Lp(a) and Women's Heart Risks

For women with high Lp(a) and high CAC scores, estrogen (including natural, fake and the horsey-hormones) has been shown to in fact be beneficial in controlling CAD risk, events and reduction in Lp(a). Does this translate to men... *ha* I believe it may -- that is why alcohol-extracted soy protein, phytoestrogens and even... BEER help men with Lp(a) and reduce CAD.


With that said, controlling Lp(a) in post-menopausal women has enormous benefits for heart disease. HRT (hormone replacement therapy) is safe, convenient and promotes longevity and optimal heart health. Plus people report better well-being, sharper minds and unrelenting energy. (They say sex is better too.)

Bioidentical HRT and monitoring via salivary/blood testing is the ONLY way to go, according to my personal research.


Uzzi Reiss MD, Michael Colgan PhD, Suzanne Somers, Cheryle Hart MD (hormonesbyhart.com) are all excellent resources.

Each one of the above authors stress an insulin-controlled diet in conjunction with optimizing all 10 hormones (they forgot vit D -- but one of my pts sees Dr. Hart and she normalizes vitamin D [25-hydroxy-D] now).


1. Melatonin

2. DHEA

3. Pregnenolone

4. Estrogen (we have 3 types floating around -- E3 is the best and shown to be cancer protective; avoid E1, higher cancer rates)

5. Progesterone (Dr. John Lee MD obgyn is a good read esp for insulin, promotes avoidance of plastic/pesticides/poisons, etc)

6. Testosterone (yes for women this is very VERY good too -- and reduces Lp(a))

7. Insulin

8. Cortisol

9. Vitamin D

10. Thyroid



Control of Lp(a) is reviewed in great detail in our Part 3 TYP Diet, TYP Lp(a) reports 1 and 2.


Critical components of a successful Lp(a) reduction program at TYP are:

--control of all the above hormones -- ALL TEN

--good adequate sleep (for cortisol reduction and immune system optimization), rest, relaxation, recovery, etc

--exercise -- to reduce belly fat -- including resistance training which grows lean body mass, muscles

--low carb diet -- no wheat or gluten or grains or legumes; minimal fruit

--moderate diversely-colored nonstarchy veggies

--adequate high quality protein (including organic organ meats)

--avoidance of things which set off the immune system -- excessive cardio, excessive endurance training, infections, excessive mental or physical stress, sleep deprivation, etc

--antioxidants: astaxanthin, krill oil, carotenoids, coenzyme Q10, curcumin, alpha-lipoic acid, carnitine, NAC, flavonoids, pycnogenol, mushroom extracts, et cetera -- they are all EXCELLENT

--saturated fatty acids: unrefined coconut oil, MCT oil, fat on grassfed meat/wild game/free range fowl/wild seafood, egg yolks, butter oil (greenpasture.org), (if not casein-sensitive) raw fermented dairy, high-quality 70+% chocolate, organic lard, etc

--ultra high dose EPA DHA fish oil 6-8.5 grams daily (higher quantity, if inflammation is present)

--avoidance of all omega-6 refined veggie oils: sunflower, safflower, peanut, soybean, canola, etc

--intermittent fasting (this replicates the effects of NIACIN combined with all the above strategies)

--niacin 1-2 grams daily

--avoidance of low-fat diets (eg, the AHA low-fat-diabetogenic-kill-ya diet)



If elevated Homocysteine (greater than 8.0) occurs despite all the above strategies, consider adding high doses of B-vitamins
--Folic acid, 1 - 5 mg daily
--Vitamin B12, 1000 mcg daily (adenosyl- and/or methylated cobalamin) sublingual is the best absorbed form
--Vitamin B6, 50 mg daily
--Trimethylglycine (Betaine) 1.5 - 3 mg daily



Sure sounds like... the optimal Paleo warrior diet/lifestyle, right?

And... not unlike a diet/lifestyle of wolves...?

