Vitamin D: SEX AND SURVIVAL

One the largest full moon will be observed next Friday night, it's reported. I still can't get wolves off my mind...esp since my children and I are completely mesmerized by the Planet Earth DVD series right now. One of my daughters was born in August -- the busiest time of the year for most OB/GYN/maternity wards around the country. As you know, we celebrated our first Paleo b-day party for her this year. Apparently she is hardly alone in celebrating a birthday in this month! In the U.S., August is the month with the highest birth rates according to a report by ABC News (we concur -- nearly got kicked out and diverted to another hospital the night of the impending birth since all the beds were full -- luckily one opened up *wink*):
Summertime Mystery: More Born, Less Die in August

If human mammals have 40-week gestation periods (10-lunar months) and you do the math....there are a lot of us participating in uuuummm...reproductive activities during this month of cheer, festivities, and mirth, December. How is Vitamin D vital to some of these uuummm 'processes' do you ever wonder?

Are we so different from wolves and bears? Obviously we are different species (bears, 38 chromosomes; wolves, 39; humans, 23) however hormonally we are very very similar:
--melatonin (from the pineal gland)
--testosterone
--estrogen
--progesterone (the 'pregnancy' hormone)
--vitamin D (sourced from sun and rich salmon catches; IDEAL: 60-70s ng/ml)
--PTH (breaks down bone to modulate blood calcium, esp when vitamin D is low; IDEAL PTH levels imo 10-20)
--thyroid hormones T3 T4 and related TRH (thyrotropin-releasing hormone) and TSH (thyrotropin)




Sex Hormones in Black Bears

Researchers of black bears compared sex hormone concentrations between between summer and winter seasons as well as pregnant v. non-pregnant bears. Guess what 3 things they discovered?

• "We found that serum sex steroids measured in black and polar bears change independent of torpor. Therefore, our results suggest that photoperiod may be a more important regulator of serum steroid levels and reproduction than metabolic condition." (Bahr JM (no joke on the name) et al Biol Reprod. 1988 Jun;38(5):1044-50.)


• "During starvation in summer, the bears could not inhibit the net production of urea but used lean body mass...The ability to preserve lean body mass during winter sleep apparently is a special mechanism associated with the induction of winter sleep. Bears cannot duplicate this feat during summertime starvation. In winter sleep, urea is formed and degraded but the nitrogen produced is conserved in some manner that maintains the total nitrogen pool constant....Arginase activity in liver increased in winter sleep; hepatic steatosis and inflammatory reactions were also noted." (Code CF et al. Mayo Clin Proc. 1975 Mar;50(3):141-6.)


• "During winter sleep the black bear has decreased levels of serum total and free thyroxine (T4) and triiodothyronine (T3) and a prolonged, delayed response of serum thyrotropin (TSH) (bioassay) to thyrotropin-releasing hormone (TRH). Four weeks after the end of winter sleep, levels of serum thyroid hormones increase, and TSH response to TRH is short and brisk. Serum T4 and T3 rise after TRH administration both during and after winter sleep; however, the maximum increment in serum T3 is greater during winter sleep when the TSH rise is also prolonged and exaggerated. These observations suggest that transient hypothyroidism of possible hypothalamic origin occurs in bears during winter sleep." Nelson RA et al Effect of winter sleep on pituitary-thyroid axis in American black bear. Am J Physiol. 1979 Sep;237(3):E227-30.

Seasonality, Sex and Survival

The length of the day (photoperiod) triggers activation of Thyroid hormone in both the hypothalamus and the pituitary glands in the birds and the bees...well...specifically QUAILS as demonstrated in the latest scientific breakthrough in Nature (below). The same research group shows a similar outcome in mice...here in the prestigious PNAS Nov 2008.

• Thyrotrophin in the pars tuberalis (PITUITARY) triggers photoperiodic response. "Molecular mechanisms regulating animal seasonal breeding in response to changing photoperiod are not well understood... Here we show cascades of gene expression in the quail MBH (hypothalamus) associated with the initiation of photoinduced secretion (read: UVB sunlight which also triggers vitamin D synthesis) of luteinizing hormone...Increased TSH in the pars tuberalis therefore seems to trigger long-day photoinduced seasonal breeding." Yoshimura T et al Nature. 2008 Mar 20;452(7185):317-22.

