Folic acid supplements early in pregnancy may reduce child’s risk of autism by 40 percent

Large study in Norway finds early timing of supplements is critical:

JAMAPrenatal folic acid supplements appear to reduce the risk for autistic spectrum disorders, according to a study published today (February 13) in the Journal of the American Medical Association (JAMA).

The Centers for Disease Control and Prevention estimate that about 1 in 88 children in the U.S. have been identified with an Autism Spectrum Disorder (ASD). ASDs are amongst the most heritable of mental disorders, but little is known about how the disorder develops. Consequently, methods for diagnosis, prevention, and treatment are limited.

Folic acid (Vitamin B9) is required for DNA synthesis and repair in the human body, and its naturally occurring form—folate—is found in leafy vegetables, peas, lentils, beans, eggs, yeast, and liver. Taking folic acid supplements during early pregnancy is known to protect against spina bifida and other neural tube defects in children. In the United States, Canada, and Chile, folic acid is added to flour, so as to automatically provide these supplements to consumers. Norway does not enrich its flour, and since 1998, the Norwegian Directorate of Health has recommended that all women planning to become pregnant take a daily supplement of folic acid from one month before the start of pregnancy through the first trimester.

Despite this policy, studies from North America and Europe have shown that many pregnant women have a lower dietary intake of folate than what is necessary to prevent neural tube defects.

The report in JAMA emerged from the Norwegian Mother and Child Cohort Study (MoBa) and its sub-study of autism, the Autism Birth Cohort (ABC) Study. This international collaboration (see list of members below) comprises the largest prospective birth cohort devoted to the investigation of gene-environment interactions and biomarker discovery for neuropsychiatric disorders.

A total of 85,176 MoBa babies—born from 2002-2008—and their parents participated in the study. Prenatal dietary habits were recorded, and families were regularly surveyed for 3-10 years to measure the development of autism spectrum disorders. A total of 270 cases of autism spectrum disorders were identified in the study population (114 autistic disorder; 56 Asperger syndrome; 100 atypical or unspecified autism; i.e., pervasive developmental disorder not otherwise specified, PDD-NOS).

Mothers who took folic acid supplements in early pregnancy had a 40% reduced risk of having children with autistic disorder compared with mothers who did not take folic acid. The reduction in risk was observed in those who took folic acid during the time interval from 4 weeks before to 8 weeks after the start of pregnancy. Autistic disorder is the most severe form of autism spectrum disorders in children. No reduction in risk was observed for PDD-NOS. For Asperger syndrome, the number of children was too low to obtain sufficient statistical power in the analyses.

The use of folic acid in early pregnancy increased substantially from 2002 to 2008 among women who participated in MoBa. In 2002, 43% of mothers took folic acid supplements; by 2008, 85% of mothers did. However, many women began taking folic acid later than recommended, and only half started before the beginning of pregnancy.

The timing of a mother’s intake of folate appears to be a critical factor. Her child’s risk of autism was reduced only when the supplements were taken between 4 weeks before to 8 weeks after the start of pregnancy.

“We examined the rate of autism spectrum disorders in children born to mothers who did or did not take folic acid during pregnancy. There was a dramatic reduction in the risk of autistic disorder in children born to mothers who took folic acid supplements,” says Pål Surén, first author and epidemiologist at the Norwegian Institute of Public Health (NIPH).

The researchers also analyzed whether the risk of autistic disorder was influenced by the use of other dietary supplements. They did not find any association between the mother’s use of fish oil supplements (cod liver oil and omega-3 fatty acids) in early pregnancy and the risk of autistic disorder, and no association for the mother’s use of other vitamins and minerals.

In recent years, researchers have started to investigate whether folic acid has other beneficial effects on the development of the fetus’ brain and spinal cord. A study of language development from MoBa, published in 2011, showed that children whose mothers took folic acid supplements in early pregnancy had only half the risk of severe language delay at age three years compared with other children. A separate 2011 study from the University of California, Davis, demonstrated a lower risk of autism spectrum disorders in children of mothers who had used prenatal vitamin supplements during pregnancy. Prenatal vitamin supplements contain folic acid in combination with other vitamins and minerals.

Joint senior author Ezra Susser, professor of Epidemiology at Columbia University’s Mailman School of Public Health and professor of Psychiatry at the College of Physicians and Surgeons, stated, “Our findings extend earlier work on the significance of folate in brain development and raise the possibility of an important and inexpensive public health intervention for reducing the burden of autism spectrum disorders.”

“This elegant work illustrates the power of the ABC cohort for not only chipping away at the riddle of what causes autism, but for developing new methods for early recognition, prevention and treatment,” says W. Ian Lipkin, John Snow Professor of Epidemiology at the Mailman School of Public Health and principal investigator of the ABC cohort.

 

Reference

Surén P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie KK, Lipkin WI, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Smith GD, Øyen AS, Susser E, Stoltenberg C. Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in Children. JAMA 2013; 309 (6): 570-577.