Brain: Sexual Dimorphisms

Striving to optimize all hormones to evolutionarily-normal youthful levels brings about optimal regression/stabilization of any insulin resistance and vascular calcifications. A side effect is optimal lifespan and vitality. These are lessons learned from trial and error, and backed up by meager medical science (albeit exploding in volume). Though we are all a self-experiment of n=1, I find it astounding that we are more bound by our experiences by our vast similarities than by our vast differences.
--Vitamin D (Calcidiol [25(OH)D] blood levels: 60 - 70 ng/ml)
--HDL-cholesterol (Yes... I believe it is a hormone; HDL-receptor=SR-BI. Large HDL has powerful anti-inflammatory, anti-cancer, anti-atherogenic, pleiotropic anti-aging effects. Goal HDL: Concentration greater 60 mg/dl with Large-HDL outsizing and outnumbering Small-HDL by greater than 60% of the total (because HDL2 tracks with longevity). Goal HDL: Avg particle size greater than 9.2 nm on NMR/VAP)
--Insulin (less than 5 mIU)
--Cortisol (stress hormone: low end of normal)
--PTH (parathyroid hormone: lower end of normal)
--Free T4 (active thyroid hormone: upper end of normal)
--TSH (thyroid stimulating hormone: ~ 1.0 mIU)
--Free Estrogen (E2, E3: normal)
--Progesterone (P: normal)
--Free Testosterone (T: normal)
--DHEA-S (normal)
--Omega-6/Omega-3 (Fatty acid profile test: 1.5 to 1.0 ratio (similar to traditional Okinawan and Inuit))
--(Adiponectin, Leptin, Human Growth Hormone, IGF-1, Pregnenolone, Myostatin, Melatonin, Eicosanoids, Retinoids, Essential/nonessential Fatty acids, Saturated Fatty Acids, Essential/nonessential Amino acids (eg Arginine, Taurine), Neuropeptides (eg Tyr-Arg=kyotorphin), etc)



Why are hormones so important? I've wondered this frequently lately after being diagnosed with Vitamin D deficiency. Not only are hormones (and pro-hormones like vitamin D) a focus of many disease reversal protocols (i.e. cancer, infertility, etc), but they define who we are... what we are... what gender... social interactions... moods... libido... bone health... inflammatory status...


Our hormones and/or lack of hormones makes us do a lot of things... Sometimes unconscious thoughtless things... A recent study in oral contraception-users demonstrated how hormone-manipulation lead to different mate selection. Millions of women use hormonal contraception to prevent ovluation, control acne or reduce painful PMS/peri-menopausal/fibroid conditions.
The pill makes women sniff out wrong partner
Effect of Putative Male Pheromones on Female Ratings of Male Attractiveness: Influence of Oral Contraceptives and the Menstrual Cycle


Can these be creating a generation of children with less hardy genetic stock? Does how we perceive sexual characteristics and dimorphisms (like a deep baritone voice, sexy/symmetrical body) affect our future progeny?

Evolution-wise it does indeed make sense that 'opposites attract.'


Let's geek out. Science-wise, this could be translated into 'dichotomous Major Histocompatibility Complexes captivate.'

Our body odor in fact may indicate our MHC's which are genes that encode our immunity. MHCs help determine matches between organ donors and organ receivers. Pheromones are emitted from glands and detectable in body odor. How do we sense pheromones?
Body odour preferences in men and women: do they aim for specific MHC combinations or simply heterozygosity?
MHC-dependent mate preferences in humans.
Human body odour, symmetry and attractiveness.