And yes in case you are wondering humans have VDRs (vitamin D receptors) all over the brain -- in the hypothalamus (McGrath JJ, J Chem Neuroanat 2005)and of course the pituitary (Diguez C Life Sci. 1997).

So what may signal an increase in Thyroid hormone in bears and humans? What extends the photoperiods and those warm, long, lazy summer days?

Did you know in humans, seasonality of Thyroid hormones are observed as they are in the above bear studies? HERE, HERE and HERE. The Pituitary-Thyroid-Hypothalamus-Gonad axis potently controls reproduction. I talk about the Pituitary and Hypothalamus a lot because these are the endocrine glands which produce the signals that impact the sex organs (gonads) to produce Estrogen, Progesterone, DHEA, Testosterone, etc. The sypmphony of hormone music is truly a monumental miracle -- all geared to produce one single event. Yes, it truly breaks down to one thing.

No...not the 'O'... silly, which aint a bad event...

Conception.

NON-IMMACULATE.

Survival of the species...

More and more trials and studies are coming out demonstrating how Vitamin D synergistically affects this awesome baby-making health axis.

Dr. Davis has now discussed how both the hormone of light (Vitamin D) and the hormone of darkness (Melatonin) controls and optimizes the cardiovascular system. Indeed, they actually optimize every system including the reproductive.



Degeneration Associated with Vitamin D Deficiency

The role of vitamin D to me appears central and pivotal for signalling mammalian bodies to prepare for reproduction/survival. By survival, I'm referring to survival of our lineage and paternal/maternal DNA. There are a few things non-conducive to that achievement...for instance, death is one. Death of either parent would diminish chances of passing on beneficial genes I would guess. Myocardial infarction or erectile dysfunction might be another. How is our survival linked to nutrients and optimization of survival? Dr. Bruce Ames has discussed the importance of achieving optimal levels of ALL micro- and macronutritients to prevent DNA damage and cancer here in his famous/infamous PNAS article (Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage.PNAS 2006 Nov 21;103(47):17589-94.); Magnesium deficiency accelerates cellular senescence in cultured human fibroblasts. Killilea DW et al. Proc Natl Acad Sci U S A. 2008). His research has shown that if even one nutrient (like, let's say folic acid) is omitted, DNA damage occurs in the lab animal just as if the lab animal sustained significant radiation damage. For heart disease, we at TYP understand the importance of obtaining nutrients for the benefits of reversal of atherosclerosis and plaque. This also absolutely extends to fertility and reproduction. I loved Dr. Schwalfenberg's organ review and the role of Vitamin D in every organ system HERE. Reproduction is one of the most important functions for survival (right?) and it was another organ system that unfortunately failed to get a mention (in addition to Parathyroid and Thyroid). So..."let's talk about S*X baby..." *wink*



Vitamin D From Sunlight

Do you feel sexier in the summer? High vitamin D (eg, long photoperiods/sunlight) appears to be correlated with high reproductive activities and characteristics which are conducive to reproduction, for example great skin/hair (estrogen), great muscles and physique (testosterone), amorous displays (testosterone) and libido (testosterone). Did you know that Vitamin D supplementation normalizes estrogen and testosterone (via aromatase)? In men with low testosterone, supplemenation can modulate and raise blood testosterone. In women, the same, with estrogen.

But let's be reasonable. Taking supplemental vitamin D is not going to make you an immortal god/goddess overnight.

But it will sure help.




Fertility and Survival

Both long-term survival (species) and short-term survival (individual) appear assured when both vitamin D and sex hormones are set within normal limits. At TYP, hormone replacement with vitamin D, bio-identical estrogen and testosterone have been shown to allow regression and eradication of plaque and heart disease successfully. Vitamin D of course is vital for reproductive health, and deficiency may have long-range survival consequences as we are finding out globally.

How many infertile couples do you know of? How many moms with PCOS (eg, wheat intolerance, insulin resistant, fish oil/vit D deficient) who can't naturally conceive? How many celebrity twins can you count being born annually? Or just the ones among your friends, family, acquaintenances and neighbors?