 

Prenatal folic acid supplementation associated with lower risk of autism

JAMAIn a study that included approximately 85,000 Norwegian children, maternal use of supplemental folic acid from 4 weeks before to 8 weeks after the start of pregnancy was associated with a lower risk of autistic disorder in children, according to a study appearing in the February 13 issue of JAMA.

“Supplementation with folic acid around the time of conception reduces the risk of neural tube defects in children. This protective effect has led to mandatory fortification of flour with folic acid in several countries, and it is generally recommended that women planning to become pregnant take a daily supplement of folic acid starting 1 month before conception,” according to background information in the article. It has not been determined whether prenatal folic acid supplements protect against other neurodevelopmental disorders.

Pal Surén, M.D., M.P.H., of the Norwegian Institute of Public Health, Oslo, and colleagues investigated the association between the use of maternal folic acid supplements before and in early pregnancy and the subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children. The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (average age, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Analyses were adjusted for maternal education level, year of birth, and parity (the number of live-born children a woman has delivered).

A total of 270 children (0.32 percent) in the study sample have been diagnosed with ASDs: 114 (0.13 percent) with autistic disorder, 56 (0.07 percent) with Asperger syndrome, and 100 (0.12 percent) with PDD-NOS. The researchers found that there was an inverse association between folic acid use and subsequent risk of autistic disorder. Autistic disorder was present in 0.10 percent (64/61,042) of children whose mothers took folic acid, compared with 0.21 percent (50/24,134) in children whose mothers did not take folic acid, representing a 39 percent lower odds of autistic disorder in children of folic acid users.

Characteristics of women who used folic acid within the exposure interval included being more likely to have college- or university-level education, to have planned the pregnancy, to be nonsmokers, to have a pre-pregnancy body mass index below 25, and to be first-time mothers.

“No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use,” the authors write.

The researchers note that the inverse association found for folic acid use in early pregnancy was absent for folic acid use in mid pregnancy.

“Our main finding was that maternal use of folic acid supplements around the time of conception was associated with a lower risk of autistic disorder. This finding does not establish a causal relation between folic acid use and autistic disorder but provides a rationale for replicating the analyses in other study samples and further investigating genetic factors and other biological mechanisms that may explain the inverse association,” the authors conclude.

 

Reference

Surén P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie KK, Lipkin WI, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Smith GD, Øyen AS, Susser E, Stoltenberg C. Association Between Maternal Use of Folic Acid Supplements and Risk of Autism Spectrum Disorders in Children. JAMA 2013; 309 (6): 570-577.

 

A Diet High in Choline During Pregnancy May Mean Less Stress for Baby

New research from Cornell University indicates that pregnant women who increase choline intake in the third trimester of pregnancy may reduce the risk of the baby developing metabolic and chronic stress-related diseases like high blood pressure and diabetes later in life (1). The results, published in the latest edition of the Journal of the Federation of American Societies for Experimental Biology (The FASEB Journal), suggest that choline, a nutrient found in high quantities in eggs, may help protect against the effects of a mother’s stress during pregnancy (1).

Previous research indicates high exposure to the stress hormone cortisol during pregnancy, often due to maternal anxiety or depression, may make offspring vulnerable to stress-induced illness and chronic conditions (2, 3). This finding adds to the growing body of evidence demonstrating the importance of choline in fetal development.

A Closer Look at the Study

Twenty-four women in the third trimester of pregnancy were randomly assigned to consume either 480 milligrams (mg) choline per day or 930 mg per day for 12 weeks prior to delivery. Researchers collected maternal and placental blood samples as well as samples of placental tissue. They then compared cortisol levels and genetic differences among all the samples. The researchers observed lower levels of cortisol in the placental cord and changes in cortisol-regulating genes in both the placental and fetal tissue among women in the higher choline intake group. “The study findings raise the exciting possibility that a higher maternal choline intake may counter some of the adverse effects of prenatal stress on behavioral, neuroendocrine, and metabolic development in the offspring,” says Marie Caudill, PhD, Cornell University, who is an author of the study and a leading choline researcher.

Choline: A Vital Nutrient

Choline is especially important for pregnant women – it has been shown to play an important role in fetal and infant brain development, affecting the areas of the brain responsible for memory and life-long learning ability. In addition, research shows women with diets low in choline have four times greater risk of having babies with neural tube defects, such as spina bifida (4).

Emerging research also shows choline may have additional benefits in other areas, including:

  • Breast cancer prevention: A study funded by the National Institutes of Health concluded that dietary choline is associated with a 24 percent reduced risk of breast cancer (5).
  • Anti-inflammatory: Foods rich in choline may help reduce the risk of inflammation associated with chronic diseases such as cardiovascular disease, bone loss, dementia and Alzheimer’s disease (6).
  • Brain function: Choline also promotes adult brain function by preserving the structure of brain cell membranes and is an essential component of acetylcholine, the neurotransmitter involved in memory function and muscle control (7).