Through our noses which are connected to our reptilian/fish-brain which control unconscious, visceral functions (cardiac, vascular, GI, pulmonary, reproductive), and other roles vital for self-preservation like focus/flight/fright/fight/fertilization/repetition. Dr. Perricone the tan, attractive dermatologist who knows his hormones discusses the benefits of pheromones in reducing cortisol and adrenaline and the effects on mood and mate selection HERE. PBS television endlessly showcase his lectures during pledge drives. I wonder why? He does offer good science (and he's certainly easier on the eyes vs. Weil or Orman) and good entertainment. His line offered a $200 pheromone product previously, but apparently it has been scaled down to a smaller, less expensive solution (probably more suited to the recession... but uuummmm I wouldn't really know). Does having optimal pheromones make you look younger, more radiant, less wrinkly?? More irresistible to the opposite sex?? Does having optimal hormones build better houses, hunt for bigger bison, fish for copious catches? Does having optimal hormones make you smarter? More alert? More strong? Does having optimal hormones guarantee getting laid??!? I sure hope so...*wink* Being a more attractive and 'appealing' mate sort of guarantees continuation of ancestral genes. Would you want to mate a potato? Attraction to opposite immune MHC's guarantees diverse traits which can increase more optimal gene-environment interactions. Makes immense sense to me. In my little n=1 experiment I started on a topical hGH (human growth hormone) product similar to one offered at Bloomingdale's for the skin. After 1-2wks, I noticed that the skin looked fantastically better. Personally I'm convinced that youthful hormones -- even topical ones -- bring about youthful results. With oral Vitamin D for one year, I have already experienced more youth, ageless abundance of hair/nails/skin, lean muscle gains/speed, imperviousness to infections, and breathing easier (no more asthma). Drowning in your own lung secretions is slightly non-conducive to survival.


One fish species in Central America known as the wrasse (see picture) in fact changes genders via hormone changes. When the male leader becomes absent or a pre-ponderance of female wrasses occurs, a female wrasse will undergo a 'sex change' and transform into a secondary male wrasse.

Male sex organs transform into female structures.

I find that a-s-t-o-n-i-s-h-i-n-g.

We don't need exogenous stem cells. Does all life on earth contain an inherent ability to transform when giving the appropriate hormonal cues and environmental triggers? I witness transformations everyday...from my own practice, co-workers and friends' stories, on the cardiology forums and my Crossfit gym/network. Men with 'man-boobs' (who I envy if they're cup-D or higher *wink*) become male-gendered again. Women with testosterone/estrogen (xenobiotic) excess and progesterone deficiency resume feminine secondary traits. An interesting story that Nicki and Robb Wolf told at a nutrition certification at their Crossfit gym in Chico was how they were going to add a disclaimer on their waiver: Paleo nutrition and Crossfit can cause pregnancy; do Crossfit at your own risk! They reported 11-12 pregnancies ALL in the same month among women who stated they couldn't become pregnant for years...!! I wonder why?? (stopping canola/Mazola/toxic-omega-6s + those 'd*mn dirty grains'; eating fats, fish oil, seafood/grassfed, vegs, nuts/seeds, and adding functional movement with intensity)
Sex Change in the Bluehead Wrasse: Temporal Concordance of Changes in Brain and Behavior (See the Table: great review of neuropeptides Arg-vasotocin v. Arg-vasopressin in mammals and brain, behavior, and subsequent sexual dimorphisms)
Surroundings cause tropical fish to change sex: scientists
Crowds cause sex change



Our middle brain is known as the limbic system (PALEOpallium) which is believed to be derived from early mammals. The limbic system controls ludic behavior (not lewd, l-u-d-i-c, from Latin 'to play'). It is also associated with passion, happiness, fear, love, joy. Have you noticed on Planet Earth that only the mammals play? Birds and bees do not. Neither do reptiles. The genetic advantage of 'playing' maybe connecting learning experiences from the past to the present. Can the promotion of curiosity, exploratory thoughts, and artful/inquisitive natures be a survival benefit? A shore-based diet rich in mollusks, seafood and fish is believed to be the turning point for human dominance of the earth and the food chain (yes, it can be argued otherwise, probably depends on the continent? I dunno). Mollusks and seafood are abundant sources of omega-3 long-chain fats known as EPA and DHA. Land mammals also contain EPA and DHA in organ meats and grassfed dairy/muscle meat/adipose. Omega-3 fats EPA and DHA have been shown in infants to raise IQ points and at high dose, improve signs and symptoms of depression and schizophrenia.

