In a recent clinical review on autism and vitamin D, Dr. Eva Kocovska and colleagues from the University of Glasgow called for “urgent research” on vitamin D’s role in autism.

Kočovská E, Fernell E, Billstedt E, Minnis H, Gillberg C. Vitamin D and autism: Clinical review. Res Dev Disabil. 2012 Apr 20;33(5):1541-1550. [Epub ahead of print]

The body of the paper consisted of a review of the 35 papers published to date that deal directly with autism and vitamin D. Here were their areas of interest and the studies they reviewed.

On vitamin D blood levels

Four studies have looked at vitamin D levels in autistic children or their mothers and all have found low levels (<30 ng/ml) in autistic children. One found no difference in vitamin D levels between autistic children and boys with acute inflammation (a curious control), while the other three found differences, some significant and some not. One study found Somali mothers with autistic children had average vitamin D levels of 6.7 ng/ml, about 30% lower than Somali mothers without autistic children.

On vitamin D intake

The authors examined about a dozen papers that looked at vitamin D intake in autistic children, all finding that most autistic children do not meet vitamin D intake requirements for their age. On a side note, the authors also mention that magnesium has a crucial role in brain development and function. As readers know, magnesium deficiencies are the rule, not the exception in most Americans.

On brain development and function

The authors reviewed the numerous ways vitamin D is involved in brain development and function, including:

•  Synaptic development
•  Nerve migration and growth
•  Neurotransmission, both excitatory and inhibitory
•  Preventing excessive cell proliferation
•  Orchestrating signaling pathways in the brain
•  Cell differentiation
•  Nerve growth factor expression
•  Regulation of inflammatory cytokines
•  Neurotransmitter synthesis
•  Intra-neuronal calcium signaling
•  Anti-oxidant activity
•  Control of the expression of genes involved in brain structure and metabolism
•  Regulation of glutathione, the master antioxidant and heavy metal remover
•  Protection from glutamate toxicity

On autism, vitamin D and seizures

I was surprised at the number of studies showing the connection between vitamin D, seizures and autism. Up to 30% of children with autism have seizures, and it may be as easy as giving a vitamin D supplement to reduce seizures.

On breastfeeding

A recent study showed in a statistically significant finding that in States where exclusive breastfeeding is the highest, autism incidence is also the highest. Remember, unless the mother takes 5,000 IU/day and has a vitamin D level > 40 ng/ml, breast milk contains little vitamin D.

Yes, as I have been saying since 2006, there is a need for “urgent research in the field.”

More than 60 years ago, based on the science of the time (science that has stagnated for 60 years), Dr. E. Orbermer of Italy wrote the following:

“Until further experimental evidence, adequate and incontrovertible, is made available, I submit that we should play for safety. In a climate like that of England every pregnant woman should be given a supplement of vitamin D in doses of not less than 10,000 IU per day in the first 7 months, and 20,000 IU (per day) during the 8th and 9th months.”

OBERMER E. Vitamin-D requirements in pregnancy. Br Med J. 1947 Dec 6;2(4535):927.

The “adequate and incontrovertible evidence” that Dr. Orbermer wanted, to a certain extent, is finally here, 60 years later. As it has to do with developing human beings, it could not be more important. The study is the highest standard of proof, a randomized controlled trial, conducted by Professor Bruce Hollis and colleagues at the Medical University of South Carolina. They took 350 pregnant women, gave 1/3 of them 600 IU/day, 1/3 of them 2,000 IU/day, and 1/3 4,000 IU/day. Then they waited to see, among many things, which group would produce infants with at least 20 ng/ml of vitamin D in their blood, the lowest limit the 2010 Food and Nutrition Board (FNB) says is needed for good fetal health.

Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 2011 Oct;26(10):2341-57. doi: 10.1002/jbmr.463

Surprise surprise, only the 4,000 IU/day pregnant women group even approached the minimal safety level of 20 ng/ml in their infants. Furthermore, the 2010 FNB recommendations of vitamin D in prenatal vitamins would have left 50% of the White women and 80% of the Black women with fetuses below 20 ng/ml.

However, Professor Hollis found something else, something potentially much more important. He found that the average fetus in the USA is starved for enough building blocks for his or her mother to make adequate activated vitamin D to ship to the baby; activated vitamin D that is probably used for microscopic organ development, such as in the brain.

Activated vitamin D in pregnancy is mysterious. It appears the mother makes it in her kidney (maybe some in her placenta) at levels up to 3 to 4 times normal (without maternal hypercalcemia) and ships it across to the fetus. This only happens if the mother has enough of this vital steroid hormone in her body to ship to the fetus and most mothers do not. If she can’t make it, she can’t ship it maximally, and the 38 fetal organs depending on activated vitamin D to fully develop must do the best they can do with inadequate amounts of this steroid. Of course, none of this applies to mothers who frequently sunbathe, or who take 5,000 IU/day while they are pregnant.

To quote Professor Hollis: “These findings suggest that the current vitamin D (requirements for pregnancy, currently 600 IU/day) issued in 2010 by the Food and Nutrition Board should be raised to 4,000 IU of vitamin D per day so that all women, regardless of race, can attain optimal nutritional and hormonal vitamin D status throughout pregnancy.”

The Vitamin D Council agrees and considers this an important study in support of why adults and pregnant women need at least 4,000 IU/day to elevate blood levels and improve fetal health and birth outcomes. Although there are no trials that support taking more, the Vitamin D Council believes 5,000 IU/day is equally safe and would be more effective at maintaining adequate fetal blood levels of vitamin D.