The Incredible Excellent Source of Choline

Despite its important role in the body, only one in 10 Americans is meeting the Adequate Intake (AI) guidelines for choline (8). Eggs are an excellent source of choline, containing 125 mg per egg. Neva Cochran, registered dietitian and nutrition communications consultant, explains that the nutritional benefits of eggs are not merely limited to choline. “Not only are eggs an excellent source of choline, they contain many other nutrients pregnant women need most, such as high-quality protein, iron and folate—all for just about 15 cents apiece,” says Cochran.

In order to get adequate amounts of choline, Cochran suggests the following tips:

  • Find it in Food: A great way to get your daily dose of choline is to include choline-rich foods in the diet, such as eggs, lean beef, cauliflower and peanuts. Also keep in mind most multivitamins, even prenatal vitamins, provide far less than the Adequate Intake for choline.
  • Don’t Skip the Yolk: Choline is found exclusively in the egg yolk, not the white. Nearly half of the protein and most of the vitamins and minerals are also contained in the yolk.

 

References

1. Jiang, X., J. Yan, A. A. West, C. A. Perry, O. V. Malysheva, S. Devapatla, E. Pressman, F. Vermeylen, and M. A. Caudill. Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans. FASEB J 2012; 26: 3563-3574.

2. Levitt, N. S., Lindsay, R. S., Holmes, M. C., and Seckl, J. R. Dexamethasone in the last week of pregnancy attenuates hippocampal glucocorticoid receptor gene expression and elevates blood pressure in the adult offspring in the rat. Neuroendocrinology 1996; 64: 412.

3. Levitt, N. S., Lambert, E. V., Woods, D., Hales, C. N., Andrew, R., and Seckl, J. R. Impaired glucose tolerance and elevated blood pressure in low birth weight, nonobese, young South African adults: early programming of cortisol axis. J Clin Endocrinol Metab 2000; 85: 4611.

4. Shaw GM, et al. Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am J Epidemiol 2004; 160: 102-9.

5. Xu X, et al. Choline metabolism and risk of breast cancer in population-based study. FASEB J 2008; 22: 1-8.

6. Cho E, et al. Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. AJCN 2006; 83: 905-11.

6. Cho E, et al. Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. AJCN 2006; 83: 905-11.

7. Moeller SM, et al. The Potential Role of Dietary Xanthophylls in Cataract and Age-Related Macular Degeneration. J Am Coll Nutr 2000; 19 (5): 522S-527S.

8. Jensen HH, et al. Choline in the diets of the US population: NHANES, 2003-2004. Abstract presented at Experimental Biology 2007.

 

Increase in RDA for Vitamin C Could Help Reduce Heart Disease, Stroke, Cancer

The recommended dietary allowance, or RDA, of vitamin C is less than half what it should be, scientists argue in a recent report, because medical experts insist on evaluating this natural, but critical nutrient in the same way they do pharmaceutical drugs and reach faulty conclusions as a result.

The researchers, in Critical Reviews in Food Science and Nutrition, say there’s compelling evidence that the RDA of vitamin C should be raised to 200 milligrams per day for adults, up from its current levels in the United States of 75 milligrams for women and 90 for men.

Rather than just prevent the vitamin C deficiency disease of scurvy, they say, it’s appropriate to seek optimum levels that will saturate cells and tissues, pose no risk, and may have significant effects on public health at almost no expense – about a penny a day if taken as a dietary supplement.

“It’s time to bring some common sense to this issue, look at the totality of the scientific evidence, and go beyond some clinical trials that are inherently flawed,” said Balz Frei, professor and director of the Linus Pauling Institute at Oregon State University, and one of the world’s leading experts on the role of vitamin C in optimum health.

“Significant numbers of people in the U.S. and around the world are deficient in vitamin C, and there’s growing evidence that more of this vitamin could help prevent chronic disease,” Frei said. “The way clinical researchers study micronutrients right now, with the same type of so-called ‘phase three randomized placebo-controlled trials’ used to test pharmaceutical drugs, almost ensures they will find no beneficial effect. We need to get past that.”

Unlike testing the safety or function of a prescription drug, the researchers said, such trials are ill suited to demonstrate the disease prevention capabilities of substances that are already present in the human body and required for normal metabolism. Some benefits of micronutrients in lowering chronic disease risk also show up only after many years or even decades of optimal consumption of vitamin C – a factor often not captured in shorter-term clinical studies.

A wider body of metabolic, pharmacokinetic, laboratory and demographic studies suggests just the opposite, that higher levels of vitamin C could help reduce the chronic diseases that today kill most people in the developed world – heart disease, stroke, cancer, and the underlying issues that lead to them, such as high blood pressure, chronic inflammation, poor immune response and atherosclerosis.

“We believe solid research shows the RDA should be increased,” Frei said. “And the benefit-to-risk ratio is very high. A 200 milligram intake of vitamin C on a daily basis poses absolutely no risk, but there is strong evidence it would provide multiple, substantial health benefits.”

An excellent diet with the recommended five to nine daily servings of fruits and raw or steam-cooked vegetables, together with a six-ounce glass of orange juice, could provide 200 milligrams of vitamin C a day. But most Americans and people around the world do not have an excellent diet.

