Vitamin K2: Building bones while beating back arterial calcification

Vitamin K2's time to shine has come—move over vitamin D! Once only known for its role as a "koagulation" factor in blood clotting, vitamin K2 is emerging as another fundamental anti-aging nutrient. While vitamins D and E have garnered the majority of interest in the last decade, the impact of vitamin K2 on aging bones and hearts demands that we give it equal attention.
Whereas most vitamin and mineral supplements use vitamin K in its form of K1 (phylloquinone sourced from plants) because it is easily available and cheap, it is the natural form of K2 (menaquinone sourced from friendly bacteria) that is the most biologically active and shown to enhance both bone formation and vascular health.

The full compilation of recent research underscores the idea that K1 and K2 should be appreciated as separate nutrients with distinct physiological actions and benefits. K1 is the more familiar vitamin known for its key role in directing blood-clotting in the body and the one given as a shot at birth (a common practice in many countries to curtail hemorrhage incidents in newborns.) The picture for K2 seems to be a bit more varied and is key in regulating calcium balance.

Vitamin K2 acts by activating the bone-building hormone (carboxylating osteocalcin) to clear calcium from the arteries and use it in bone mineralization. It effectively removes calcium that would otherwise end up deposited in arterial plaques. Since protecting arteries and soft tissues from calcification is one of the most important ways to stave off the ravages of aging on the body, consuming enough vitamin K2 daily is key for a long, healthy life.

Getting Enough K2

Because vitamin K2 is synthesized by friendly bacteria in the intestine, nutrition scientists have long assumed that that deficiencies were rare. However, new data are showing that intestinally synthesized vitamin K is not absorbed as easily as previously thought. Vitamin K also preferentially accumulates in the liver where it does have a clotting factor role.

In fact, once overlooked because "time to clot" was the test for vitamin K status, it is here where we are now seeing new signs of vitamin K deficiency previously only seen with vitamin D deficiency—fragile, brittle bones and increased fractures—even with adequate calcium and vitamin D.

Most people in North America should increase amounts consumed daily. The evidence finds that only with much higher intake do bone cells get their share and the same holds true for removal of calcium in arteries.

People can obtain enough vitamin K2 by eating plenty of fermented foods such as cheese, sauerkraut, and natto (a traditional Japanese soy-based food). Supplementation is another viable option as achieved with a quality multivitamin.

Regardless of how one gets it, it’s important not to underestimate value of this underdiscussed nutrient and to understand that most people are not getting enough. Consuming sufficient amounts of K2 along with a healthy diet will increase odds of a healthier life with clear arteries and stronger bones.

Sources

McCann and Ames. Vitamin K, an example of triage theory: is micronutrients inadequacy linked to diseases of aging?. Am J Clin Nutr 90:889-907, 2009.
Vitamin K2. Monograph. Alternative Medicine Review 14(3):284-293, 2009.
Koitaya. Et al. Effect of low dose vitamin K2 (MK-4) supplementation on bioindices in postmenopausal Japanese women. J Nutr Sci Vitaminol. 55:15-21, 2009.
Gast, et al. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovas Dis 19:504-510, 2009.
Shea, et al. Vitamin K supplementation and progression of coronary artery calcium in older men and women. Am J Clin Nutr 89: 1799-1807, 2009.
Shea MK, Booth SL Update on the role of vitamin K in skeletal health. Nutr Rev 66(10):549-57, 2008.

Slightly adapted from my original post here.
READ MORE - Vitamin K2: Building bones while beating back arterial calcification

Is there a link between telomeres and dietary fiber?

New evidence published in Archives of Internal Medicine has it that eating more dietary fiber, particularly from whole grains, could lead to a longer life. The large study found a high-fiber diet reduced risk of heart disease and cancer, as well as infectious and respiratory illnesses.

This is great news for those eating diets high in fiber. What’s also interesting is that another reason why dietary fiber is protective to health is because of its influence on telomeres. Telomeres are the protective caps at the end of chromosomes, and their length is considered the closest way to measure lifespan in humans.

