Bioinformatics

Bioinformatics
JIMMY CHENG-HO LIN
School of Medicine, Johns Hopkins University,
Baltimore, MD, USA
jimmy.lin@jhmi.edu
Synonyms
Computational biology; Biocomputing
Definition
Due the relative young age of the field, there have
been many definitions produced. While bioinformatics
purists emphasize the analysis of large-scale genomic
and transcriptomic data, looser definitions define bioinformatics
as any intersection of biology and computer
science including analysis of scientific literature, epidemiological
statistics, etc. Perhaps an inclusive definition
can be proposed:
The application of computational, statistical, and mathematical
methods to biological information to complement,
aid, and expedite scientific discovery and
enhance biological research. The three main aims
include:
1) DATABASE: acquisition, gathering, storage, organization
and management of large-scale data
2) ALGORITHM/TOOLS: development of algorithms
and computational tools to analyze and classify the
data
3) CONCLUSIONS/PREDICTIONS: process, abstract,
and integrate the data to make conclusions
and predictions
The data include and are not limited to nucleotide, proteomic,
genomic, phylogenetic, chemical, structural,
phenotypical, functional, ontological, and transcriptomic
information.
Basic Characteristics
Since the development of protein sequencing by Sanger
in 1955 and the Atlas of protein sequences by Margaret
Dayhoff in 1965, there has been a revolution of
high-throughput technologies that generate biological
information on an increasingly large scale. In August
2005, the International Nucleotide Sequence Database
Collaboration announced that the public collections of
DNA and RNA sequences had exceeded 100 gigabases
(or 100,000,000,000 bases, or “letters” of the genetic
code), which represent both individual genes and partial
and complete genomes of over 165,000 organisms.
In response to this deluge of data, computer scientists
and biologists collaborated in creating a new field of
study named bioinformatics.
Bioinformatics of Genomes
Bioinformatics is driven by high-throughput technologies.
In 1977, Fred Sanger introduced nucleotide/DNA
sequencing technology (Sanger et al. 1977) and by
1980, the first complete gene sequence for an organism
(FX174) was completed. In 1995, the first complete
 genome, H. influenze genome was completed. The
draft of the human genome was reported in 2001 and
completed in 2003. As of 2006, there are over 350 complete
genomes with over 450 more in progress. Bioinformatics
is thus necessary to organize and analyze all
this data.
Currently, the major databases for genomic information
include Genbank at NCBI, Ensembl at the European
Bioinformatics Institute, DNA Data Bank of Japan
at the National Institute of Genetics, and the UCSC
Genome Browser at UC Santa Cruz.
There are many computational tools and algorithms
that enabled the genomic revolution. Most notably, Jim
Kent’s GigAssembler (Kent 2001) program enabled the
consolidation of sequence information from over ten
labs to produce the draft human genome for the public
effort. A computational problem central to sequence
analysis is the alignment and comparison of sequences.
The program was first solved by Needleman-Wunsch
(Needleman 1970) and current implementations
are based on  multiple sequence alignment (MSA)
algorithm suite named Clustal (Higgins, Sharp 1988).
Another important problem has been the identification
of similar sequences in whole genomic and databases
searches. Current implementations that solve the problem
include BLAST (Altschul et al. 1990), PSI-Blast
(Altschul et al. 1997), and Blat (Kent 2002).
Bioinformatics of Transcriptomes
Besides large-scale sequencing, two other groups of
technologies have revolutionized bioinformatics, namely
transcriptomics ( transcriptome) and proteomics.
In 1995, two independent technologies were developed
to measure gene expression on a large-scale:  serial
analysis of gene expression (SAGE) (Velculescu et al.
1995) and microarray (Shena et al. 1995). By 1997, it
was possible to measure the entire transcriptional profile
of a complete Eukaryotic genome (Saccharomyces
cerevisiae) on a microarray chip (DeRisi et al. 1997).
Consolidated databases of gene expression include
Array Express repository at the EBI, Gene Expression
Omnibus at NCBI, mouse Gene Expression Database at
Jackson Laboratory, Sym Atlas with Novartis, and the
Stanford Microarray Database.
A large set of different algorithms were developed to
analyze these expression data.
Initial algorithms were based on clustering genes with
similar gene expression together ( clustering algorithms)
(Niehrs 1999) while programs incorporated later
methods such as  self organizing maps (Tamayo et
al. 1999),  bayesian networks (Friedman et al. 2000)
and  principal component analysis.
Bioinformatics of Proteomes
Since the development of protein sequencing in 1955
by Fred Sanger, protein research has greatly advanced.
The study of proteomics relies on technologies such
as two-dimensional gel electrophoresis and mass spectrometry
to identify the entire constitution of proteins
in an organism. The first  proteome was published in
1995 by Wasinger for the smallest known self-replicating
organism, Mycoplasma genitalium (Wasinger
et al. 1995). Yeast-two hybrid technology allowed
researchers to identify all the interactions between proteins.