Even at the current low RDAs, various studies in the U.S. and Canada have found that about a quarter to a third of people are marginally deficient in vitamin C, and up to 20 percent in some populations are severely deficient – including college students, who often have less-than-perfect diets. Smokers and older adults are also at significant risk.

Even marginal deficiency can lead to malaise, fatigue, and lethargy, researchers note. Healthier levels of vitamin C can enhance immune function, reduce inflammatory conditions such as atherosclerosis, and significantly lower blood pressure.

  • A recent analysis of 29 human studies concluded that daily supplements of 500 milligrams of vitamin C significantly reduced blood pressure, both systolic and diastolic. High blood pressure is a major risk factor for heart disease and stroke, and directly attributes to an estimated 400,000 deaths annually in the U.S.
  • A study in Europe of almost 20,000 men and women found that mortality from cardiovascular disease was 60 percent lower when comparing the blood plasma concentration of vitamin C in the highest 20 percent of people to the lowest 20 percent.
  • Another research effort found that men with the lowest serum vitamin C levels had a 62 percent higher risk of cancer-related death after a 12-16 year period, compared to those with the highest vitamin C levels.

Laboratory studies with animals – which may be more accurate than human studies because they can be done in controlled conditions and with animals of identical genetic makeup – can document reasons that could explain all of these findings, Frei said.

Critics have suggested that some of these differences are simply due to better overall diet, not vitamin C levels, but the scientists noted in this report that some health benefits correlate even more strongly to vitamin C plasma levels than fruit and vegetable consumption.

Scientists in France and Denmark collaborated on this report. Research at OSU on these issues has been supported by the National Center for Complementary and Alternative Medicine, a division of the National Institutes of Health.

 

Reference 

Frei B, Birlouez-Aragon I, Lykkesfeldt J. Authors’ Perspective: What is the Optimum Intake of Vitamin C in Humans? Crit Rev Food Sci Nutr 2012; 52 (9): 815-29.

 

Fukushima Radiation Release is Worse than You Have Been Told

What You Can Do to Protect Yourself

by Steve Hickey, PhD; Atsuo Yanagisawa, MD, PhD; Andrew W. Saul, PhD; Gert E. Schuitemaker, PhD; Damien Downing, MD

People have been misinformed about the tragedy at Fukushima and its consequences. There is a continuing cover up, the reactors have not been stabilized, and radiation continues to be released. The Japanese College of Intravenous Therapy (JCIT) has recently released a video for people wishing to learn more about how to protect themselves from contamination by taking large doses of vitamin C.

 

 

Japanese Government Minimizes Danger; Ignores Vitamin C

In the fall of 2011, JCIT presented a study that Fukushima workers had abnormality gene expression, which may be avoided using dietary antioxidants, especially vitamin C. The data was presented in Japan, Taiwan, and Korea. The JCIT sent letters to the government urging the government to tell the people how they may protect themselves from radiation. To date, the recommendation has been ignored by Japanese government and TEPCO (Tokyo Electric Power Company).

Linus Pauling gained the Nobel Peace Prize in part based on his calculations of the number of deaths from nuclear weapons fallout (1). He was supported by physicist and father of the Soviet bomb Andrei Sakharov, who also later received the Nobel Prize for peace (2). These and other scientists estimated that there would be an extra 10,000 deaths worldwide for each megaton nuclear test in the atmosphere. A nuclear reactor can contain much more radioactive material than a nuclear weapon. Fukushima had six reactors, plus stored additional radioactive material and nuclear waste.

How Radiation Damages Cells

Ionizing radiation acts to damage living tissue by forming free radicals. Essentially, electrons are ripped from molecules. Removing an electron from an atom or molecule turns it into an ion, hence the term ionizing radiation. X-rays, gamma rays, alpha- and beta-radiation are all ionizing.

Most of the damage occurs from ionizing radiation generating free radicals in water, as water molecules are by far the most abundant in the body. While avoiding unnecessary exposure to ionizing radiation is clearly preferable, people affected by Fukushima do not have the luxury of avoiding contamination.

Antioxidants: Free-Radical Scavengers

Free-radical scavengers, as the name suggests, mop up the damaging radicals produced by radiation. The more common term for free radical scavenger is antioxidant. Antioxidants replace the electrons stripped from molecules by ionizing radiation. Antioxidants have long been used in the treatment of radiation poisoning (3-7). Most of the harm from ionizing radiation occurs from free radical damage which may be quenched by the free electrons antioxidants provide. Fortunately, safe antioxidants are widely available as nutritional supplements. Vitamin C is the prime example.

Why Vitamin C?

Vitamin C is of particular importance and should be included at high intakes for anyone trying to minimize radiation poisoning. High dose vitamin C provides continual antioxidant flow through the body. It is absorbed from the gut and helps to replenish the other antioxidants. When it is used up, it is excreted in the urine. Importantly, it can chelate, or grab onto, radioactive heavy metal atoms and help eliminate them from the body. Large dynamic flow doses of vitamin C (about 3,000 mg, taken 4 times a day for a total of 12,000 mg) would exemplify antioxidant treatment. Higher doses have been used by Dr. Atsuo Yanagisawa and colleagues (8-9).