Vitamin D Deficiency Linked to Infertility, Low Sperm Counts, Maternal Pre-eclampsia, Pre-emies, and Premature Births, SIDS, Infant Mortality

FEMALE INFERTILITY AND MALE LOW SPERM COUNTS
Vitamin D is necessary for optimal health. Unfortunately the corollary is true and supported by the established and emerging medical literature. Deficiency leads to suboptimal health and particularly poor reproductive health...which translates to discontinuation of genetic information for some folks. At the end of October, researchers from Australia prospectively showed that Vitamin D supplementation increased sperm counts in infertile males. A year ago, my OB had told me about the use of Vitamin D in the fertility clinics to improve sperm counts. I couldn't find any prospective studies at the time and just forgot about it. Until now. It entirely makes sense to me.

Vitamin D Plays Major Role in Male InfertilityIn a paper presented to this week's Fertility Society of Australia conference (10/21/2008 reported here by ABC), Dr Anne Clark shows Vitamin D deficiency may play a major role in male infertility. Clark, medical director at the Fertility First assisted reproduction clinic in Sydney, says blood screening of 794 men who visited the unit found more than a third of them had vitamin D deficiency.

They were also found to be deficient in folate and had elevated levels of homocysteine, an amino acid in the blood associated with cell toxicity.
Among the couples where the male completed treatment for their nutritional deficiencies, just over half conceived naturally or with minimal treatment.

The finding comes out of a study by University of Sydney doctoral student Laura Thomson who is investigating DNA fragmentation of sperm, a significant factor in male infertility. DNA fragmentation of sperm is most often the result of cellular damage resulting from infection, smoking or advanced paternal age.

Clark says their findings add weight to a European study earlier this year that shows women's vitamin D levels strongly correlate with their ability to conceive.

Surprise"Vitamin D and folate deficiency are known to be associated with infertility in **women**, but the outcomes of the screening among men in our study group came as a complete surprise," she says.
She says concerns about skin cancer resulting from exposure to ultraviolet rays could be a contributing factor to vitamin D deficiency among men, along with work and lifestyle choices to avoid too much direct exposure to sunlight. "The amount of sun needed is just 10 to 15 minutes a day outside the heat of the day," she says. If workers had their morning tea break outside with their sleeves rolled up they would absorb sufficient vitamin D, Clark says. In response to the screening results, Clark says 123 of the men agreed to a program that included changes in lifestyle and diet such as quitting smoking, reducing caffeine and alcohol intake, and losing weight.

Results (sorry--couldn't find the paper -- don't know the vitamin D dose)
The men were also asked to take antioxidants and a multi-vitamin for two to three months, Clark says.
--She says the lifestyle changes led to a 75% reduction in the level of sperm fragmentation among the 123 men.
--"We also observed improvement in the shape of sperm, which can enhance conception," Clark says.
--Forty pregnancies had been achieved among the group, with more than half of those pregnancies occurring naturally or with minimal intervention such as intrauterine insemination.
--Clark says there were only three miscarriages (6%) among those pregnancies. This compares with an average 22% miscarriage rate among women using fertility treatment, she says.

Animal studies have long supported the important role of vitamin D in reproduction:

• Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads. In Vitamin D receptor null mutant mice, the aromatase activities in these mice were low in the ovary, testis, and epididymis at 24%, 58%, and 35% of the wild-type values, respectively. Seino Y et al Endocrinology. 2000 Apr;141(4):1317-24.
• 1,25-Dihydroxyvitamin D3 restores fertility of vitamin D-deficient female rats. Deluca HF et al Am J Physiol. 1989 Apr;256(4 Pt 1):E483-7.
• Vitamin D is necessary for reproductive functions of the male rat. Deluca HF et al J Nutr. 1989 May;119(5):741-4.
• Effect of vitamin D deficiency on fertility and reproductive capacity in the female rat. Deluca (the granddaddy of the 'D' in Wisconsin -- what is it with the water in Wisconsin and ground-breaking vitamin D science?!) discovered that when "Female weanling rats were maintained on either a vitamin D-replete or vitamin D-deficient diet until maturity and mated with normal males, Vitamin D-deficient females were capable of reproduction. However, vitamin D deficiency reduced overall fertility by 75%, diminished litter sizes by 30% and impaired neonatal growth from day 6 to day 15 of lactation. Fetal development asjudged by weight gain and viability appeared normal. Neonatal viability was also normal even though growth was retarded." J Nutr. 1980 Aug;110(8):1573-80.
• Reduced fecundity of vitamin D deficient rats. Researchers found that deficient rat-mothers produced babies with undetectable vitamin D levels as well as significantly few young. Woodward WD et al Comp Biochem Physiol A Comp Physiol. 1983;74(4):923-5.
• Effect of vitamin D repletion on testicular function in vitamin D-deficient rats. Singh PI et al Ann Nutr Metab. 1995;39(2):95-8.
• Seasonality in human reproduction: an update. Not a direct association -- of vitamin D and reproduction. The authors speculate "In northern countries, however, in regions where a strong seasonal contrast in luminosity exists, activity of the anterior pituary-ovarian axis and the conception rate are decreased during the dark winter months. In these areas, inversely, a peak in conception rate during summer leading to a maximum in birth rate in spring has been observed. It is believed that seasonality in the ovulation rate may cause this variability." Schenker JG et al Human Reproduction, Vol. 7, No. 6, pp. 735-745, 1992.
• Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcomes from human and animal studies. The author concludes that "the mother needs much higher doses (100 mug or 4000 IU per day) to achieve adult-normal 25(OH)D concentrations in her exclusively breastfed infant." Kovacs CS. Am J Clin Nutr. 2008 Aug;88(2):520S-528S.

