by Ian Wishart
[39] “Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study,” McGrath et al, Schizophrenia Research, Volume 67, Issues 2–3, 1 April 2004, Pages 237–245
[40] “Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness,” Hollis et al, Journal of Bone & Mineral Research, 2011 Oct;26(10):2341-57. doi: 10.1002/jbmr.463
[41] “Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface,” Novakovic et al J. Biol. Chem. 2009, 284, 14838-14848
[42] “Association between Vitamin D Deficiency and Primary Cesarean Section,” Merewood et al, The Journal of Clinical Endocrinology & Metabolism March 1, 2009 vol. 94 no. 3 940-945
[43] “Maternal vitamin D and fetal growth in early-onset severe preeclampsia,” Robinson et al, presented at the 73rd Annual Meeting of the South Atlantic Association of Obstetricians and Gynecologists, Hot Springs, VA, Jan. 30-Feb. 2, 2011.
[44] “The In Utero Effects of Maternal Vitamin D Deficiency – How it Results in Asthma and Other Chronic Diseases,” Weiss and Litonjua, American Journal Of Respiratory And Critical Care Medicine Vol 183 2011:1286-1287
[45] “Fetal origins of adult disease: strength of effects and biological basis,” Barker et al. Int J Epidemiol 2002;
31:1235–1239.
[46] “Being born in winter can mess with your head,” Charles Choi, LivesScience.com, 11 May 2012
[47] “Seasonal Distribution of Psychiatric Births in England,” Disanto et al, PLoS ONE, 7(4): e34866. doi:10.1371/journal.pone.0034866
[48] “Birth seasonality in bipolar disorder, schizophrenia, schizoaffective disorder and stillbirths,” Torrey et al, (1996). Schizophr Res 21: 141–149
[49] “Effect of month of birth on the risk of suicide,” Salib E, Cortina-Borja M (2006). Br J Psychiatry 188: 416–422
[50] “Milk won’t make kids Einsteins,” Daily RX News, May 2012, www.dailyrx.com/news-article/vitamin-d-does-not-improve-academic-performance-or-brains-children-18580.html
CHAPTER 10
MENTAL ILLNESS
“Vitamin D deficiency and insufficiency are both highly prevalent in adolescents with severe mental illness”
– BMC Journal of Psychiatry, 2012
We’ve seen in the previous chapter how a lack of vitamin D during pregnancy can increase the risk of a child developing mental illness. The good news is that in some cases vitamin D can help bring mental illness under control.
The Endocrine Society conference in the US has heard how a group of three women previously diagnosed with major depressive disorder had their lives turned around by the sunshine vitamin. All were on anti-depressants, and had underlying medical conditions including Type 2 diabetes or an underactive thyroid.
Blood tests showed their vitamin D levels had dropped to between 8.9 ng/ml and 14.5 ng/ml – well into deficient and seriously deficient territory. After two to three months of vitamin D supplementation their serum 25(OH)D levels were restored to a healthy 32 to 38 ng/ml.
Using the Beck Depression Inventory, a 21-point survey that rates levels of depression and sadness, one patient moved from clinical severe depression (32 points at baseline) to mild depression (12 points) on completion. Another fell from 26 points (moderate depression) to 8 points (clinically minimal depression), while the third patient moved from moderate to mild.
Sonal Pathak, the US endocrinologist presenting the study, says the implications are fascinating and important:
“Vitamin D may have an as-yet-unproven effect on mood, and its deficiency may exacerbate depression…Screening at-risk depressed patients for vitamin D deficiency and treating it appropriately may be an easy and cost-effective adjunct to mainstream therapies for depression,” he said.[1]
The impact of vitamin D deficiency is widespread. A New Zealand study has found the disorder is common in psychiatric inpatients, schizophrenics and in particular darker-skinned Maori patients.
The research, led by David Menkes at the Waikato Clinical School, reveals 91% of the 102 inpatients studied had sub-optimal (below 30 ng/ml) or deficient vitamin D. Broken down further, 74% were below 20 ng/ml (50 nmol/L), and 19% had less than 10 ng/ml (25 nmol/L).