Shortly after the disaster, Dr. Damien Downing described how supplements can help protect against radioactive fallout (10). OMNS issued an update on the response to Fukushima in Japan (11). Recently, Dr. Gert Schuitemaker has provided a review of vitamin C as a radio-protectant for Fukushima contamination (12).

Persons living in the areas affected by radioactive contamination can take antioxidant supplements, especially high doses of vitamin C, to counteract the negative consequences of long-term low dose radiation exposure, as well as to protect the health of coming generations.(12, 13). People who have a possible internal or external radiation exposure should take antioxidant supplements to maintain an optimal antioxidant reserve. Because of the enormous size and oceanic spread of Fukushima contamination, this literally applies to everyone.

(Orthomolecular Medicine News ServiceMay 14, 2012)

 

“The International Society for Orthomolecular Medicine is pleased to have participated in the making of this important DVD on the protective effects of intravenous vitamin C on radiation exposure from the Fukushima nuclear plant in March 2011. We are in full support of the valuable work of Dr. Yanagisawa and his colleagues, and we very much appreciate the commitment of Mr. Daisuke Shibata, who has made it possible for the free distribution of the video around the world. May this orthomolecular message raise awareness and foster improvement in the treatment of radiation exposure.”

Steven Carter
Director, International Society for Orthomolecular Medicine

 

References

1. The Nobel Foundation (1962) The Nobel Peace Prize 1962, Linus Pauling Biography.

2. Sakharov A. (1975) The Nobel Peace Prize 1975, Andrei Sakharov, Autobiography.

3. Brown SL, Kolozsvary A, Liu J, et al: Antioxidant diet supplementation starting 24 hours after exposure reduces radiation lethality. Radiat Res 2010; 173: 462-8.

4. Zueva NA, Metelitsa LA, Kovalenko AN, et al: Immunomodulating effect of berlithione in clean-up workers of the Chernobyl nuclear plant accident [Article in Russian]. Lik Sprava 2002; (1): 24-26.

5. Yamamoto T, Kinoshita M et al. Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation. J Radiat Res (Tokyo) 2010; 51 (2): 145-56.

6. Gaby A. Intravenous Nutrient Therapy: the “Myers’ Cocktail”. Alt Med Rev 2002; 7 (5): 389:403.

7. Narra VR, Howell RW, Sastry KS, Rao DV. Vitamin C as a radioprotector against iodine-131 in vivo. J Nucl Med 1993; 34 (4): 637-40.

8. Yanagisawa A. Orthomolecular approaches against radiation exposure. Presentation Orthomolecular Medicine Today Conference. Toronto 2011.

9. Green MH, Lowe JE et al. Effect of diet and vitamin C on DNA strand breakage in freshly-isolated human white blood cells. Mutat Res 1994; 316(2):91-102

10. Downing D. (2011) Radioactive Fallout: Can Nutritional Supplements Help? A Personal Viewpoint. Orthomolecular Medicine News Service, May 10.

11. OMNS (2012) Vitamin C Prevents Radiation Damage, Nutritional Medicine in Japan. Orthomolecular Medicine News Service, February 1.

12. Schuitemaker GE. Vitamin C as protection against radiation exposure. J Orthomolecular Med 2011, 26: 3; 141-145. [Also in Dutch: Schuitemaker G.E. Radioactiviteit in Japan: Orthomoleculair antwoord. Ortho 2011:3, June.

13. Yanagisawa A, Uwabu M, Burkson BE, Weeks BS, Hunninghake R, Hickey S, Levy T, (2011) Environmental radioactivity and health. Official JCIT Statement, March 29.

 

Prenatal Choline May Program Healthier Babies

Increased maternal intake of the nutrient choline could reduce their kid’s chances of developing hypertension and diabetes later in life.

In a study led by Marie Caudill, associate professor of nutritional sciences, and graduate student Xinyin Jiang, a group of third-trimester pregnant women consumed 930 milligrams of choline, more than double the recommended 450 milligram daily intake.

The result for their babies was 33 per cent lower concentrations of cortisol – a hormone produced in response to stress that also increases blood sugar – compared to those from a control group of women who consumed about 480 milligrams of choline.

Caudill believes this happened because the choline changed the expression patterns of genes involved in cortisol production.

The work is the first human study to suggest a role for choline in the “programming” of key biological processes in the baby.

“The study findings raise the exciting possibility that a higher maternal choline intake may counter some of the adverse effects of prenatal stress on behavioral, neuroendocrine and metabolic development in the offspring,” Caudill said.

This could be especially useful for women experiencing anxiety and depression during their pregnancy, as well as conditions such as pre-eclampsia.

“A dampening of the baby’s response to stress as a result of mother consuming extra choline during pregnancy would be expected to reduce the risk of stress-related diseases such as hypertension and type 2 diabetes throughout the life of the child,” she said.