MATERNAL PRE-ECLAMPSIA
Pre-eclampsia is on the rise...like vitamin D deficiency is. Connection? yes. Preventable? absolutely yes. Pre-ecampsia is a life-threatening condition leading to hypertension and early kidney damage in pregnant women usually presenting in the 2nd or 3rd trimester. BP drugs and strict bedrest (eg, not even getting out of bed to pee, no joke).


If vitamin D is a steroid and during pregnancy, the pregnant woman is making 10-TIMES more steroids to grow, sustain, and harbor a growing fetus, what do you think occurs if the mom starts out vitamin D deficient? Or what if she starts out critically vitamin D deficient -- like many women who abhor the sun for vanity (I may be part of this group *wink* and because I was deathly allergic to sun when I was wheat-addicted) and/or wear sunscreen and makeup...what might occur? Can you imagine what might occur as the mom's body starts to run out of the raw materials (cholesterol and vitamin D) to make estrogen, progesterone and oxytocin?

Not good things?

Pre-eclampsia, pregnany-related hypertension, proteinuria, kidney failure, and potential maternal and/or fetal death to name a few.

Fetal neurologic and autoimmune disorders.

Perhaps sowing the seeds for future heart disease? Perhaps the vitamin D deficiency of OUR mothers is currently affecting OUR generation? And future generations.

As we reviewed in the last post, vitamin D regulates our blood pressure by affecting the angiotension-renin-kidney system. Pre-eclampsia is basically a critical hormone and vitamin D imbalance.

• [Vitamin D deficiency in recently pregnant women] The authors enrolled n=89 pregnant and new moms and found 80% were vitamin D deficient with 25(OH)D less than 30 ng/ml (which means 99% were PROBABLY low less than 60 ng/ml). The scientists conclude that "Our data show that vitamin D supplementation of pregnant women (400 IU/day) is not enough and that 25VTD deficiency is not diagnosed in this high-risk population. Children born from deficient mothers will present a higher risk of suffering from bone mineral diseases as well as other pathologies, as type 1 diabetes or neurological disorders. Of course, this insufficiency will also have an impact on mother's bone reserve, but these mothers will also be at higher risk for preeclampsia." Emonts P et al. Rev Med Liege. 2008 Feb;63(2):87-91.