In a paper critical of higher levels of vitamin D for allegedly increasing a marker of inflammation, c-reactive protein (CRP), Drs. Muhammad Amer and Rehan Qayyum of the Johns Hopkins School of Medicine, began their paper by saying:

“The cardiovascular protection offered by vitamin D and its analogues is probably mediated by modulation of inflammatory cytokines.”

Amer M, Qayyum R. Relation Between Serum 25-Hydroxyvitamin D and C-Reactive Protein in Asymptomatic Adults (From the Continuous National Health and Nutrition Examination Survey 2001 to 2006). Am J Cardiol. 2011 Oct 12.

If you will notice, both physicians know that vitamin D offers “cardiovascular protection.” However, they are concerned 25(OH)D levels higher than 20 ng/ml will increase inflammation as measured by CRP and thus worsen cardiovascular protection. CRP is a protein in the blood which tends to rise in response to inflammation or injury. Its physiologic role is to take part in the “complement system.”

The authors arrived at this conclusion by adjusting their data for up to 9 variables and finding that a 25(OH)D of 20 ng/ml is associated with a CRP (range 0-5) of approximately 1.7 while a 25(OH)D of 50 ng/ml is associated with a CRP of 1.9. Their raw findings contradict their adjusted data in that the raw data showed what we have known for some time and that is that in the lower ranges of 25(OH)D, vitamin D reduces CRP. As with most biomarkers of vitamin D, the big improvement is in people who get their 25(OH)D up  from 5 ng/ml up to 20 ng/ml. We know that in most cases, the biggest bang for the buck is in treating severe deficiency in people with such low levels.

So if you have natural levels of vitamin D, say a 25(OH)D of 50 ng/ml, and you want to decrease your CRP by 0.2, then stop your vitamin D and stay out of the sun, get your levels to 20 ng/ml, and see if all the corrections and adjustments the doctors performed were correct. I certainly am not going to do such a silly thing.

Dozens of studies now exist showing supplemental vitamin D3 reduces mortality rates, in part due to its cardiovascular protection. The majority of these studies show that improvement in mortality continues through 30 ng/ml and even up to 40 ng/ml. Not enough people have levels of 50 ng/ml for scientists to see if such levels offer further protection. However, cardiovascular disease is rare in native peoples around the equator where vitamin D levels of 50 ng/ml are not uncommon.

The takeaway message from this paper is that scientists will need to recalculate lots of different “normals,” using vitamin D sufficient subjects. It’s not just that normal CRP may be a bit higher in vitamin D sufficient people, their red blood count and the protein albumin may be a bit lower, for example. The point is that pathologists and epidemiologists will need to redo much of their work. We don’t know the normal range of CRP in 65-year-old men; we know the range of CRP in 65-year-old vitamin D deficient men. Likewise, we don’t know the incidence of heart disease in 65-year-old men; we know the incidence of heart disease in vitamin D deficient 65 year-old men. We have lots of work to do.

Source: Vitamin D Council Newsletter

http://www.foodmanufacture.co.uk/Ingredients/Criminals-drop-drugs-for-food-fraud

When we talk about T scores, osteopenia and osteoporosis, we assume we are talking about older people, especially post-menopausal women. However, a group of obstetricians and pediatricians from the University of Sienna, led by Dr. Franco Bagnoli, reported that 42% of infants have osteopenia.

Bagnoli F, Casucci M, Rossetti A, Nappini S, Cecchi S, Toti S, Franci MB. Vitamin D as a drug. J Matern Fetal Neonatal Med. 2011 Oct;24 Suppl 1:7-11

What I like was that the authors said, “To be safe, vitamin D administration should be increased to 2,000 IU/day for neonates, 5,000 IU/day for children and 10,000 IU/day for all adults.” Obstetricians are generally regarded as the one group of physicians that seldom change their mind. My hat is off to these seven obstetricians.

So many infants have craniotabes, or softening of the fontanels, it is considered normal although such infants show signs of vitamin D deficiency. That is, about a third of our infants show evidence of having low vitamin D during their development in the womb.

Yorifuji J, Yorifuji T, Tachibana K, Nagai S, Kawai M, Momoi T, Nagasaka H, Hatayama H, Nakahata T. Craniotabes in normal newborns: the earliest sign of subclinical vitamin D deficiency. J Clin Endocrinol Metab. 2008 May;93(5):1784-8.

Finally, if you look at the incidence of rickets inside the womb by ultrasound, about a third of infants have signs of intrauterine rickets (splaying or widening of the femur) during their pregnancy.

Mahon P, Harvey N, Crozier S, Inskip H, Robinson S, Arden N, Swaminathan R, Cooper C, Godfrey K; SWS Study Group. Low maternal vitamin D status and fetal bone development: cohort study.J Bone Miner Res. 2010 Jan;25(1):14-9.

Then there is the evidence that vitamin D deficiency during pregnancy is associated infection, toxemia and caesarean section, not to mention a host of diseases as the child ages, including diabetes, asthma, and infections. If you know any pregnant or breastfeeding woman, make sure she is taking at least 6,000 IU/day (10,000 IU/day is fine) and then make sure the child takes 2,000 IU/day of vitamin D when he is weaned and progressively more as he ages, until he is on 5,000 IU/day as a teenager.

However, you and I both know many people will not take supplements or give them to their children, which is why Professor Walter Willett of Harvard believes this is a public health problem that will only be solved through adequate food fortification. Also, prenatal vitamin makers could easily increase the vitamin D in their products up to 4,000 IU/day and stay within the safety guidelines of the Food and Nutrition Board. Many more foods need to be fortified, and these foods need to be foods that all subgroups of people eat in similar amounts, such as cheese and cereals. These foods need to have 400 IU per serving, not 100 IU per serving. I wish I could tell you that I think I will live to see it.

Dr John Cannell