DHA deficits of the third brain, the neocortex/neopallium, are severely correlated to brain disorders like bipolar and schizophrenia. R.C. Caspar, a Stanford researcher, wrote "Human neurodevelopment is the result of genetic and environmental interactions. This paper examines the role of prenatal nutrition relative to psychiatric disorders and explores the relationship among nutrients, mood changes, and mood disorders. Epidemiologic studies have found that adults who were born with a normal, yet low birth weight have an increased susceptibility to diseases such as coronary heart disease, diabetes, and stroke in adulthood. (Nutrients, neurodevelopment, and mood. Curr Psychiatry Rep. 2004 Dec;6(6):425-9.)" He discusses beneficial placebo-controlled research results of EPA and DHA on depression and bipolar.
Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients.
Attention deficit disorders--drugs or nutrition?
A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids.
Role of omega-3 fatty acids in brain development and function: potential implications for the pathogenesis and prevention of psychopathology.
The role of omega-3 fatty acids in mood disorders.



Paleo exercise has a component of 'playfulness' and random spontaneity. At Crossfit, we hardly repeat the same routine. In fact, at with paleo and Crossfit, omega-3 fish oils are highly-suggested. EPA and DHA fish oils can affect physical results, performance and notable gains, as well as cardiovascular disease reversal. Omega-3 oils can allow us to play harder and longer. With stronger hearts and muscles. With great endurance. Without electrical conductance disturbances (like atrial fibrillation).
Omega–3 Fatty Acids, Exercise, Physical Activity and Athletics
Fish oil reduces heart rate and oxygen consumption during exercise.
Intakes of long-chain n-3 polyunsaturated fatty acids and fish in relation to measurements of subclinical atherosclerosis.
Effect of Erabu sea snake (Laticauda semifasciata *SNAKE OIL he hee*) lipids on the swimming endurance of aged mice.


Strength manifests in a variety of avenues. For survival, it appears to me that mental vigor, intelligence, genetic disposition, and physical power are all indispensable. Is it unusual that a convergence between the best things for our brain/sexual-dimorphisms, our also the best for our body and heart. Maybe not! Finally a 19-year study in the BMJ by Dr. S. Blair demonstrates that superior muscle strength relates to lower mortality from heart disease, cancer, and all cause-death in men, even after adjusting for cardiovascular fitness (on treadmill testing). Full PDF click here. I first came across this landmark trial in my fave mag FitnessRx for Men Jan 2009 issue, p. 142-144. I love this journal... for the ummmmm... in-depth... uummm scientific articles.
Association between muscular strength and mortality in men: prospective cohort study.

As the author Fahey EdD concluded in his review...'Get STRONG and live long.'


Don't be sarcopenic.

Greek: Poverty of the Flesh

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

Waning Estrogen and HDL3b

In Krauss and Williams et al research on lipoproteins in Bay Area Mormon kindreds, they talked about my favorite things (other than the sound of music)... on their relationship with HDL2b, the regression lipoprotein subfraction which performs in the vasculature like liquid D-R-A-N-O:
--young age
--low BMI/fat body composition
--more alcohol (for women only -- j/k --the stats didn't reach significance)
--estrogen (for getting our both mojo-jo-jo and HDL2b on) -- both natural and substituted

Estrogen has great affects on improving HDL2b from birth to menopause for women (and men too?). And after menopause, women have a pattern of elevated HDL3c/3b like men (not pretty -- the blip above for 3b is even greater than the 3b blip for men Fig 1 below). Not shown in the data or graphs, the authors note that for the subjects taking estrogen replacement did display greater levels of the larger-sized HDL3a and HDL2a. No mention of HDL2b which was odd since estradiol has been shown to increase HDL2b quite significantly in menopausal women. The authors also didn't report the specific type of estrogen estradiol (better) v. Premarin (bad).

