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Posted by Ron Kennedy, M.D., Santa Rosa, CA

The Tuskegee Experiment

Vitamin D Newsletter
7/17/05

This is a periodic newsletter from the Vitamin D Council. If you don't want to get it, hit reply and let us know. This newsletter is not copyrighted. Please feel free to reproduce it or post it on internet sites.

Birth defects

Nothing frightens an expectant mother like the fear her baby will be deformed. Even worse, is the fear that a pill she took, or didn't take, caused a birth defect. The government requires drug companies give large doses of drugs to pregnant rats and then carefully examine the baby rats for evidence of birth defects. Drugs that cause birth defects in rats are either banned or controlled. The U.S. government doesn’t wait to see if the drug causes human birth defects, they rely on animal studies.

The lack of essential nutrients, such as folic acid, also causes birth defects. Scientists first discovered this in the 1960’s, again by studying rats. In 1992, the government finally took steps to prevent it by recommending supplementary folic acid for pregnant women. In 1996, the government ordered food manufacturers to fortify cereal grains with folic acid. Severe brain damage due to folic acid deficiencies fell significantly.

Birth Defects Res A Clin Mol Teratol. 2004 Nov;70(11):844-5

Vitamin D deficiency and brain damage

Australian researchers, led by Professor John McGrath and Dr. Darryl Eyles, recently discovered that severe maternal vitamin D deficiency permanently damages the brains of baby rats. Giving extra vitamin D to the newborn rats will not reverse the damage. Noting that vitamin D deficiency is common in young women, the authors speculated that “optimizing vitamin D levels in pregnant women and neonates may reduce the incidence of certain neurological and neuropsychiatric disorders.”

Neuroscience.2003;118(3):641-53

Brain Res Bull. 2005 Mar 15;65(2):141-8

After Australian scientists found birth defects in the baby rats, Professor Axel Becker and his German colleagues confirmed that even transient vitamin D deficiency leads to subtle changes in rat behavior. Slightly enlarged ventricles, cortical aberrancies, and reduced nerve growth factors (compounds essential for the billions of connections in mammalian brains) were only some of the birth defects. Such deformities, were they to occur in the more complex human brain, should have significant and lifelong consequences on learning, memory and IQ. The Australian scientists concluded, “Given the fact that vitamin D deficiency is more common than previously thought, the public health implications for the developing foetus cannot be ignored.”

Behav Brain Res. 2005 Jun 20;161(2):306-12

Brain Res Dev Brain Res. 2004 Oct 15;153(1):61-8

Behav Brain Res. 2004 Oct 5;154(2):549-55

Does maternal vitamin D deficiency cause learning disabilities?

To date, no human studies exist to corroborate these animal studies. Or, do they? If vitamin D deficiency causes brain damage, then we can make certain predictions based on things we know about vitamin D. First, we know that at temperate latitudes, maternal vitamin D levels are lowest in the winter and early spring when the lack of sun means the skin makes little or no vitamin D. Second, we know vitamin D levels are lower among blacks than whites because melanin pigment in skin acts as an effective sunscreen for casual sun-exposure.

If maternal vitamin D deficiency causes fetal brain damage, more brain-damaged children will be born in the summer. (This will be true at temperate latitudes, but not in the tropics where the sun makes vitamin D year-round). Brains of summer-born children are making neuronal connections at the fastest rate during the winter and early spring when their mother’s vitamin D levels are lowest. If vitamin D deficiency damaged human brains, then summer-born children should be retained more often, do worse in school, and display more learning disabilities.

At latitude 42 degrees, Boston, Massachusetts has a marked seasonal variation in 25(OH) vitamin D levels. Dr. Nathlie Badian of Harvard found that boys born in July and August were seven times more likely to have learning disabilities than those born in the cooler months. In her study, the summer students were not the youngest - the fall students were the youngest -and yet the fall-born students had much less disability than the summer-born children.

J Learn Disabil. 1984 Mar;17(3):129-36

Northeastern Georgia also has significant seasonal variations in 25(OH) vitamin D levels. Dr. Roy Martin of the University of Georgia recently reviewed the literature and conducted his own study as well. He found, “children born from June through August were more frequently retained, performed lower on standardized tests, and were more frequently diagnosed with specific learning disabilities.” Martin added, “The overall effect on the children born June through August was enormous.”