She said additional studies are needed to confirm the study findings and further explore long-term effects. Dietary sources of choline include egg yolks, beef, pork, chicken, milk, legumes and some vegetables. Most prenatal vitamin supplements do not include choline.

“We hope that our data will inform the development of choline intake recommendations for pregnant women that ensure optimal fetal development and reduce the risk of stress-related diseases,” Caudill added.

The study has been published online in The Journal of the Federation of American Societies for Experimental Biology.

 

Reference

Jiang X, Yan J, West AA, Perry CA, Malysheva OV, Devapatla S, Pressman E, Vermeylen F, Caudill MA. Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans. FASEB J. 2012 May 1. [Epub ahead of print]

 

Researchers Find Potential ‘Dark Side’ to Diets High in Beta-Carotene

New research suggests that there could be health hazards associated with consuming excessive amounts of beta-carotene.

This antioxidant is a naturally occurring pigment that gives color to foods such as carrots, sweet potatoes and certain greens. It also converts to vitamin A, and foods and supplements are the only sources for this essential nutrient.

But scientists at Ohio State University have found that certain molecules that derive from beta-carotene have an opposite effect in the body: They actually block some actions of vitamin A, which is critical to human vision, bone and skin health, metabolism and immune function.

Because these molecules derive from beta-carotene, researchers predict that a large amount of this antioxidant is accompanied by a larger amount of these anti-vitamin-A molecules, as well.

Professor Earl Harrison

Vitamin A provides its health benefits by activating hundreds of genes. This means that if compounds contained in a typical source of the vitamin are actually lowering its activity instead of promoting its benefits, too much beta-carotene could paradoxically result in too little vitamin A.

The findings also might explain why, in a decades-old clinical trial, more people who were heavily supplemented with beta-carotene ended up with lung cancer than did research participants who took no beta-carotene at all. The trial was ended early because of that unexpected outcome.

The scientists aren’t recommending against eating foods high in beta-carotene, and they are continuing their studies to determine what environmental and biological conditions are most likely to lead to these molecules’ production.

“We determined that these compounds are in foods, they’re present under normal circumstances, and they’re pretty routinely found in blood in humans, and therefore they may represent a dark side of beta-carotene,” said Earl Harrison, Dean’s Distinguished Professor ofHuman Nutrition at Ohio State and lead author of the study. “These materials definitely have anti-vitamin-A properties, and they could basically disrupt or at least affect the whole body metabolism and action of vitamin A. But we have to study them further to know for sure.”

The study is scheduled for publication in the May 4, 2012, issue of theJournal of Biological Chemistry.

Previous research has already established that when beta-carotene is metabolized, it is broken in half by an enzyme, which produces two vitamin A molecules.

In this new study, the Ohio State researchers showed that some of these molecules are produced when beta-carotene is broken in a different place by processes that are not yet fully understood and act to antagonize vitamin A.

Harrison is an expert in the study of antioxidants called carotenoids, which give certain fruits and vegetables their distinctive colors. Carotenoids’ antioxidant properties are associated with protecting cells and regulating cell growth and death, all of which play a role in multiple disease processes.

For this work, he joined forces with co-authors Robert Curley, professor of medicinal chemistry and pharmacognosy, and Steven Schwartz, professor of food science and technology, both at Ohio State. Curley specializes in producing synthetic molecules in the pursuit of drug development, and Schwartz is an expert at carotenoid analysis.

Curley manufactured a series of beta-carotene-derived molecules in the lab that match those that exist in nature. The researchers then exposed these molecules to conditions mimicking their metabolism and action in the body.

Of the 11 synthetic molecules produced, five appeared to function as inhibitors of vitamin A action based on how they interacted with receptors that would normally launch the function of vitamin A molecules.

“The original idea was that maybe these compounds work the way vitamin A works, by activating what are called retinoic acid receptors. What we found was they don’t activate those receptors. Instead, they inhibit activation of the receptor by retinoic acid,” Curley said. “From a drug point of view, vitamin A would be called an agonist that activates a particular pathway, and these are antagonists. They compete for the site where the agonist binds, but they don’t activate the site. They inhibit the activation that would normally be expected to occur.”

Once that role was defined, the researchers sought to determine how prevalent these molecular components might be in the human body. Analyzing blood samples obtained from six healthy human volunteers, the scientists in the Schwartz lab found that some of these anti-vitamin-A molecules were present in every sample studied, suggesting that they are a common product of beta-carotene metabolism.

The compounds also have been found previously in cantaloupe and other orange-fleshed melons, suggesting humans might even absorb these molecules directly from their diet.

Harrison noted that the findings might explain the outcome of a well-known clinical trial that has left scientists puzzled for years. In that trial, people at high risk for lung cancer – smokers and asbestos workers – were given massive doses of beta-carotene over a long period of time in an attempt to lower that risk. The trial ended early because more supplemented participants developed cancer than did those who received no beta-carotene. This outcome was reinforced by results of a follow-up animal study.