As reported in a prospective cohort study published in the March 2010 issue of American Journal of Clinical Nutrition (AJCN), telomere length is positively associated with higher fiber intake in women. Dietary fiber from whole grains appears to provide the strongest benefit.

In addition, in the AJCN study, the researchers found telomere length was negatively associated with increased waist circumference and higher intake of omega-6 fatty acids in the diet.

Because the study was only observational, the authors reported that further investigation is necessary to further illuminate the link between dietary fiber and telomere length.

Whole grains examples are rolled oats, buckwheat, whole wheat, and wild rice. The grains contain the entire grain kernel, which include the bran, germ and endosperm. Less than 5 percent of Americans consume the minimum recommended amount of whole grains, which is about 3 ounce-equivalents per day, according to U.S. Department of Agriculture.

Americans barely receive half the amounts of dietary fiber recommended daily. How much dietary fiber is enough? The recommended amounts are 25 grams of fiber for women and 38 grams of fiber for men.
The AJCN study was among the first to document the relationship between diet and telomere length. The authors of the study concluded that the results provided more support that an improved diet and lifestyle would indeed help to slow the aging process.

"Telomere shortening is accelerated by oxidative stress and inflammation, and diet affects both of these processes," the authors report.

Studies have also found that the following changes in diet and lifestyle are all positively associated with telomere length:
  •  not smoking
  • exercising regularly
  • maintaining a normal body weight
  • healthy management of stress
  • consuming sufficient long-chain omega-3 fatty acids from fish weekly
  • maintaining a healthy vitamin D status
  • consuming a quality multivitamin daily
  • consuming antioxidants such as CoQ10 and green tea
Sources:

Park Y, Subar AF, Hollenbeck A, Schatzkin A. Dietary Fiber Intake and Mortality in the NIH-AARP Diet and Health Study. Arch Intern Med 2011.
Cassidy A, De V, I, Liu Y et al. Associations between diet, lifestyle factors, and telomere length in women. Am J Clin Nutr 2010;91:1273-80.

Post originally written to be posted here.
READ MORE - Is there a link between telomeres and dietary fiber?

Pornography in the Primordial Soup

Panel of scientists debate on "What is Life?"

Sometime between 4 and 3.5 billion years ago, the emergence of life had intense beginnings on a young planet in the midst of a so-called primordial soup—consisting of water vapor, carbon monoxide, carbon dioxide, nitrogen, and ammonia and shaped by strong winds, electrical storms, volcanic eruptions, and ultraviolet radiation.

In 1953, Stanley Miller and Harold Urey put Earth's primitive conditions to test for the first time in a famous laboratory experiment. It yielded variety of amino acids and organic compounds. The researchers realized something more: that no early form of life could have ever survived the world of today, because of the presence of oxygen that directly attacks at the bonds that holds together complex molecules.

Scientists also now know that the original blueprint of life was not DNA, but short RNA strands that may have also served as their own biological catalysts, before enzymes ever evolved, providing for self-replication. This early RNA world would eventually give rise to DNA, which used RNA as its template for encoding the genetic information to build proteins.

Still, there are several other questions that remain surrounding life's origins such as How can life be defined? Where did it happen? What came first: replication or metabolism? Could life have happened elsewhere in the universe? What would an alternative form of life and biochemistry look like?

Last weekend, to discuss the questions, a small panel of six scientists gathered at workshop at Arizona State University with a major goal of charting out the steps between the RNA world and greater complexity. Some would say theirs was a hopeless cause and a waste of time.

Then, on Saturday, February 12, a public debate  took place between them with an overarching theme entitled, "What is Life?" Theoretical physicist and cosmologist Lawrence Krauss, ASU professor and director of ASU's Origins Project defended the exercise as uniquely human.

"It's a profound and deep question that hits at everything we think about," Krauss said, noting how the question has a powerful draw. "It sounds like a simple question, the answer isn't so simple. In fact, every time I think about that question, I think about pornography."