J Learn Disabil. 2004 Jul-Aug;37(4):307-17

In tropical Hawaii, which should have much less seasonal variation in 25(OH) vitamin D levels, Dr. Grace Diamond found, as expected, that the youngest students had higher rates of disabilities. However, unlike Georgia or Boston, she found no evidence of excessive learning disabilities in summer-born Hawaiian children. Such latitudinal variation in the incidence of learning disabilities in summer born children suggests maternal vitamin D deficiency may cause learning disabilities.

J Learn Disabil. 1983 Mar;16(3):161-4

Dyslexia, poor school attendance, low Apgar scores, and low birth weight

Some studies show summer born children are also more likely to suffer from dyslexia and poor school attendance. Dr. Richard Livingston, of the University of Arkansas Medical School, found, “the risk of dyslexia among children born in May, June, or July is more than double that for those born in other months.” Pregnant women exposed to the lowest temperatures in the second trimester (and thus the least vitamin D) have infants with lower birth weights.

J Am Acad Child Adolesc Psychiatry. 1993 May;32(3):612-6

Br J Educ Psychol. 1992 Nov;62 ( Pt 3):391-6

Aust N Z J Obstet Gynaecol. 2004 Dec;44(6):553-7

A particular type of schizophrenia, called deficit schizophrenia, has consistently been found to be more common in summer-born patients. Patients with deficit schizophrenia have a poor prognosis and display more evidence of brain damage than other patients with schizophrenia display.

J Nerv Ment Dis. 2001 Sep;189(9):608-12

Am J Psychiatry. 1998 Sep;155(9):1221-6

Am J Psychiatry. 2002 Aug;159(8):1382-7

African Americans are at much higher risk

If maternal vitamin D deficiency causes brain damage, then blacks will be more affected than whites. Vitamin D deficiency discriminates based on race. The darker a mother’s skin, the lower her 25(OH) vitamin D level, and the less vitamin D is available to help her baby develop. Numerous studies document that black mothers are more likely to give birth to infants who weigh less and die shortly after birth. Black babies also have lower Apgar scores and black children have higher rates of mild mental retardation.

Biol Res Nurs. 2005 Jul;7(1):55-66

Pediatrics.2003 Jan;111(1):e61-6

Paediatr Perinat Epidemiol. 1999 Apr;13(2):205-17

Pediatrics.1998 Jan;101(1 Pt 1):77-81

Am J Public Health. 1995 Mar;85(3):324-8

This newsletter will not delve into the hundreds of other studies showing dramatic academic differences between black and white children, or the charges of racism that inexorably follow any such discussion. Obviously, any suggestions that black babies are more likely to be born brain damaged have profound political implications. Remember. We are not talking about genetics. We are talking about a modifiable risk factor, a natural, safe, supplement costing pennies a day: simply treating pregnant women who are vitamin D deficient.

Severe vitamin D deficiency twenty times more common in young black women

In 2002, U.S. government scientists at the Centers for Disease Control reported that severe vitamin D deficiency is 24 times more common among young African American women than young white women. Dr. Shanna Nesby-O’Dell and her colleagues at the CDC found that blood levels were much lower in young black women than young white women. Almost 50% of young black women had levels < 15 ng/ml. (Remember that most vitamin D experts recommend levels above 40 ng/ml). Most frightening of all, 12 percent of young black women had levels < 10 ng/ml (compared to ½ of 1 percent of white women). Levels that low approach those seen in mother rats that give birth to brain damaged babies. It may be that white children have a huge developmental advantage over black children, an advantage that begins at conception.

Am J Clin Nutr. 2002 Jul;76(1):187-92

We do not know if maternal vitamin D deficiency damages human brains like it does rat brains. We do know young children with the least supplemental vitamin D are at a five-fold higher risk for developing type 1 diabetes later in life. Male children with the least supplemental vitamin D also suffer a similar risk for developing schizophrenia later in life. Now it appears possible that children with the lowest amount of vitamin D during critical fetal development suffer irreversible brain damage.