I found this article so neat on many levels -- the authors really focused on subfractions of a previously under-appreciated lipoprotein ignored by statinators, the HDLs 'happy' good cholesterol. They are not from a major medical academic institution (LBL does not have that distinction around here). And lastly they used technology that we love at TYP to 'track' health/health status.


-BG

HDL2b -- Age, Adiposity, Alcohol and Estrogen

The lipoprotein subfraction HDL2b is emerging as the marker for regression of plaque and longevity. Even evidence from 10-15 yrs ago revealed this remarkable relationship. Looking to centenarians, scientists often search for answers and clues to longevity and control of chronic illnesses. These Italian researchers examined the the relationship between 2 subfractions of HDL -- small dense HDL 3a and large fluffy HDL 2b. The HDL 2b subfraction appear protective (at 32.4%) compared to younger/healthy matched controls (at 23.4%) and HDL 3a, appear degenerating for longevity. The interesting thing to note is that total HDLs were similar between all groups. In other words, the HDL from traditional labs tells nothing about HDL2 or HDL2b or HDL 3a. (Here Dr. Davis rails about the failures and weaknesses of conventionalist-type medicine in their overreliance on Friedewald's equation. )

"In order to assess the role of HDL on longevity, we studied HDL subfraction distribution in centenarian women compared with a group of weight- and gender-matched healthy normolipidemic controls. We did not find any significant difference in the mean plasma lipid, apolipoprotein, and Lp(a) levels. On the contrary, in spite of similar HDL-cholesterol concentrations (1.32 +/- 0.41 mmol/l in centenarians vs. 1.32 +/- 0.25 mmol/l in controls, p = not significant), HDL2b and HDL3a levels were, respectively, significantly increased and significantly reduced in centenarians in comparison with controls (HDL2b 32.4 +/- 9.2% in centenarians vs. 23.4 +/- 7.7% in controls, p less than 0.002) and HDL3a 26.3 +/- 9.8% in centenarians vs. 34.1 +/- 7.3% in controls, p less than 0.01). HDL2b levels were significantly raised and HDL3a levels were significantly reduced in centenarians in comparison with both 'middle-aged' and 'elderly' subjects, whereas no difference for any HDL subfraction was found between the two groups of controls of different ages."

• Barbagallo CM, Averna MR, Fradà G, Noto D, Cavera G, Notarbartolo A.
  Lipoprotein profile and high-density lipoproteins: subfractions distribution in centenarians. Gerontology. 1998;44(2):106-10.
  PMID: 9523222

HDL Subclasses

The subclasses of total HDL are defined via absorbency of a protein stain which serves as an index of mass concentrations at intervals of 0.01 nm. We desire a reduction in CETP activity to prevent transfer of mass from HDL to VLDL (small dense LDL).

• HDL3c (7.2 to 7.8 nm) -- plaque-builder (bad)
• HDL3b (7.8 to 8.2nm)
• HDL3a 8.2 to 8.8 nm)
• HDL2a (8.8 to 9.7 nm)
• HDL2b (9.7 to 12 nm) -- plaque-BUSTER (good)

Research that came out of the Lawrence Berkeley Labs in 1993 also reinforced how reductions of HDL2b parallels how known risks for CAD go up with age, adiposity and lack of estrogen. Williams et al studied HDL subfractions in Mormon men and women here in the Bay Area. Some Mormons kindreds did drink and smoke -- *HOLY MOLY BATMAN* don't tell the church of LDS -- and their data were excluded from relevant analyses). The alcohol factor is curious -- for women it may appear protective however for men no distinct protective benefit for HDL2b appears strong because a corollary increase in HDL3b and 3c occurs with alcohol consumption (??did that potentially negate the mild protective 2b increase?).