He referred to a 1964 Supreme Court case where Justice Potter Stewart once was asked to explain the definition obscene pornography. "I know it when I see it," the judge responded. Krauss said, "In some sense, life is like that."  

Life: Complexity with a Specified Direction

Evolutionary biologist Richard Dawkins further  elucidated the significance of the question in characteristic eloquence, "This may be the only planet in the universe that contains eyes to see it, brains to think about it, and wonder about it. I don't believe that. I suspect there is plenty of life in the universe, but this is the only kind of life we know about."

According to Dawkins, because the laws of physics apply all over the universe, it is likely that life could have materialized many times by the process of evolution by natural selection. Life, then, would have to be defined as anything that is highly statistically improbable, but that appears to have a specified direction.

"You have to add that 'specified direction' because with hindsight you could say any old heap of rubbish is statistically improbable in that there has never been a heap of rubbish exactly the same," Dawkins said. "What's special about life is that living things are statistically improbable in a direction, which you could have specified in advance. It's not always exactly the same, but birds are good at flying, fish are good at swimming, moles are good at digging. All living thins are good at something, whereas lumps of rock aren't.    

Whatever life is, it is characterized by its complex molecules that must somehow create the energy to convert raw material into a structure, all while excluding anything that may be toxic to those reactions of metabolism and reproduction. This is why geneticist and Nobel Laureate Lee Hartwell argued, "Inevitably, life will be cellular. Cells will have been selected to have an optimum size and optimum structure for whatever lifestyle they happen to have."

Searching for a Second Genesis

A sort of definition of what to look for was heartening for NASA planetary scientist Chris McKay, "What Lee said was a beautiful synthesis of how we can search for life, and I want to take that to the specifics of how do we do it in near tem missions in our solar system."

There is an advantage to finding other forms of life in our own solar system, argued McKay, because "then we'd know that life is common in the universe." The task of finding other forms of life in the solar system, even on our own planet, is one promoted by cosmologist and astrobiologist Paul Davies.

Davies doesn't see things quite the same way as McKay. "How can we find this second sample of life? Chris has said one way you can do that is you can go somewhere else in the solar system and find it there. That's great. But it's also very expensive. Is there another way? Well, no planet is more Earth-like than Earth itself. Shouldn't it have occurred many times right here on our home planet? How do we know it didn't?"

While Davies looks for alternative life on Earth—a process that he boldly claims can be completed in less than a decade—biologist and entrepreneur Craig Venter is more interested in creating synthetic life.

Venter explained how he and his colleagues synthesized DNA and chromosomes and inject it into E. coli, which he likened to creating a computer program that builds its own computer, or as he puts it, "A situation where the software actually leads to building its own hardware, but we're trying to go much further. We had to learn how to boot up this bacterial genome."

Change the DNA, change the software, and you change the species, Venter explained, and as others have pointed out, his team did use a living cell, but the cell was the first one to ever have synthetic DNA.

Living Artificial Intelligence

Among these scientists, one thing was certain: the definition of life could not be agreed upon in the face of alternative forms of life in the universe, in our own solar system, on the Earth, or from creating life from scratch. But, perhaps, a definition of life isn't needed after all because, as Krauss put it, anyway, it could change.

"Let me throw it in a completely different direction," Krauss offered in the debate."When computers become conscious, which they will—my Mac is far closer than the PC—will we call them life? And they'll object if we don't, I suspect. I think the definition is a moving target."

After all, the difference from what Venter is accomplishing—with software that makes its own hardware—and computers is that computers simply haven't done that yet (made their own hardware), but when they do, which will happen in at least one or two decades, Krauss said, "they will become the dominant forms of intelligent life on the planet and biology will have to incorporate that in order to keep up."

At the end of the debate, the inevitability of life in the universe was the lesson really learned, given that there could be life lurking almost anywhere.

Be it in a biological world, a  synthetic world, or another kind, life can defined as simply… we'll just know it when we see it. 