• Vitamin D deficiency in pregnant New Zealand women. "RESULTS: 87% of women had 25-hydroxy vitamin D levels below 50 nmol/L (20 ng/ml). 61.2% of women had a vitamin D level below 25 nmol/L consistent with severe vitamin D deficiency. 10 women had an elevated parathyroid hormone consistent with secondary hyperparathyroidism. Only 22% of our patients were veiled, and included a diverse ethnic population, including African, Maori, European, Middle Eastern, and Polynesian women. CONCLUSIONS: Vitamin D deficiency is common in young pregnant women in this general practice, and it was not only confined to veiled women or women with dark skin. This highlights the magnitude of vitamin D deficiency in the pregnant population in a New Zealand setting; this vitamin D deficiency is responsible for the re-emergence of childhood rickets." Eagleton C et al N Z Med J. 2006 Sep 8;119(1241):U2144.
• Pre-eclampsia: A challenge to public health teams worldwide to ensure that maternal diets contain adequate levels of folic acid, n3 polyunsaturated fatty acids and vitamin D at conception. Garratt FN.
  Public Health. 2008 Dec 4. [Epub ahead of print] No abstract available.
  PMID: 19058819 [PubMed - as supplied by publisher]
• Does vitamin D supplementation in infancy reduce the risk of pre-eclampsia? The authors in Finland showed that: "We used data on 2969 women born in the Northern Finland Birth Cohort 1966 of whom 68 (2.3%) had pre-eclampsia in their first pregnancy. Risk of pre-eclampsia was halved (OR 0.49, 95% confidence interval (CI) 0.26-0.92) in participants who had received vitamin D supplementation regularly during the first year of life and this association was not affected by adjustment for own birth order, birth weight, gestational age, social class in 1966 and hospitalizations or pregnancy-induced hypertension of their mothers. Together with earlier observations on a reduced risk of type 1 diabetes after vitamin D supplementation, these data suggest that vitamin D intake in infancy may affect long-term programming of the immune response pattern." Pouta A et al. Eur J Clin Nutr. 2007 Sep;61(9):1136-9.
• Prevention of preeclampsia with calcium supplementation and vitamin D3 in an antenatal protocol. Japanese researchers prospectively reduced 37% of pre-eclampsia in high risk cases (as identified by an angiontensin test) with calcium 152-312 mg/day and vitamin D3 supplementation (sorry--didn't understand their dosing 0.5 micrograms per/3 day?) Int J Gynaecol Obstet. 1994 Nov;47(2):115-20.

INCREASED FETAL MORTALITY, PRE-EMIES, SUDDEN INFANT DEATH SYNDROME
Actually little literature exists specifically on this subject (that I could find). SIDS is probably multi-factorial. In utero development of the innervation of the lungs and brain are likely key to susceptilibity factors. I did however find one report which showed low vitamin D levels in all cases of premature and infant death cases.

• Serum 25-hydroxyvitamin D concentrations in sudden infant death syndrome. The lower the vitamin D blood concentrations, the lower the survival rate in these unfortunate babies studied. The author was trying to show no association but if normal 25(OH)D is 60-70 ng/ml then these babies had severe vitamin D deficiency. The levels measured were: "25-OHD was 19.0 +/- 7.9 mg/ml in SIDS, 16.9 +/- 5.2 ng/ml in acute death control infants, and 11.9 +/- 4.4 ng/ml in in-hospital deaths. For four "near miss" infants the mean serum 25-OHD concentration was 21.1 +/- 4.1 ng/ml. The mean serum 25-OHD concentration of 39 living premature or small-for-gestational-age infants at 3 months of age was 26 +/- 9.9. " Haddad JG et al Pediatrics. 1980 Jun;65(6):1137-9.

Perez-Lopez ties it up well for me (Gynecol Endocrinol. 2007 Jan;23(1):13-24)

Vitamin D: the secosteroid hormone and human reproduction

"Vitamin D is a secosteroid with an endocrine mechanism of action which is sequentially synthesized in humans in the skin, liver and kidneys. The active hormone, 1alpha,25-dihydrocholecalciferol [1,25(OH)2D3], is often considered only in terms of its role in controlling calcium and phosphorus homeostasis. However, cumulative evidence points to the presence of vitamin D receptors in many tissues. The present article summarizes key points regarding the participation of vitamin D in pregnancy and breastfeeding. During pregnancy, sufficient vitamin D concentrations are needed not only to address the growing demand for calcium on the part of the fetus, but also to participate in fetal growth, development of the nervous system, lung maturation and fetal immune system function. Hypovitaminosis D has been related to the development of diabetes, pre-eclampsia and fetal neurological disorders. During pregnancy and lactation, calcium from the maternal skeleton is mobilized, with a rise in bone turnover and a reduction in bone mass. It is advisable for pregnant and nursing women to maintain adequate levels of vitamin D, through small doses of solar exposure to facilitate natural formation of the hormone or by ingesting appropriate vitamin supplements."

Next post: More Vitamin D Dosing and Non-toxicity