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Vitamin C and Pregnancy

What is a safe amount of vitamin C during pregnancy? In her keynote speech for 2017 LiveAware Expo (San Francisco, California), Suzanne Humphries, MD, discussed the medical literature that she was able to track down regarding supplemental vitamin C use during pregnancy. She had received multiple questions from women via email about safe dosage, rebound scurvy, and concerns that too much C might cause spontaneous abortion.

Guinea pig studies indicate that a newborn whose mother was on high-dose vitamin C supplementation during pregnancy can experience a rebound effect if supplementation is discontinued after birth. Like humans, guinea pigs do not produce vitamin C in their bodies. Pups whose mothers were given the human equivalent of 1500 mg/day throughout pregnancy developed scurvy after birth four days sooner than pups from mothers without supplementation (Norkus 1975, PMID 1060409). Pups whose mothers received supplementation during pregnancy metabolize ascorbic acid at a faster rate than those who do not (Norkus 1981, PMID 7218035), which explains why the pups from supplemented mothers developed signs of scurvy sooner. This evidence of "rebound scurvy," is one reason that people who take high doses of ascorbic acid for extended periods are advised to reduce the dose gradually rather than stopping abruptly.

The sole report about spontaneous abortion apparently originated with a Russian study that Humphries was in the process of acquiring at the time of her talk. That being said, Humphries referred to the 2015 Cochrane review on vitamin C use in pregnancy that reported "no convincing evidence" of harms (Rumbold 2015, PMID 26415762). Also, Rumbold et al found good evidence from eight high-quality studies that supplementation (1000 mg/day, according to Clemetson) produced 36% relative reduction in placenta abruption.

In addition to the Cochrane review, Frederick R. Klenner wrote about his use of high-dose vitamin C in 300 women (J Applied Nutrition, Winter 1971;23(3&4)). The women took about 4,000 mg/day (divided doses) in the first trimester, 6,000 mg/day in the second trimester, and 8,000-10,000 mg/day (with about 20% taking 15,000 mg) in the third trimester. Eighty percent of the women also received booster injections of 10,000 mg upon arriving at the hospital. No miscarriages occurred. In this study, Klenner said, "Observations made on over 300 consecutive obstetrical cases using supplemental ascorbic acid, by mouth, convinced me that failure to use this agent in sufficient amounts in pregnancy borders on malpractice." Humphries notes that Klenner undoubtedly made sure that the mothers continued to take vitamin C after delivery, avoiding any rebound effects for mother and breastfeeding infant.

Vitamin C is vital for the growth and repair of all tissue, as well as being an antioxidant and an anti-viral. The amniotic fluid contains three times the amount of C found in the mother's blood. The placenta after birth and cord blood have twice the maternal blood level. The stress of labor and vaginal delivery uses up a lot of this antioxidant. Babies often display jaundice due to high bilirubin levels after birth. Bilirubin, produced in the body, is also a strong antioxidant that neutralizes free radicals. Supplementation with vitamin C during pregnancy with 500 mg/day reduces the incidence of neonatal jaundice (Garbelli 1957, PMID 13420320).

Dr. Humphries advises women to "start slow and low" in order to learn their own tolerance for vitamin C supplementation. Women with type 1 diabetes or who smoke, use alcohol, and/or eat a lot of carbohydrates have a need for more vitamin C. Sugars--even from carbohydrates like sweet potatoes--compete with vitamin C's entry into cells. She encourages people to include high-vitamin-C food sources (i.e. red peppers, kiwi fruit, and parsley) in a diet of organic, low-processed foods. Humphries, board-certified in nephrology and internal medicine, recommends that people hydrate/drink water before taking vitamin C supplements to protect the kidneys. In other lectures, she reports finding little evidence that ascorbic acid or sodium ascorbate cause kidney stones but advises hydration to be on the safe side. Finally, she says to taper the dosage down, rather than stopping abruptly, to avoid rebound effects.

The Placenta

Although the placenta has been long recognized as a conduit for nutrition from mother to fetus, its role as a neuroendocrine organ and regulator of the fetus' environment and development is new territory. That conduit linking the mother's blood supply to the fetus' does not become active until about 10 weeks gestation, but placental cells have a major role in pregnancy success from the very beginning. With current molecular and imaging technologies, researchers are investigating placental changes in structure and function that occur throughout pregnancy. They are also looking at environmental factors that affect the placental epigenome, fetal development, and infant health. "Epigenetic studies are starting to show links between the placental epigenome and a number of infant health markers," says journalist Lindsey Konkel. "Variations in DNA methylation patterns in certain gene regions have been associated with infant birth weight, gestational age at birth, and neurobehavioral measure."

