a narrated slideshow about my sulfite-molybdenum theory of nausea and vomiting in pregnancy. You can view it here or at this link: https://youtu.be/TaweHPbUPL0


Friday, September 16, 2016

Why does ginger (sometimes) help with nausea?

There's a reason that ginger is so frequently recommended to people (especially pregnant ladies) suffering from nausea--it often works. Not much, but some, per this review published in 2014:
Twelve [randomized controlled trials] involving 1278 pregnant women were included. Ginger significantly improved the symptoms of nausea when compared to placebo (MD 1.20, 95% CI 0.56-1.84, p = 0.0002, I² = 0%). Ginger did not significantly reduce the number of vomiting episodes during NVP, when compared to placebo, although there was a trend towards improvement (MD 0.72, 95% CI -0.03-1.46, p = 0.06, I² = 71%). Subgroup analyses seemed to favor the lower daily dosage of <1500 mg="" nbsp="" span="">ginger for nausea relief. Ginger did not pose a significant risk for spontaneous abortion compared to placebo (RR 3.14, 95% CI 0.65-15.11, p = 0.15; I² = 0%), or to vitamin B₆ (RR 0.49, 95% CI 0.17-1.42, p = 0.19, I² = 40%). Similarly, ginger did not pose a significant risk for the side-effects of heartburn or drowsiness.
https://www.ncbi.nlm.nih.gov/pubmed/24642205

Ginger only helped me a little when I was pregnant, but it did seem to help. Maybe it was the placebo effect, maybe not. Unfortunately, now I associate ginger with pregnancy nausea, so I feel grossed out when I see the ginger pregnancy teas still floating around in my spice drawer.

On my last YouTube video, a woman commented that a peppermint and lemon tea helped get rid of her morning sickness. It turns out that peppermint oil speeds up gastric emptying (https://www.ncbi.nlm.nih.gov/pubmed/17653649), which as discussed in the previous post, appears to be delayed during pregnancy. In fact, HCG inhibits gastric emptying (https://www.ncbi.nlm.nih.gov/pubmed/23197744). If sulfite is building up in the stomach and bringing on nausea, emptying the stomach faster is a good way to get rid of the sulfite and the accompanying nausea.

And guess what else can speed up gastric emptying? Ginger. (https://www.ncbi.nlm.nih.gov/pubmed/11876024)

Which leaves me wondering why doesn't ginger help everyone with nausea? Is it because too much sulfite is just too much even if gastric emptying is sped up? Is it because sulfite in large amounts irritates the upper small intestine in a way that causes nausea, too? When we vomit, we don't just expel the contents of our stomach but also sometimes the proximal small intestine.

Thursday, September 15, 2016

Pregnancy-induced gastroparesis and molybdenum-containing foods

In the paper on my theory about sulfite accumulation being linked to "morning sickness," I mention that endogenous hydrogen sulfide not only keeps uterine muscles from contracting, but also might be responsible for relaxing and slowing down muscles in the gastrointestinal tract.

There is a medical disorder called "gastroparesis" that basically means the stomach empties slowly. Its symptoms are very similar to typical "morning sickness" symptoms; they include heartburn, bloating, nausea, vomiting, and feeling full too soon. For severe cases of gastroparesis, the short-term recommended diet is saltine crackers, Gatorade, and bouillon. Sound familiar? Saltines and Gatorade are common diet recommendations for "morning sickness" sufferers. I think that morning sickness is probably pregnancy-induced gastroparesis.

Unfortunately, the longer-term diet recommendations for gastroparesis specifically exclude pulses, whole grains, nuts, milk cream, and green fibrous vegetables. Guess what? Those are the foods that are high in molybdenum. So if a pregnant woman, in trying to not suffer from her slowed-down stomach and small intestine, eats a gastroparesis-friendly diet, she's is almost certainly going to become deficient in molybdenum. And if she is deficient in molybdenum, then she will suffer from sulfite accumulation in her abdomen. No wonder women suffer so much from "morning sickness." The foods that have the molybdenum they need are far less palatable during pregnancy. It seems that women with slow stomach emptying during pregnancy can best keep their molybdenum levels up by 1) taking vitamins with molybdenum and 2) sipping barley water (it is less "bulky" than oat water but still has high molybdenum content).

This is a bit of a jump, but perhaps gastroparesis sufferers would have less nausea if they increased their molybdenum intake. Are there any gastroparesis sufferers out there who have tried molybdenum supplements and seen any difference in their symptoms? If so, please comment and share your experience.

Wednesday, September 14, 2016

And trying out Twitter

I finally joined Twitter. Here's my account: https://twitter.com/CT_NutritionRes

I don't have a smart phone, so I'm not the typical Twit. Oh, that's not what Twitter users are called? ;)

I tweeted the link to the slideshow I posted on YouTube a couple of days ago, and I'm trying to get the word out on molybdenum/sulfite issues by replying to recent tweets about morning sickness. It seems selfish to have an overlooked help for morning sickness and not make an effort to publicize it. It's not controversial to promote consumption of molybdenum, for it's a trace mineral in many foods and is essential to good health. But I admit it's hard to pronounce the element's name. It took me a couple of weeks to have "molybdenum" finally roll off my tongue properly.