To read more about the entire weekend conference on origins of life, see Dennis Overbye's article in the New York Times.
READ MORE - Pornography in the Primordial Soup

Evolution of Lactose Tolerance in Africa

Sarah Tishkoff
Most African populations have lactose intolerance, but as recently as 3 kya a few pastoral populations have gained the ability to digest milk, which provides evidence of yet another example of ongoing evolution in human population since the time of their origins.

Sarah Tishkoff has been studying this phenomenon of recent lactose tolerance in African pastoralist populations. She shared her findings on Sunday morning at #AAASmtg in Washington DC.

The ability to digest milk as infants is with the expression of lactase-phlorizine hydrolase (lactase), which is specifically expressed by brushborder cells in the small intestine.

But shortly after weaning, the expression of lactase decreases sharply -- that is, except in populations that are lactase persistence. In 2002, an elegant genetic study found the gene for lactase in European populations.

Tishkoff showed us in charts and on a map how she performed genetic studies on the African pastoralist populations with lactase tolerance. Based on the findings, she found a perfect example of convergent evolution -- that several of the populations had developed lactose tolerance in different ways genetically -- because of strong selective pressures to drink milk.

With her latest study and archeological data, she is now tracking the origins of pastoralism. She showed us a map (Smith 1992) where it's clear that most lactose tolerance emerged only in the last few thousand years, but at different times. Her research confirms that pastoralism was brought into southern Africa only recently, most likely from the Great Lakes region.

"So, are humans still evolving? Yes," Tishkoff said.

Why was milk selective pressure so strong? There has been a lot of debate, Tishkoff said, such as whether it is the source of water, protein, or calcium. But it's not everywhere, so there has to have been a cultural transformation in each region.

"There's only some environments that can handle that cultural development," Tishkoff said, but in each case, there has to be an underlying genetic variation and the different variants suggest that perhaps for some populations had a more difficult time with the change or took longer to adapt to it than others.
READ MORE - Evolution of Lactose Tolerance in Africa

The Nature of Human Skin Pigmentation

Nina Jablonsky
On Sunday morning at #AAASmtg in Washington DC, Nina Jablonsky talked to use about human skin pigmentation as an example of natural selection.

"Human skin is colorful, it's mostly naked, it's sweaty, and it's tough yet sensitive," Jablonsky said. The gradient of human skin pigmentation is very clear in the old world, as it's lighter in the northern countries and darker in Africa.

But why did human skin pigmentation evolve as it did? When you look at other apes and humans, our relatives have lightly pigmented skin covered by dark hair -- this was the ancestral pigmentation of our lineage.

"When you think of Lucy's species, you can think of lightly pigmented skin covered by dark hair," she said, noting that eventually as the hominins became more naked they developed more melanin.

When Homo ergaster 1.6 mya was foraging in the savannah, the species would have needed more naked and sweaty skin for keeping cool. In addition, Jablonsky's research has found that permanent dark pigmentation evolved 1.2 mya, at the same time as these other developments -- an interesting development!.

Exposed skin could lead to disease states, so by increasing the amount of pigmentation, H. ergaster protected the species and the pigmentation was selected on.

Ultraviolet radiation (UVR) had a lot to do with the advent of darker skin pigmentation. On a map (by George Chaplin based on NASA TOMS7 satellite data) of annual average UVR, Jablonsky was able to clearly show the strength of UVR

"We evolved initially in equatorial Africa and then we had two waves of dispersal from Africa," Jablonsky said. "This really changed the selective genes for human skin fundamentally."

The key thing about ultraviolet radiation is that wavelengths do different things to the human body. In general, UVR does a lot of damage, such as DNA damage leading to skin cancer.

Skin cancer generally affects people as they're older beyond their reproductive years. However, the sun has a definitive effect on folate metabolism. One of the key things we see as important, is the effect on folate metabolism on birth defects. Because folate is needed for making DNA and the competition for folate is intense in the presence of UVR,  "why not increase the amount of melanin -- a superb natural sunscreen -- the evolution of permanent melanin was extremely important in high equatorial radiation levels."

However, melanin comes with a downside. It slows production of vitamin D precursor in the skin, which is essential for calcium metabolism and bone health, as well as incredibly important to the maintenance of a strong immune system.