• Williams PT, Vranizan KM, Austin MA, Krauss RM.
  Associations of age, adiposity, alcohol intake, menstrual status, and estrogen therapy with high-density lipoprotein subclasses.
  Arterioscler Thromb. 1993 Nov;13(11):1654-61.
  PMID: 8218107

Here are their conclusions as they summarized:

• HDL3b concentrations were higher after menopause than before
• Eighty-eight percent of the increase in HDL associated with estrogen replacement (conjugated/horse hormones most likely) in postmenopausal women occurred within HDL3a (bad) and HDL2a.
• Adult men (> or = 18 years old) had significantly higher HDL3c and HDL3b
• Adult men had significantly lower HDL2b and HDL2a levels than younger boys (why?)
• There were no significant differences between the HDL profiles of women and younger boys, suggesting that divergence in HDL occurs during puberty
• Compared with the women, adult men had higher levels of HDL3c and HDL3b
• Adult men had lower levels of HDL2b, HDL2a, and larger-diameter HDL3a particles compared with women (is this why women live longer then men??? )
• In both men and premenopausal adult women, increasing levels of body mass index were associated with higher levels of HDL3b (bad) and lower levels of HDL2b (very very bad).
  

The authors noticed that "Reported alcohol intake in adult men correlated with two HDL regions: one within the HDL2b region (good) and a second within the HDL3a/2a region (bad), whereas in women the positive correlation between alcohol and HDL levels was within the HDL2b region only."












So what are the most potent things we can do to raise HDL2? We know that most of the HDL2 increases are due to HDL2b increases. HDL2 in fact is a good surrogate for the regression marker HDL2b. Studies show this -- and the TYP program reinforces this:

--Achieving normal BMI. Reducing adiposity (esp central though the above study does note that central vs. peripheral was not measured) will raise HDL2b and lower HDL3a/HDL3b/HDL3c

--Reduce your 'biological age' -- how? movement movement movement, vitamin D3, etc

--Take Niacin -- this B3-vitamin which mimics fasting and ketosis raises HDL2 100% (or occasionally get ketotic with intermittent fasting -- when you're not stressed/sleep deprived which is when Cortisol is excessively high) in trials

--Take Fish Oil -- at 'low dose' 4 g DHA per day HDL2 increases of 30% are observed (is more better? yes)

--Restrict carbohydrates (yes sirree, that includes F - R - U - I - T - S , ie, Nature's candy) and again the same researchers at Lawrence Berkeley Labs Williams, Krauss et al confirm this here. And even for you elite athletes out there -- the low HDL corresponds to CAD risk -- and carb (yes fruit) will trigger concomitant huge magnitudes of insulin eruptions and reductions in HDL2b and increases in VLDL/small LDL. The research demonstrated that here well.

--Consume a higher fat and saturated fat intake...like lauric acid (unprocessed coconut oil), caproic/caprylic and butyric acid (raw pasture raised butter oil)

--Get on Bio-idential/tx estrogen which raises HDL2b 150% (see below) (if you're lacking -- yes even men? perhaps... Post-menopausal women do apply Testosterone cream, why not vice versa?) In the study below Ethinyl Estradiol 0.1mg orally was taken by pre-menopausal women and resulted in total HDL increasing 38.3% and HDL apoA1, 25-27%. Oral estrogen sometimes worsens cholesterol for some -- transderm/topically applied are preferable for some. Are women the superior species?

Well... though what would we be without the men we stand behind?

• The effects of estrogen administration on plasma lipoprotein metabolism in premenopausal females. Schaefer EJ, et al. J Clin Endocrinol Metab. 1983 Aug;57(2):262-7.
  PMID: 6408108

--BG


P.S.
If you want plaque and a reduction in heart-protective HDL2b, follow the AHA Step I low-fat diet. The researchers are GENUISES... they repeated the same results in obese, postmenopausal women (but at least their conclusions were rationale this time).
Effects of an American Heart Association step I diet and weight loss on lipoprotein lipid levels in obese men with silent myocardial ischemia and reduced high-density lipoprotein cholesterol.Katzel LI, Coon PJ, Dengel J, Goldberg AP. Metabolism. 1995 Mar;44(3):307-14.

ENJOY! And...give a copy to your conventionalist MD... you have my permission...no need to wait for April Fool's Day or another heart attack...