Lancet.2001 Nov 3;358(9292):1500-3

Schizophr Res. 2004 Apr 1;67(2-3):237-45

How much vitamin D do women need to prevent vitamin D deficiency during pregnancy? About ten times more than the government recommends, according to Professors Bruce Hollis and Carol Wagner of the Medical University of South Carolina. How much do pregnant black women need? A lot more than whites, say Hollis and Wagner. These experts find the government's recommendation of 400 units a day for pregnant black women is essentially meaningless; such amounts do not raise blood levels in pregnant women. In other words, the government’s current recommendations for pregnant black women are roughly equivalent to doing nothing. Pregnant women of all races should keep 25(OH) vitamin D levels around 40 ng/ml throughout pregnancy. Hollis and Wagner find it takes up to 4,000 units a day, ten times the government’s recommendation.

Am J Clin Nutr. 2004 May;79(5):717-26

Am J Clin Nutr. 2004 Dec;80(6 Suppl):1752S-8S

Government inaction: incompetence or indifference

For forty years, from 1932 to 1972, the U.S. government experimented on 399 black men in Tuskegee, Alabama. The government knew - from studying experimental rabbits - that syphilis can progress and cause terrible damage, including permanent brain damage. However, the government didn't exactly know how syphilis affected African Americans. The prevalent theory in 1932 was that blacks would suffer less brain damage than whites. Government doctors said they wanted more data. So they withheld treatment, even after penicillin was discovered and found to be effective. The government doctors simply followed the men, carefully studying them to find out if syphilis damaged black brains as much as it did rabbit brains.

Remembering Tuskegee

The Tuskegee Syphilis Experiment

This newsletter is not contending that the U.S. government is repeating the abominable experiments of Tuskegee. There is a great difference between using blacks as guinea pigs and doing nothing. Today, the government is simply doing nothing. They will tell you they need more studies about maternal vitamin D deficiency, and we do. There is not question that more research is needed. The question is: what should we do in the meantime?

If we do nothing, we are in effect continuing this Kafkaesque natural experiment on pregnant black women and the brains of their unborn children. The choice is either doing nothing while we conduct more studies, or treating vitamin D deficiency in pregnancy while we conduct more studies. The risk of doing nothing is great (as with syphilis) while the risk of treating vitamin D deficiency in pregnancy is minimal (much safer than penicillin).

Seventy years ago, the government had reason to think penicillin would help syphilis because studies on experimental rabbits demonstrated its effectiveness. More recently, the government started supplementing young women with folate to prevent brain-damaged babies after animal studies and clinical trials demonstrated its effectiveness. Now the government knows animal studies show severe maternal vitamin D deficiency causes fetal brain damage. The government also knows 12 percent of young black women in the United States are severely vitamin D deficient, compared to only one-half of 1 percent of young white women.

If rat studies showed a drug damages brains like maternal vitamin D deficiency damages brains, the government would immediately ban the drug. The Australian scientists plead with the government, saying their research “cannot be ignored.” Perhaps the Australians don’t know how the U.S. government ignored the suffering of black men is Tuskegee Alabama. Will the government again do nothing but wait to see if African Americans suffer? Will the U.S. government simply call for more studies as we all wait to see if maternal vitamin D deficiency damages black brains like it does rat brains?

Another Vitamin D Quiz

This month we have a ten question quiz on the latest vitamin D research. Here’s a primer.

To demonstrate the point, I recently swallowed an entire bottle (100 capsules) of vitamin D (40,000 units) in front of a skeptical audience to convince them that vitamin D is safer than water. Here’s why. Eight glasses of water a day is fine for healthy adults. Ten times that amount, eighty glasses of water, will make you sick from water intoxication.

Humans need about 4,000 units of vitamin D a day (from all sources). Ten times that amount, 40,000 units, is very safe in a single dose, as I demonstrated to the audience. Therefore, vitamin D has a safer therapeutic index than water.

(Taking the entire bottle certainly got the audience’s attention. I think they were paying close attention to see if I would drop dead. By the way, if you were to take 40,000 units every day for months you would get vitamin D toxicity, after years of such doses you would probably die. After taking 40,000 units at one time - equivalent to two days at the beach - I simply stayed out of the sun for several days.)

Why do we need vitamin D? Within the last several months, scientists published impressive new evidence that vitamin D is involved in a staggering array of diseases: age related cognitive decline, heart disease, breast cancer, tuberculosis, Parkinson’s disease, prostate cancer, chronic pain, fractured hips, premenstrual syndrome and diabetes.

Good time for another quiz.