Monday, September 12, 2016

Nitrite can be a substrate of sulfite oxidase, too

Last week I came across this 2015 paper, wherein the authors report their discovery that sulfite is not the only substrate of the enzyme sulfite oxidase (that's the enzyme which according to my hypotheses is overwhelmed in situations of "morning sickness" and migraine headaches). Under hypoxic circumstances or when there is excessive sulfite, nitrite can be a substrate of sulfite oxidase. Here's the abstract:

Aims: Recent studies suggest that the molybdenum enzymes xanthine oxidase, aldehyde oxidase, and mARC exhibit nitrite reductase activity at low oxygen pressures. However, inhibition studies of xanthine oxidase in humans have failed to block nitrite-dependent changes in blood flow, leading to continued exploration for other candidate nitrite reductases. Another physiologically important molybdenum enzyme—sulfite oxidase (SO)—has not been extensively studied. Results: Using gas-phase nitric oxide (NO) detection and physiological concentrations of nitrite, SO functions as nitrite reductase in the presence of a one-electron donor, exhibiting redox coupling of substrate oxidation and nitrite reduction to form NO. With sulfite, the physiological substrate, SO only facilitates one turnover of nitrite reduction. Studies with recombinant heme and molybdenum domains of SO indicate that nitrite reduction occurs at the molybdenum center via coupled oxidation of Mo(IV) to Mo(V). Reaction rates of nitrite to NO decreased in the presence of a functional heme domain, mediated by steric and redox effects of this domain. Using knockdown of all molybdopterin enzymes and SO in fibroblasts isolated from patients with genetic deficiencies of molybdenum cofactor and SO, respectively, SO was found to significantly contribute to hypoxic nitrite signaling as demonstrated by activation of the canonical NO-sGC-cGMP pathway. Innovation: Nitrite binds to and is reduced at the molybdenum site of mammalian SO, which may be allosterically regulated by heme and molybdenum domain interactions, and contributes to the mammalian nitrate-nitrite-NO signaling pathway in human fibroblasts. Conclusion: SO is a putative mammalian nitrite reductase, catalyzing nitrite reduction at the Mo(IV) center. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523048/

What does this mean? It means that if sulfite accumulation contributes to migraine headaches and nausea and vomiting in pregnancy (NVP), one should not only avoid eating sulfites but nitrites, too, when trying to avoid migraines or alleviate NVP. That is because--if I'm correctly understanding the report's discussion of oxidation states of molybdenum--nitrite will further tie up sulfite oxidase and slow it down in its primary function of catalyzing the conversion of sulfite to sulfate. The result of sulfite oxidase's acting on nitrite is nitric oxide, and nitric oxide levels do appear to go up around the time of migraine headaches (https://www.ncbi.nlm.nih.gov/pubmed/17116218).

Considering that nitrites have been long seen as a trigger for migraines (http://permanent.access.gpo.gov/lps1609/www.fda.gov/fdac/features/1998/398_pain.html), this isn't a revolutionary diet change to suggest to migraine sufferers. However, I've never seen nitrites mentioned as something to avoid when pregnant; deli meat, certainly, but the reason given for the counsel to avoid deli meat during pregnancy is typically listeria (http://americanpregnancy.org/is-it-safe/deli-meats/).

Saturday, September 10, 2016

Taking it to YouTube

I am going to experiment with posting about my nutrition/biomedical hypotheses on YouTube. Here's my first upload:


I plan on making videos with sound and maybe even pictures, if my children want to help. After all, they hear about my research findings quite often.

Friday, September 9, 2016

More on sulfites and another color preserving food additive

Sulfiting agents used in food are collectively known as "sulfites." The FDA categorizes sulfites as "generally regarded as safe" ("GRAS"), although back when it was legal to use them on restaurant salad bars, where they used sulfites to keep cut fruits and vegetables looking fresh, sulfites used to be the cause of many trips to hospital emergency rooms with a wide variety of symptoms, including asthmatic attacks, nausea, abdominal pain, seizures, and even death (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1346296/). The University of Florida has a very good summary on the subject of sulfites at this site: http://edis.ifas.ufl.edu/fy731.

As discussed in my prior blog posts, the sulfite molecule appears to be connected to nausea and vomiting in pregnancy and to migraine headaches. Despite sulfiting agents not being allowed by the FDA on most fresh fruits and vegetables, it still shows up in on two commonly-eaten forms of produce: 1) frozen potato products and 2) grapes, on which it is used as a pesticide (against black widow spiders) and fungicide. It appears that organic grapes have much less in the way of sulfites, though, per this 2012 paper--http://www.sciencedirect.com/science/article/pii/S0925521411001633--which says that sulfur dioxide is not allowed as a fungicide on organic grapes.