Schizophrenics were most likely to be severely deficient – 34% of them fell into the lowest bracket compared with 9% of the rest. Bi-polar sufferers, whilst still deficient at 19.8 ng/ml, had the highest average vitamin D levels in the sample.
“The observed prevalence of vitamin D deficiency in our psychiatric inpatient population supports the idea that supplementation should be more generally available, and perhaps routinely prescribed, given its low cost, lack of adverse effects and multiple potential benefits,” Menkes wrote in the study.[2]
An American study has reported similar results. Of 104 adolescents receiving acute mental health treatment, 34% had less than 20 ng/ml of vitamin D in their blood, 38% were sub-optimal (between 20 ng/ml and 30 ng/ml), with 28% normal.
Adolescents with psychotic behaviour were three and a half times more likely to be in the lowest vitamin D range.
“Vitamin D deficiency and insufficiency are both highly prevalent in adolescents with severe mental illness,” they concluded.[3]
[1] “Treating vitamin D deficiency may improve depression among women,” Allison Cerra, DrugstoreNews, www.drugstorenews.com/article/treating-vitamin-d-deficiency-may-improve-depression-among-women
[2] “Vitamin D status of psychiatric inpatients in New Zealand’s Waikato region,” Menkes et al, BMC Psychiatry, June 2012, BMC Psychiatry 2012, 12:68 doi:10.1186/1471-244X-12-68 http://www.biomedcentral.com/content/pdf/1471-244X-12-68.pdf
[3] “Vitamin D and psychotic features in mentally-ill adolescents – a cross sectional study,” Gracious et al, BMC Psychiatry 2012, 12:38
CHAPTER 11
MULTIPLE SCLEROSIS
“There is strong evidence that vitamin D concentrations during late adolescence and young adulthood have a major effect in determining MS risk”
– Lancet Neurology, 2010
For a long time, it’s been known that the number of multiple sclerosis cases grows the further north or south of the equator you go. The disease, as it progresses, causes people increasing amounts of discomfort and pain as they undergo nerve damage. Sufferers live, on average, five to ten years less. In my experience it’s worse than that: Fiona, a New Zealand TV colleague of mine, sister of a Hollywood movie director, passed away July 2012 after a long battle with MS – she’d been diagnosed in the early 1990s as I recall, when we were working together. She was only 50.
Fiona’s story is not unique. She was one of millions of sufferers worldwide. Scotland has the highest per capita rate of the disease, with one in 500 people affected.
It’s a neurological disease, resulting from the decay of myelin, a protective fatty sheath found around axons in the brain and spinal cord. Myelin helps nerves send messages across the body, so when it breaks down it’s like the blue screen of death on a computer; your system slowly starts to malfunction, more and more often. In the early stages the discomfort can be mild tingling, but by the end it can be blindness, paralysis and death.
With a clear north-south spread, it didn’t take long for researchers to pose the obvious question: is multiple sclerosis caused by a lack of vitamin D?[1]
For a start, the disease – like mental illness – can be tied back to the season of birth. Northern hemisphere sufferers are more likely to have been born around May, and least likely to have been born in November – the same season variation as that for depression.[2]
A 2006 study of US servicemen, based on routine blood samples taken and then comparing the results to later diagnoses, found a massive drop in multiple sclerosis cases the higher the vitamin D blood levels were.
Because of their jobs as active service personnel, the sample already had higher than average vitamin D levels.
For example, the lowest 20% had vitamin D below 63.3 nmol/L (25.3 ng/ml), which is a much healthier bottom quintile than psychiatric patients enjoy, for example.
Nonetheless, the US study found service personnel with the highest levels, above 99 nmol/L (39.6 ng/L) reduced their risk of developing MS by 62%.[3]
Another study found children who played longer outside each day during summer, between the ages of 6 and 15, lowered their risk of developing multiple sclerosis by an incredible 69%. The researchers found it was even more important to ensure children got sun exposure in winter as well – another clue that vitamin D was a big player.[4]
Dermatologists and skin specialists might hate the idea, but the researchers independently discovered that people with higher skin damage from sunbathing were far less likely to contract multiple sclerosis than peaches and cream wallflowers – a 68% lower risk.