In early pregnancy, when major organs are beginning to develop, the placental cells secrete proteins and hormones such as human chorionic gondotropin (hCG). This hormone, which has several functions, tells the mother's ovaries to produce steroid hormones needed to maintain the pregnancy. hCG also stimulates testosterone production, which is needed for gender differentiation in the male fetus. Environmental exposures present in the mother's blood can affect the placenta's hormone signals. For example, Jennifer Adibi, a molecular biologist at the University of Pittsburgh, found that cultured placental cells exposed to phthalates (found in plastics) produced less hCG than non-exposed cells. Phthalates are commonly found in the blood of Americans.

The placentas for male and female fetuses appear to respond to environment stresses differently. In her laboratory research with mice, environmental scientist Cheryl Rosenfeld found that change in the mother's diet produced different placental DNA methylation and gene expression patterns according to gender. These placental changes were associated with gender-dependent responses to eating a high-fat diet after birth. The placental epigenome also responded to maternal stress according to gender; male offspring showed "maladaptive inflammatory and behavioral responses to stress as adults."

At this time, researchers are using embryonic stem cells converted into placental cells to identify environmental factors that affect early pregnancy. Human placentas delivered at term are also being studied. Researchers have not yet identified ways to follow the organ's changes in function and structure that occur throughout pregnancy. No animal models make a good surrogate for the human placenta. David Weinberg, a translational scientist at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, says, "'To really understand placental function and development, we need to be able to monitor it all across pregnancy.'" Weinberg heads the institute's Human Placenta Project (HPP), initiated in 2014. He and his colleagues are looking for non-invasive, realtime methods for assessing placental development, function, and response to environmental factors.

Fetal and Postnatal Metal Dysregulation

A recent twin study, conducted by Manish Arora and colleagues, found an association between prenatal and early postnatal exposure to neurotoxic metals, essential mineral deficiencies, and autism spectrum disorder (ASD). The researchers recruited 32 ASD-discordant twin pairs (one twin diagnosed with ASD and the other without ASD) enrolled in Sweden's Roots of Autism and ADHD Twin Study in Sweden (RATSS) from whom naturally shed deciduous teeth could be obtained; 17 were monozygotic pairs (MZ) and 15 were dizygotic (DZ) pairs. The authors used tooth-matrix biomarkers to assess uptake of ten elements from the second trimester to early childhood: barium, chromium, copper, lithium, magnesium, manganese, lead, tin, strontium, and zinc. Unlike earlier studies that used whole ground teeth (and found no correlation between ASD and metals), their technique uses a laser to slice the tooth from top to bottom to obtain time-series data samples for mass spectrometry analysis.

The researchers found different levels for six of the ten elements in twins with ASD compared to non-ASD twins. Manganese, zinc, and lead were the most significant. Manganese levels were lower and lead levels were higher (particularly after birth) in twins with ASD, compared to unaffected twins. The manganese difference was statistically significant for two periods: between 10 weeks prenatally and birth, and from week 5 to week 20 after birth. "The greatest difference was observed at postnatal week 15 when cases had 2.5 times lower manganese than their co-twins (Holm-Bonferroni 95% CI 1.1-4.5 times lower). Differences of a similar magnitude were also observed 7 weeks before birth." The zinc pattern was more complex, say the authors. Zinc levels declined around birth in non-ASD twins and earlier, during the prenatal period, for the twins with ASD. Zinc levels then markedly increased postnatally in the ASD twins, "surpassing the levels in their non-ASD co-twins." In addition, twins with ASD had higher tin and strontium levels and lower chromium levels.