If we look at our hairy timeline, 6 mya we had hair and light skin, then with dispersal from Africa into India and Asia, then eventually Indonesia and Europe, what did UVR have as an influence?

To Jablonsky, it is the combination of needing to protect against DNA damage and folate metabolism as much as possible, but while naturally selecting for less skin pigmentation for keeping the skin light enough to absorb enough UVB rays to create vitamin D.

Indeed, we have an independent evolution of depigmentation of humans in Asia and in Europe. And we also know that the Neanderthals experienced the same selection of depigmentation. There are many genes involved in pigmentation and Jablonsky said she has even found in some populations, where the amount of UVR changes by season, that people have adapted to change the amount of melanin in their skin throughout the season

Nowadays, accelerated rates of movement around the world, has put humans in environments that are poorly matched, Jablonsky said, which has created serious health problems such as with rickets in children, birth defects, and even metabolic syndrome.

For the purposes of education on health, we need to teach that skin color is an adaptation. It is the most visible product of evolution by natural selection on the human body. This is why we need to use it to teach evolution, Jablonsky said.

Additional note posted Tuesday, Feb 22. I discovered afterward that Jablonski has a wonderful TED talk that I think everyone should watch, so I posted it below.

READ MORE - The Nature of Human Skin Pigmentation

Designing biology

Frances Arnold
Where can we find a cure for cancer, new semiconductor technology, or the solution for turning waste plant materials into biofuels? The answer is enzymes that are produced through "directed evolution," according to Frances H. Arnold, professor of chemical engineering and biochemistry at the California Institute of Technology.

Arnold's lab doesn't synthesize enzymes as other labs do. She and her team "evolve them" toward a certain desired goal in the same way that nature has done it for 3.5 billion years.

Aronold presented an overview of her budding field of work to an audience at American Association for the Advancement of Science annual meeting (#AAASmtg) in Washington DC. The field of directed evolution is relatively new and includes few people at the present time, but Arnold sees high hopes for the future.

"When I started engineering proteins a long time ago, there appeared to me an algorithm that dos a really good job and that's evolution," she said. "Evolution works because the regions that life has discovered and explored are rich in function. Directed evolution exploits smooth paths in the fitness landscape."

The fact is, DNA is cheap and easy. Designing it isn't.

"We're getting really good at making DNA. The price is dropping every day," Arnold said. "But we don't know what to write. We can synthesize any sequence. We can insert new code (referring to Craig Venter's recent success), but we don't know how to write it. We don't even know how to write a single protein."

And, when it comes to enzymes for use inside a complex biological system, she says,"Details matter. We don't understand the details."

Freed from constraints of worrying about biological function, directed enzyme evolution allows Arnold's team to explore new pathways and possibilities.

Arnold presented a few of her enzymes that have been created through directed evolution. Her source materials are from every possible place -- the "heel of your shoe," for example -- and she doesn't limit herself to what's available.

By combining several different enzymes and selecting for specific active sites, she can produce more stable proteins that perform practical work.

Where is directed enzyme evolution going in the future? Arnold says that functional protein can be used in several ways. One example Arnold gives is in materials chemistry, such as the work of Angela Belcher of MIT, who uses virus proteins to enrobe minerals onto protein coats.

"You can make a virus that really loves to bind to a single-walled carbon nanogen," Arnold said, which would be a boon for semiconductor technology.

There is really no end to the influence that directed enzyme evolution could have on the world, from highly specific targeting in biological systems to technology.

In short, there's no doubt of an exciting future in intelligently designing new biology.
READ MORE - Designing biology

How environmental change shaped human evolution

Anna Di Rienzo
Humans originated in Africa and then dispersed all over the world to environments that differ in terms of climate, biodiversity, etc, which has brought selective pressures on different populations. At #AAASmtg in Washington DC on Saturday, Anna Di Rienzo presented her research on the how this dispersal has left signatures of adaptation to the pressures. Here are my notes from the talk.