1. Vitamin D reverses inflammatory changes associated with age-related memory impairment.

  1. True
  2. False

True. Researchers from Ireland were the first to demonstrate that vitamin D3 acts as an anti-inflammatory agent and turns old brains into young brains - at least as far as inflammatory cytokines are concerned. This research suggests vitamin D may prevent, or even treat, age-related cognitive decline!

Biochem Soc Trans. 2005 Aug;33(Pt 4):573-7.

2. Your blood sugar is closely associated with your vitamin D level.

  1. True
  2. False

True. Researchers in Australia added to the growing evidence that sun avoidance may have caused the epidemic of type 2 diabetes. The Australians’ findings were straightforward and powerful. The higher your vitamin D level, the lower your blood glucose.

Clin Endocrinol (Oxf). 2005 Jun;62(6):738-41.

3. In July, a group from Minnesota found that 100% of elderly patients admitted for fragility fractures were vitamin D deficient despite the fact that half of them were taking vitamin D supplements.

  1. True
  2. False

True. The authors found that women taking supplemental vitamin D had average levels of 16.4 ng/ml while women not taking supplements had levels of 11.9.ng/ml, both dangerously low. None of the 82 women got enough sun or took enough vitamin D to obtain a level of 40 ng/ml. These were fragility fractures, not fractures caused by unusual trauma. That is, their bones just sort of fell apart.

Curr Med Res Opin. 2005 Jul;21(7):1069-74.

4. Women with the lowest vitamin D levels had five times higher risk for breast cancer.

  1. True
  2. False

True. Women with 25(OH)-vitamin D blood levels less than 20 ng/ml were more than five times more likely to be diagnosed with breast cancer than were women with levels above 60 ng/ml. That is five, repeat five, times less likely!

Eur J Cancer. 2005 May;41(8):1164-9. Epub 2005 Apr 14.

5. Avoiding the sun doubles the risk of prostate cancer.

  1. True
  2. False

True. Again, the risk of avoiding the sun is clear, this time in another study with prostate cancer. However, the authors pointed out that sun exposure increases the risk of skin cancer and believed that proper vitamin D supplementation ”may be the safest solution to achieve an adequate vitamin D status.”

Cancer Res. 2005 Jun 15;65(12):5470-9.

I also believe supplementation is the only way to go for many people. African Americans are simply unable spend adequate time in the sun. In addition, the sun ages the skin and that fact alone will keep many Americans out of the sun. That said, I go into the sun whenever I can. The reason is simple: it is the most conservative thing to do. Until we know everything the sun does - and it does more than just make vitamin D - the conservative approach is to mimic our ancestors and the environment in which human evolved, whenever we can. Therefore, it makes sense to sunbathe sensibly in the late spring, summer, and early fall and take supplements or use UVB lamps the rest of the time.

6. South Korean researchers associated vitamin D deficiency with Parkinson’s Disease.

  1. True
  2. False

True. Actually, they showed that certain genetic malformations (VDR polymorphisms) are more likely in-patients with Parkinson’s Disease, implying an association with vitamin D and Parkinsonism.

J Korean Med Sci. 2005 Jun;20(3):495-8.

7. Researchers in England discovered that patients with chronic pain have phenomenally low vitamin D levels.

  1. True
  2. False

True. The authors added to the evidence that severe vitamin D deficiency is associated with chronic pain. They found that 88% of their patients with chronic pain had levels less than 10 ng/ml. If they treated their patients, they did not report it. However, Swiss researchers recently treated chronic pain patients with vitamin D and reported the pain “disappeared” within one to three months in most of their patients. This is the second open study that showed adequate doses of vitamin D dramatically improve chronic pain.

Ann Rheum Dis. 2005 Aug;64(8):1217-9.

BMJ. 2004 Jul 17;329(7458):156-7.

Spine. 2003 Jan 15;28(2):177-9.

8. Severe vitamin D deficiency is common in TB patients.

Some English doctors don’t the difference between ideal and “normal” levels.

Most American doctors don’t know the difference either.

  1. All are true
  2. All are false
  3. Some are true and some are false

All are true. First, the authors reviewed the impressive animal evidence that vitamin D can help treat TB. Then they reported that most of their immigrant TB patients had undetectable vitamin D levels. Then they reported the normal range for their lab was between 5 to 47 ng/ml but “normal” was any level greater than 9 ng/ml. Finally, the researchers reported they treated their patients with “normal daily doses” of vitamin D, without reporting how much they gave. Apparently, they gave just enough to get patients above 9 ng/ml.