The researchers correlated the tooth-matrix biomarkers with autism severity scores about a decade later, using Social Responsiveness Scale Second Edition (SRS-2) and Autism Diagnostic Observation Schedule Second Edition (ADOS-2). Lead was positively associated with scores from these assessments. Manganese concentrations were inversely associated with autistic traits with the strongest association at 15 weeks of age for SRS-2 and at 12 weeks for ADOS-2. None of the other tested elements showed a statistically significant association with the autistic trait measures

"Our findings along with other recent studies bolster the premise of joint interaction of environmental exposures with genetic variations in the etiology of ASD," say Arora et al. "Notably, many of the genes associated with ASD are also linked with elemental homeostasis, and it is intriguing that genes implicated in ASD converge to specific neuronal co-expression networks especially during the same critical early developmental periods we have observed in this study." They note that fetal zinc deficiency causes epigenetic alterations in gene coding for the metal transporter, metallothionein-2. The authors would like to see if larger non-twin studies support their findings. (It would also be interesting to measure for other elements, such as mercury and aluminum.)

As an aside...I was surprised by the significant association between manganese deficiency and ASD severity reported in this study. It brought to mind a recent review by pathologist James E. Beecham and MIT computer scientist Stephanie Seneff that suggests a correlation between the widespread use of glyphosate herbicides and increased incidence of ASD. Glyphosate chelates manganese ions. The manganese blood levels of cows given glyphosate-exposed feed were extremely low in a recent study. Beecham and Seneff explain that manganese deficiency interferes with the function of manganese-dependent enzymes, leading to a reduction in maternal serum levels of thyroid-stimulating hormone (TSH)--affecting mother and fetus.

Inhalation for Vaginismus and Pelvic Floor Pain

Erik Peper, PhD, and Tal Cohen say that relaxation of the pelvic floor muscles during inhalation is a key step for addressing involuntary perineal and paravaginal muscle contraction (vaginismus) that interferes with sexual intercourse and can cause pain (dyspareunia). Vaginismus is usually treated by sequential dilation of the vaginal opening with progressively larger cones, psychotherapy, and medication for anxiety and pain. The authors say, "The dilation is effective if the pelvic floor muscles are relaxed; however, the patient may not be aware whether the muscles are relaxed or contracted." In their article, they discuss the biological processes that contribute to vaginismus and dyspareunia.

Before engaging in sequential dilation exercises, the woman needs to learn how to use diaphragmatic breathing, relaxing the neck and shoulder muscles during exhalation and the pelvic floor muscles during inhalation. Biofeedback monitoring of the breathing pattern and lower abdominal muscle activity is helpful when learning to breathe effectively. "The pelvic floor descends and relaxes, especially when sitting up when you can even feel the anus slightly going down and widening," the authors explain. "This occurs during effortless abdominal breathing when one feels safe...." Fostering a sense of safety is important because fear or anticipation of pain causes the abdominal and pelvic floor muscles to contract in an attempt to protect the body's core.

Once the woman can sense pelvic floor relaxation, she is ready to begin dilation practice, with a lubricant, by inserting a very small-diameter dilator and progressing to a larger diameter. The authors advise pushing the dilator only during the midphase of inhalation. If pain arises, they say to relax the shoulders and simply breath until the pain subsides, then push very little on the next inhalation: "Go much slower and with more tenderness." Trying to stretch a muscle too quickly causes an automatic contraction response; this automatic stretch reflex is the body's method for preventing muscle damage from over-stretching.

"Be patient," Peper and Cohen write. "Explain to your partner that your body and mind need time to adjust to new feelings. However, don't stop having sex--you can have great sex without penetration. Practice both alone and with your partner; together find the best angle and rate. Use different lubricants to check out what is best for you." For more information, they recommend Dr. Lonnie Barbach's books For Each Other: Sharing Sexual Intimacy and For Yourself: The fulfillment of Female Sexuality.

Humphries S. Vitamin C and Pregnancy--Experience and the Medical Literature,

Konkel L. Lasting Impact of an Ephemeral Organ. Environmental Health Perspectives. July 2016;124(7):A124-A129.

Arora M et al. Fetal and postnatal metal dysregulation in autism. Nature Communications. June 1, 2017. Beecham JE, Seneff S. Is there a link between autism and glyphosate-formulated herbicides? 1 Autism. 2016;3(1).

Peper E, Cohen T. Inhale to Breathe Away Pelvic Floor Pain and Enjoy Intercourse. Biofeedback. Spring 2017;45(1):21-24.

briefed by Jule Klotter
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Title Annotation:vitamin C during pregnancy / placenta influences fetal development and health / austism spectrum disorder and prenatal neurotoxic metal exposure
Author:Klotter, Jule
Publication:Townsend Letter
Date:Feb 1, 2018
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