“Those trials are still sending shockwaves 20 years later to the scientific community,” said Harrison, also an investigator in Ohio State’s Comprehensive Cancer Center. “What we found provides a plausible explanation of why larger amounts of beta-carotene might have led to unexpected effects in these trials.”

The research also has implications for efforts to bio-engineer staple crops in developing countries so they contain excess beta-carotene, which is considered a sustainable way to provide these populations with pro-vitamin A. Existing projects include production of golden rice in Asia, golden maize in South America and cassava in Africa.

“A concern is that if you engineer these crops to have unusually high levels of beta-carotene, they might also have high levels of these compounds,” Harrison said.

The researchers are continuing to study these compounds, including whether food processing or specific biological processes affect their prevalence. Previous studies have suggested that oxidative stress, which can result from smoking and air pollution exposure, can lead to higher production of these anti-vitamin-A molecules, Harrison noted.

This research was supported by the National Institutes of Health and the Ohio Agricultural Research and Development Center.

Additional co-authors include Abdulkerim Eroglu, Carlo dela Sena and Sureshbabu Narayanasamy of the Department of Human Nutrition; Damian Hruszkewycz of the College of Pharmacy; and Ken Riedl and Rachel Kopec of the Department of Food Science and Technology, all at Ohio State. Harrison, Curley, Eroglu and dela Sena also are affiliated with Ohio State’s Biochemistry Program.

 

Vitamin E in Diet Protects Against Many Cancers

Researchers find form commonly used in supplements has no such benefit. 

Vitamin E in vegetable oils and nuts prevents cancer, according to research done at Rutgers University and the Cancer Institute of New Jersey.

Next time you need to choose between vegetable oil and margarine in that favorite recipe, think about your health and reach for the oil.

While the question of whether vitamin E prevents or promotes cancer has been widely debated in scientific journals and in the news media, scientists at the Center for Cancer Prevention Research, at Rutgers Mario School of Pharmacy, and the Cancer Institute of New Jersey, believe that two forms of vitamin E – gamma and delta-tocopherols – found in soybean, canola and corn oils as well as nuts do prevent colon, lung, breast and prostate cancers.

“There are studies suggesting that vitamin E actually increases the risk of cancer and decreases bone density,” says Chung S. Yang, director of the center. “Our message is that the vitamin E form of gamma-tocopherols, the most abundant form of vitamin E in the American diet, and delta-tocopherols, also found in vegetable oils, are beneficial in preventing cancers while the form of vitamin E, alpha- tocopherol, the most commonly used in vitamin E supplements, has no such benefit.”

Director of the Center for Cancer Prevention Research at Rutgers Ernest Mario School of Pharmacy

Yang and colleagues, Nanjoo Suh and Ah-Ng Tony Kong, summarized their findings recently in Cancer Prevention Research, a journal of the American Association for Cancer Research. In a Commentary, Does Vitamin E Prevent or Promote Cancer? the Rutgers scientists discuss animal studies done at Rutgers as well as human epidemiological studies that have examined the connection between vitamin E and cancer.

Yang says Rutgers scientists conducting animal studies for colon, lung, breast and prostate cancer found that the forms of vitamin E in vegetable oils, gamma and delta-tocopherols, prevent cancer formation and growth in animal models.

“When animals are exposed to cancer-causing substances, the group that was fed these tocopherols in their diet had fewer and smaller tumors,” Yang says. “When cancer cells were injected into mice these tocopherols also slowed down the development of tumors.”

In researching colon cancer, Yang pointed to another recently published paper in Cancer Prevention Research indicating that the delta-tocopherol form of vitamin E was more effective than other forms of vitamin E in suppressing the development of colon cancer in rats.

This is good news for cancer research. Recently, in one of the largest prostate cancer clinical trials in the United States and Canada, scientists found that the most commonly used form of vitamin E supplements, alpha-tocopherol, not only did not prevent prostate cancer, but its use significantly increased the risk of this disease among healthy men.

This is why, Yang says, it is important to distinguish between the different forms of vitamin E and conduct more research on its cancer preventive and other biological effects.

“For people who think that they need to take vitamin E supplements,” Yang says, “taking a mixture of vitamin E that resembles what is in our diet would be the most prudent supplement to take.”

 

Reference

Yang CS, Suh N, Kong AN. Does Vitamin E Prevent or Promote Cancer? Cancer Prev Res (Phila). 2012 Apr 16. [Epub ahead of print]

 

Big doses of vitamin C may lower blood pressure

Taking large doses of vitamin C may moderately reduce blood pressure, according to an analysis of years of research by Johns Hopkins scientists. But the researchers stopped short of suggesting people load up on supplements.

“Our research suggests a modest blood pressure lowering effect with vitamin C supplementation, but before we can recommend supplements as a treatment for high blood pressure, we really need more research to understand the implications of taking them,” says Edgar “Pete” R. Miller III, M.D., Ph.D., an associate professor in the division of general internal medicine at the Johns Hopkins University School of Medicine and leader of the study published in the American Journal of Clinical Nutrition.