J Infect. 2005 Jun;50(5):432-7.

Keep in mind that different laboratory technique result in different ranges for 25(OH)-vitamin D levels. Now matter what technique is used, ideal levels can roughly be defined as any level above the median. In this case, as you will see below in Dr. Heaney’s article, the doctors should have treated their patients with 4,000 units a day. They should also watch for evidence of vitamin D hypersensitivity, which can occur when treating tuberculosis patients for vitamin D deficiency.

We can only mourn for the poor immigrants who have to suffer from both TB and vitamin D deficiency. Of course, few physicians in the USA know the difference between the Gaussian definition of “normal” (average ranges for the population tested) and the ideal definition of “normal” (levels above 32 ng/ml). Getting commercial reference labs to report ideal 25(OH)-vitamin D levels should be a priority of everyone involved in trying to end the epidemic of vitamin D deficiency.

9. Virtually all nephrologists give renal failure patients a vitamin D-like drug.

Virtually all renal failure patients are severely vitamin D deficient.

Some nephrologists know the difference between vitamin D and calcitriol.

  1. All are true
  2. All are false
  3. Some are true and some are false

All are true. Finally, the truth about renal failure patients: most of them are vitamin D deficient despite taking vitamin D analogs! Most nephrologists prescribe activated vitamin D (calcitriol) or vitamin D analogs but not vitamin D. Calcitriol and vitamin D analogs do nothing to prevent vitamin D deficiency. Renal failure patients need both vitamin D and a calcitriol-like drug. Moreover, 400 units a day of vitamin D will not correct their deficiencies. As you will see below, they need up to 4,000.

Am J Kidney Dis. 2005 Jun;45(6):1026-33.

P.S. If you think nephrologists know the difference between vitamin D and calcitriol, read this months paper from some nephrologists at the University of Texas. They discuss the importance of vitamin D in preventing and treating heart disease. (I think adequate vitamin D nutrition may prevent more cardiovascular deaths than cancer deaths.) However, I read the Texas paper three times and still don’t know if the authors know the difference between vitamin D and calcitriol. I hope they know the difference between cholesterol and testosterone. (Some cholesterol is metabolized into steroid hormones, vitamin D is a prehormone; testosterone is a steroid hormone, calcitriol is the most potent steroid hormone in the human body).

Kidney Int Suppl. 2005 Jun;(95):S37-42.

10. Professor Robert Heaney proved, again, that he is a gentleman and a scholar.
  1. True
  2. False

True. In the most important clinical paper published this month, Heaney gave the three best reasons why we should all maintain minimum levels of at least 32 ng/ml, the level that:

  1. effectively suppresses PTH,
  2. maximizes calcium absorption,
  3. maximally improves glucose tolerance.

Then he goes on to show that some of us, especially African Americans, will need to take 3,000 to 4,000 units every day to maintain healthy 25(OH)-vitamin D blood levels.

J Steroid Biochem Mol Biol. 2005 Jul 15.

He then defends the Institute of Medicine’s (IOM) recommendation that we only take one-tenth that amount as the best science that was available in 1997. I admire Dr. Heaney for trying to cover for the IOM. The truth is that both Dr. Heaney and Dr. Holick told the IOM that 2,000 units a day was not toxic and would prevent both adequate treatment and meaningful research. The IOM then proceeded to ignore the only two vitamin D experts on the panel.

Writing two years later, Professor Reinhold Vieth came up with dozens of studies the IOM overlooked. These studies conclusively showed 2,000 units a day could not be toxic. Furthermore, Vieth found the literature published before 1997 clearly showed 10,000 units a day was unlikely to be toxic. Vitamin D toxicity probably starts around 20,000 units a day, and then only if taken for months or even years.

Am J Clin Nutr. 1999 May;69(5):842-56.

This is a periodic newsletter from the Vitamin D Council. If you don't want to get it, hit reply and let us know. This newsletter is not copyrighted. Please feel free to reproduce it or post it on internet sites.



The information in this article is not meant to be medical advice.�Treatment for a medical condition should come at the recommendation of your personal physician.

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