For children who develop multiple sclerosis, their vitamin D status has been shown to have a big impact on the intervals between relapses. For every 10 ng/ml that they increase their blood levels by, their risk of a relapse dropped by 34% in one American study.[5]
Mothers who drink more D-fortified milk during pregnancy have been shown to reduce the risk of multiple sclerosis in their children by 43%.[6]
All of the attention on vitamin D makes sense now, in the light of the latest major study to be released. Scientists at Oxford have found what they believe to be a “leading cause for multiple sclerosis”, and it turns out to be a gene that causes vitamin D deficiency.[7]
“The study examined the DNA of a group of people with multiple sclerosis who also have a large number of family members with the disease,” says Christina Galbraith, a spokeswoman for the Jeffrey Epstein VI Foundation that part-funded the Oxford research with the Multiple Sclerosis Society.
“All the DNA samples showed a distortion of the CYP27B1 gene which controls vitamin D levels in the body.
“Despite this pivotal link, not all people with vitamin D deficiency develop multiple sclerosis…however, a distortion of the CYP27B1 gene is increasingly apparent in MS cases and it’s possible that the gene generates other, yet undetected, complications that lead to the disease.”
This, of course, reinforces the argument you’ve met repeatedly in this book, that whilst there may be environmental trigger points for various diseases – straws that break the camel’s back – the camel is more vulnerable to those triggers because of a lack of vitamin D in the first place.
In the case of multiple sclerosis, it might be that some people develop it because of a simple lack of vitamin D and the introduction of a trigger, while others may develop it because their genes don’t allow them to process vitamin D properly, thus also leaving them vulnerable when a trigger comes along. Treatment and prevention for each group might involve different strategies.
In the meantime, researchers say the evidence is almost overwhelming, and it’s time for serious trials to get underway:
“Vitamin D supplementation in healthy individuals is emerging as a promising approach for MS prevention. In utero and early-life exposure could also be important, but there is strong evidence that vitamin D concentrations during late adolescence and young adulthood have a major effect in determining MS risk. [8]
“On the basis of the results of the only longitudinal study of serum 25-hydroxyvitamin D and MS onset,[9] and assuming that these results are unbiased and vitamin D is truly protective against MS, over 70% of MS cases in the USA and Europe could be prevented by increasing the serum 25-hydroxyvitamin D concentration of adolescents and young adults to above 100 nmol/L.[10] These concentrations are commonly found only in individuals with outdoor lifestyles in sunny regions, but could be reached in most people by taking 1000–4000 IU cholecalciferol daily.[11]
“Whereas future observational epidemiological studies, and genetic and molecular investigations, will be useful to strengthen and refine the hypothesis, evidence is approaching equipoise,[12] at which the soundest decision might be to do a large randomised trial to establish the safety and efficacy needed to promote large-scale vitamin D supplementation.
“Although substantial evidence supports the safety of even large doses of vitamin D, such evidence is based on studies of limited size and duration, which were mostly done in older adults. A test of the hypothesis that vitamin D could reduce MS risk will require the administration of relatively high doses of vitamin D to hundreds of thousands of young adults for several years, and careful monitoring for unforeseen adverse effects is mandatory.
“Given the financial, logistical, and scientific complexity, and the limited societal experience with largescale population experiments, we suggest that an international multi-disciplinary working group should be set up to oversee the design of future prevention or supplementation studies.”
For researchers to state they are reaching “equipoise” on multiple sclerosis prevention is a major development, and not taken lightly. One of those human trials has just got underway in New Zealand and Australia – too late to save my colleague Fiona but not too late to save others.
This four year study, PrevANZ, is testing doses of vitamin D at three different levels – 1000IU daily, 5,000IU and 10,000IU, as well as placebo. Two hundred and ninety people who have experienced their first bout of the neurological precursor to MS, known as “clinically isolated syndrome”, are taking part. Researchers will analyse the doses for safety over the four years, as well as whether they reduce relapses and reduce MS lesions that are visible in MRI scans.