Roughly 30 percent of adults in the United States have high blood pressure, or hypertension, an important risk factor for heart disease and stroke. Successful treatment may include drugs, exercise, weight loss, and dietary changes such as reducing salt intake. Some experts believe that large amounts of vitamin C, an essential micronutrient found primarily in fruits and vegetables, could lower pressure as well, but randomized, controlled dietary intervention studies — the gold standard of nutrition research — have produced mixed results.

Miller and his colleagues reviewed and analyzed data from 29 randomized, controlled, previously published clinical trials that reported systolic and/or diastolic blood pressure values and also compared vitamin C intake to a placebo. What they found is that taking an average of 500 milligrams of vitamin C daily — about five times the recommended daily requirement — reduced blood pressure by 3.84 millimeters of mercury in the short term. Among those diagnosed with hypertension, the drop was nearly 5 millimeters of mercury.

By comparison, Miller says, patients who take blood pressure medication such as ACE inhibitors or diuretics (so-called “water pills”) can expect a roughly 10 millimeter of mercury reduction in blood pressure.

Five hundred milligrams of vitamin C is the amount in about six cups of orange juice. The recommended daily intake of vitamin C for adults is 90 milligrams.

“Although our review found only a moderate impact on blood pressure, if the entire U.S. population lowered blood pressure by 3 milliliters of mercury, there would be a lot fewer strokes,” Miller says. Miller cautions, however, that none of the studies his team reviewed show that vitamin C directly prevents or reduces rates of cardiovascular disease, including stroke.

Scientists have focused on vitamin C’s potential role in blood pressure reduction because of the nutrient’s biological and physiological effects. For example, vitamin C may act as a diuretic, causing the kidneys to remove more sodium and water from the body, which helps to relax the blood vessel walls, thereby lowering blood pressure.

Nutritional supplements are a USD 28 billion-a-year industry, and marketing claims, newspaper stories and testimonials often make them hard to resist, Miller says. People often view supplements as a “natural alternative” and preferable to drugs for high blood pressure or other ailments, he adds, despite mounting evidence that many supplements don’t work and in some cases may cause harm.

“People love to take vitamins regardless of the evidence or lack of it,” Miller says. “We’re trying to raise the bar and provide evidence-based guidance about whether supplements help or actually do harm.” With respect to vitamin C, he says, the jury is still out.

Other study authors from Johns Hopkins include Stephen P. Juraschek, an M.D., Ph.D. candidate; Eliseo Guallar, M.D., Dr.Ph.; and Lawrence J. Appel, M.D., M.P.H.

 

Reference 

Juraschek SP, Guallar E, Appel LJ, Miller ER 3rd. Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2012 Apr 4. [Epub ahead of print]

 

Intravenous Vitamin C May be Beneficial in Treatment of Shingles

Intravenously administered ascorbic acid may have beneficial effects on herpes zoster-associated pain, lesions and accompanying complaintsThis according to a German study published in the April 2012 issue of the Medical Science Monitor. 

Not only the acute symptoms of herpes zoster can be diminished by high-dose vitamin C. Even long-term sequelae, like painful postherpetic neuralgia, may be mitigated or even fully avoided. 

 

Martin Schencking, Claudia Vollbracht, Gabriele Weiss, Jennifer Lebert, Andreas Biller, Birgitt Goyvaerts, and Karin Kraft

Intravenous Vitamin C in the treatment of shingles: Results of a multicenter prospective cohort study
Med Sci Monit 2012; 18 (4): CR 215-224 

 

ABSTRACT

Background: Vitamin C is an immune-relevant micronutrient, which is depleted in viral infections and this deficiency seems to play a critical role in the pathogenesis of herpes infections and in the development of postherpetic neuralgia. The objective of this observational multicenter study was to evaluate the utilization, safety and efficacy of intravenously administrated vitamin C in patients with shingles.

Material/Methods: Between April 2009 and December 2010 16 general practitioners recorded data of 67 participants with symptomatic herpes zoster who received vitamin C intravenously (Pascorbin® 7.5 g/50 ml) for approximately 2 weeks in addition to standard treatment. The assessment of pain (VAS) and the dermatologic symptoms of shingles such as hemorrhagic lesions and the number of efflorescences were investigated in a follow-up observation phase of up to 12 weeks.

Results: Mean declines of pain scores (VAS), number of affected dermatomes and efflorescences, and the presence of hemorrhagic vesicles between the baseline and follow-up assessments at 2 and 12 weeks were statistically significant. Overall, 6.4% of the participants experienced post-herpetic neuralgia. Common complaints such as general fatigue and impaired concentration also improved during the study. The effects and the tolerability of the treatment were evaluated positively by the physicians. The risk of developing PHN was reduced.

Conclusions: The data presented here provide evidence that concomitant use of intravenously administered ascorbic acid may have beneficial effects on herpes zoster-associated pain, dermatologic findings and accompanying common complaints. To confirm our findings, randomized, placebo-controlled clinical studies are necessary.