The "Out of Africa" theory has it that humans left Africa 50 Kya and then Neolithic revolution happened 14 Kya. They shifted away from foraging subsistence to horticulture. We also know that levels of human skin pigmentation changed with latitude of populations. In addition, body size and proportions changed. For example, Inuit have quite different proportions for the cold North.

Metabolic traits differ across human populations also, causing disease related traits to occur such as high blood pressure, high triglycerides, or high cholesterol. A prominent example is the rising prevalence of type 2 diabetes. "It's been long proposed that it’s a [genetic] susceptibility to change in lifestyle and diet," Di Rienzo said.

There is a prevalence of inter-ethnic differences in disease and traits. Environmental risk factors clearly play a role in shaping differences. There is a growing conseus that genetic factors also contribute. Is there evidence for genetic – in addition to cultural and physiological – adaptations? How much of the phenotypic diversity is adaptive? What is the contribution of local adaptive traits?

These question led to many studies on signals based on haplotype structure such as lactase persistence, which is common in Europe and in agropastoralist populations, but rare elsewhere. The ability to digest milk in adult life became advantages with the introduction of animal farming, Di Rienzo said. Another example is the FY allele that is fixed in most sub-saharan Africa and is virtually absent everywhere else. FY codes for a chemokine receptor (antimalarial).

Selection for polygenic traits is expected to generate subtle changes in allele frequency at multiple loci. Standard approaches are unlikely to capture these signals. The signature of selection is for monogenic (small shifts) versus polygenic traits.

Her approach is for search of information about environmental selective pressures. She searches for correlations between alledle frequency and environmental variables. She takes into account the geographic structure of human populations shaping distribution.

She used a large dataset of more than 642,000 autosomal SNPs. Environmental variables included climate, ecoregion, and subsistence. Climate includes seasons, ecoregion with temperature, humidity. The genome-wide evidence for environmental adaptations is that most of the genome doesn’t contain genes or variants that affect the function of the genes.

Natural selection acts only on variants that have both functional and phenotypic effects. Is there an excess of test SNPs relative to control SNPs among those with lowest minimum p-values?

The test SNPs used are enriched for SNPs with functional effects. Control SNPs are unlikely to have functional effects (e.g. far from genes).

In all cases, a significant excess of the test relative to control SNPs indicating that environmentals select pressures shaped the geographic distribution of variation in the human genome.

The results suggested genome-wide evidence for environmental adaptations,” Di Rienzo said.

Pancreatic lipase-related protein 2 hydrolyzes galactolipids, is the main component in plants. The truncated PLRP2 protein, which occurs at a higher frequency in those populations with higher consumption of cereal grains. PLRP2 is associated with cereal rich diet.

Two examples of patterns at individual SNPs are “foraging” and “nonforaging” and she shows a slide with patterns showing differences in Africa, Europe and other. In each geographic location, there is a shift in allele frequency that allude to differences in diet of the populations.

The shift in allele frequency is not dramatic, but small. The top signals are with categorical variables like roots & tubers, foraging, polar ecoregion, and a dry ecoregion. Top climate variables have to do with seasons.

“Selection doesn’t act on genes, it acts on phenotypes. The phenotypes are enriched with signals for environmental correlations,” Di Rienzo said.

Disease classes are influenced by environmental selective pressures. Climate influenced cancer, CVD, immune, infection. Subsistence influenced metabolic and reproduction phenotypes. 

The overlaying signals of environmental correlations and genome-wide association studies show this flow:

SNP is affected by environmental correlations and GWAS, then selective pressures produce phenotype. It’s also known that pathogen diversity follows a gradient on climate factors, which can affect immune, autoimmune adaptations.

Di Rienzo made these conclusions from the data:

- Strong GWAS to climate, ecoregion and subsistence
- Signal of adaptation to environmental pressures are subtle, but consistent shifts in allele frequency
- Adaptation to local environ and common disease may have similar gene architecture
- Signals of climate correlations make a contribution to diseases of immune response and pigmentation traits

More information can be found at dbCLINE
READ MORE - How environmental change shaped human evolution