Let's talk about potatoes for a minute. In May 2016, health news contained a surprising report that potato consumption had been linked to hypertension (high blood pressure) (http://well.blogs.nytimes.com/2016/05/17/potatoes-tied-to-high-blood-pressure-risk). This is especially confusing because back in 2012, a study looking specifically at purple potatoes found that eating them lowered blood pressure (https://www.ncbi.nlm.nih.gov/pubmed/22224463). But when one delves deeper into the finding of the 2016 news, one sees that they looked at consumption of 3 categories of potatoes: 1) baked/mashed/boiled, 2) French fries, and 3) potato chips.

In three prospective cohorts of US women and men, we found that higher long term intake of baked, boiled, or mashed potatoes was significantly associated with an increased risk of hypertension in women, independent of numerous other predictors of risk of hypertension including dietary factors such as whole grain intake and whole fruit and vegetable intake. In addition, higher consumption of French fries was associated with incident hypertension in all three cohorts, whereas potato chip intake was associated with no increased risk.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870381/

Did you see that? No increased risk with potato chip intake? Isn't that a head scratcher? What is in potato chips? Potatoes, salt, and lots of oil...but those same things are in French fries! How can potato chips not be linked to hypertension if the other two categories are? What is the difference between potato chips and the other two categories of potatoes? I submit that it is the absence of sulfites and other color preservers in potato chips that is the difference. French fries are permitted to have sulfites (although most fast food chains and frozen potato food manufacturers in the US now instead use disodium pyrophosphate, which is also considered GRAS by the FDA but might pose its own risks, which I'll partially address below) to keep them from turning brown, and mashed potatoes--the most popular choice out of "baked, boiled, and mashed" potatoes in my experience--are usually made from potato flakes that include sodium metabisulfite as a preservative. Potato chips, on the other hand, generally don't include color preserving additives because chip makers fry the chips almost immediately after slicing the potatoes. Here's a video on the process of making potato chips:


Earlier this year, it was noted in a cardiovascular medicine journal that recent findings of sulfites contributing to cardiac dysfunction "should raise a fundamental concern about sulfite preservatives used in wine industry or food" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880594/). An Iranian study published in 2014 found that ingestion of sodium metabisulfite by rats resulted in an average 43% decrease in heart capillary volume and length (https://www.ncbi.nlm.nih.gov/pubmed/25629268); that doesn't seem like it would be good for the heart or cardiac blood pressure.

As for disodium pyrophosphate, German researchers expressed strong concern in 2012 (https://www.ncbi.nlm.nih.gov/pubmed/22334826that phosphate food additives, including disodium pyrophosphate, possibly are increasing mortality in those with chronic kidney disease by causing vascular damage, e.g., vascular calcification and endothelial dysfunction. Vascular calcification is a major cause of systolic hypertension in the elderly (https://www.ncbi.nlm.nih.gov/pubmed/22713153), and isolated systolic hypertension appears to be an indicator of worse coronary function than combined systolic/diastolic hypertension (https://www.ncbi.nlm.nih.gov/pubmed/23205754).

I think that the humble potato was unfairly maligned back in May. If the potato itself caused hypertension, potato chip intake should have been associated with hypertension similarly to the other two categories of potato products. I'm still not ready to think of potato chips as "health food," but the evidence seems to excuse them as innocent of causing hypertension and instead points to the food additives being used to keep potatoes from browning.

As a result of research I've done this year--predominantly in peer-reviewed studies and not alarmist, supplement-selling websites--I am starting to lose faith in the FDA's "GRAS" label. Then again, maybe nearly any chemical in large quantities is just bad for us. Talking about moderation, balance, and avoidance of several known-but-popular-and-legal mind-altering substances is not very exciting, but the combination of these principles seems to be a boring, consistent key to maintaining good health.

Update: I just got back from grocery shopping for the family. I started reading labels, and it looks like the "fundamental concern about sulfite preservatives used in...food" expressed earlier this year (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880594/) was taken seriously. A few months ago, I recall all the non-organic tortillas containing sodium metabisulfite. Now most of the tortillas I looked at do not have sodium metabisulfite. They do still have an additive that, if I recall correctly, is disodium pyrophosphate. And I vaguely recall that a few months ago, I found frozen potato products with added sulfites, but those are all gone now; all the frozen potato products have disodium pyrophosphate in them. This was a quiet ingredient change and hopefully one for the better, as far as Americans' health. However, in light of what I found out today about vascular calcification resulting from too much phosphate (and it's much easier to absorb excessive phosphate from phosphate food additives), I am not unworried by the widespread use of disodium pyrophosphate. Can I please just have regular food to feed my family with?

Wednesday, September 7, 2016

Slideshow summarizing sulfite/molybdenum theory of "morning sickness"

Since $35 is a lot to pay to read my paper on how sulfite contributes to nausea and vomiting in pregnancy, I prepared a slideshow summarizing my theory. It also explains how molybdenum-rich foods and supplementation with molybdenum can help alleviate that nausea and vomiting. Here it is:


video