The choice for readers is whether to wait four years to find out, or whether to now take a high dose of vitamin D daily after talking to your doctor, on the grounds of promoting great bone health, and on the offchance that the researchers are absolutely right about the protective effect of vitamin D.
Those most at risk of deficiency-related MS are teenagers and young adults.
[1] The first scientific study to ask this question was in 1974: Goldberg P. Multiple sclerosis: vitamin D and calcium as environmental determinants of prevalence (a viewpoint). Part 1: sunlight, dietary factors and epidemiology. Intern J Environ Stud 1974; 6: 19–27.
[2] “Timing of birth and risk of multiple sclerosis: population based study,” Willer et al, BMJ. 2005 January 15; 330(7483): 120. doi: 10.1136/bmj.38301.686030.63
[3] “Serum 25-Hydroxyvitamin D Levels and Risk of Multiple Sclerosis,” Munger et al, Journal of the American Medical Association, JAMA. 2006;296(23):2832-2838. doi:10.1001/jama.296.23.2832
[4] “Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study,” van der Mei et al, British Medical Journal, 2003 August 9; 327(7410): 316. doi: 10.1136/bmj.327.7410.316, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC169645/
[5] “Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis,” Mowry et al, Annals of Neurology, Volume 67, Issue 5, pages 618–624, May 2010
[6] “Gestational vitamin D and the risk of multiple sclerosis in offspring,” Mirzaei et al, Annals of Neurology, Volume 70, Issue 1, pages 30–40, July 2011
[7] “A genetic cause for multiple sclerosis is identified and funded by science patron Jeffrey Epstein,” news release, 16 June 2012, www.jeffreyepsteinfoundation.com
[8] “Vitamin D and multiple sclerosis: a review,” Ascherio et al, Lancet Neurol 2010; 9: 599–612, http://66.160.145.48/seaton/pdfs/27/Ascherio_2010.pdf
[9] “Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis,” Munger et al. JAMA 2006; 296: 2832–38.
[10] “Vitamin D deficiency: a worldwide problem with health consequences,” Holick et al, Am J Clin Nutr 2008; 87 (suppl): 1080S–86S. See also “Vitamin D deficiency: a global perspective, Prentice A. Nutr Rev 2008; 66 (suppl 2): S153–64.
[11] Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr 2005; 135: 317–22.
See also “Human seru
m 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol,” Heaney et al, Am J Clin Nutr 2003; 77: 204–10.
[12] The point at which medical researchers believe they have found the most successful treatment for a given condition and which they believe they are ethically-bound to make known and put into formal testing.
CHAPTER 12
CHROHN’S DISEASE & TYPE 1 DIABETES
“Women with low vitamin D levels while pregnant have double the risk of giving birth to a diabetic child, when compared with mothers whose vitamin D levels were high”
– Diabetes, 2012
Yet another disease with a north-south gradient is Crohn’s Disease, a debilitating autoimmune disorder of the bowel and gut that sees the body attack itself. Although people aged 15-35 are the most vulnerable, no one is safe and another age band it targets are fifty to seventy year olds.
Like MS, around one in 500 people are affected by it, and just like MS and virtually every other illness you’ve read about in this book, there’s an inverse relationship between vitamin D status and risk of Crohn’s or its other form, ulcerative colitis.
A study in the US found women aged 40+ with the highest levels of vitamin D in their blood (above 32 ng/ml or 80 nmol/L), reduced their chance of suffering Crohn’s by 62%.[1]
It’s long been known that people with Crohn’s have particularly low vitamin D levels, so a couple of recent randomised controlled trials have tested vitamin D supplements on patients to see if they could stave off relapses.
A 2010 study gave 94 people either 1200IU of D3 a day or a placebo for a period of a year. All of them had Crohn’s, and all were presently in a remission phase. The goal of the study was to find out which group lasted longest in remission.[2]
Twenty-nine percent of the placebo group relapsed within a year. Only 13 percent of the vitamin D3 group relapsed in that time, effectively a risk reduction of almost 70% – more than two thirds.