Furthermore, as more and more crystal structures
were solved for the different proteins, in 1973, the
Brookhaven Protein Databank was created to store the
data.
The main databases for protein information include
Pfam (Bateman et al. 2000), UCSC Proteome Browser
(Hsu et al. 2004), Swiss-Prot, and UniProt (Wu et al.
2006) and many databases exist for specific proteins or
post-translational modifications. The major structural
genomics databases and classification schemes include
Protein DataBank (PDB) at Brookhaven National Labs,
Structural Classification of Proteins (SCOP) (Murzin et
al. 1995), CATH (Pearl et al. 2005) Protein Structure
Classification Database (UCL), and FSSP Database
(Holm, Sander 1996).
The major question in proteomic bioinformatics is the
in silico prediction of structure of proteins, also known
as the  protein folding problem. On all three levels
of primary, secondary, and tertiary structure, numerous
methods have been attempted such as comparative
modeling, threading, energyminimization, and ab initio
sequence methods. Various algorithms have also been
developed to query structure databases for similar structures, such as DALI Server at EBI and Vector Alignment
Search Tool (VAST) at NCBI.
Paradigm Shifts in Bioinformatics
In this post-genomic age, with the availability of
large amounts of information on all levels, biological
research is no longer confined to experimental methods
based on single genes. Now, investigators have a wealth
of information at their disposal. The new challenge is
to consolidate, integrate, evaluate, and obtain data from
established sources to generate hypotheses or produce
a set of targets that can then be validated and investigated
using experimental methods.
With more computation resources and more data available,
researcher can now start to think of genes and proteins
in relation to the vast network of interactions within
the genome and think more in terms of pathways
and systems. Just like biotechnological advances such
as PCR, Western blots, and microarrays have revolutionized
biology, future biological research will be intimately
involved with bioinformatics databases, tools,
and analyses.
Cross-References
 Bayesian Network
 Clustering Algorithms
 Genome
 Multiple Sequence Alignment
 Principal Component Analysis
 Protein Folding Problem
 Proteome
 Self-OrganizingMaps
 Serial Analysis of Gene Expression
 Transcriptome
References
Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990)
Basic local alignment search tool. J Mol Biol 215:403–410
Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller
W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST:
a new generation of protein database search programs. Nucl
Acids Res 25:3389–3402
Bateman A, Birney E, Durbin R, Eddy SR, Howe KL, Sonnhammer
EL (2000) The Pfam protein families database. Nucl
Acids Res 28:263–266
DeRisi JL, Iyer VR, Brown PO (1997) Exploring the metabolic
and genetic control of gene expression on a genomic scale.
Science 278(5338):680–686
Friedman N, Linial M, Nachman I, Pe’er D (2000) Using
Bayesian network to analyze expression data. In: Proc. 4th
Annu. Int. Conf. Computal. Mol. Biol. (RECOMB 2000).
Universal Academy Press, Tokyo, Japan, pp 127–135
Higgins DG, Sharp PM (1988) CLUSTAL: a package for performing
multiple sequence alignment on a microcomputer.
Gene 15;73(1):237–244
Holm L, Sander C (1996) Mapping the protein universe. Science
273:595–603
Hsu F, Pringle TH, Kuhn RM, Karolchik D, Diekhans M, Haussler
D, Kent WJ (2004) The UCSC Proteome Browser. Nucl
Acids Res 33(suppl 1):D454–D458
Kent WJ, Haussler D (2001) Assembly of the working draft
of the human genome with GigAssembler. Genome Res
11(9):1541–1548
Kent WJ (2002) BLAT–the BLAST-like alignment tool. Genome
Res 12(4):656–664
Lander et al (2001) Initial sequencing and analysis of the human
genome. Nature 15;409(6822):860–921
Murzin AG, Brenner SE, Hubbard T, Chothia C (1995) SCOP:
a structural classification of proteins database for the investigation
of sequences and structures. J Mol Biol 247:536–540
Needleman SB,Wunsch CD (1970) A general method applicable
to the search for similarities in the amino acid sequence of
two proteins. J Mol Biol 48:443–453
Niehrs C, Pollet N (1999) Synexpression groups in eukaryotes.
Nature 402:483–487
Pearl F, Todd A, Sillitoe I, Dibley M, Redfern O, Lewis T, Bennett
C, Marsden R, Grant A, Lee D, Akpor A, Maibaum
M, Harrison A, Dallman T, Reeves G, Diboun I, Addou S,
Lise S, Johnston C, Sillero A, Thornton J, Orengo C (2005)
The CATH Domain Structure Database and related resources
Gene3D and DHS provide comprehensive domain family
information for genome analysis. Nucl Acids Res 33:D247–
D251
Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing
with chain-terminating inhibitors. Proc Natl Acad Sci USA
74(12):5463–5467
Schena M, Shalon D, Davis RW, Brown PO (1995) Quantitative
monitoring of gene expression patterns with a complementary
DNA microarray. Science 270(5235):467–470
Tamayo P, Slonim D, Mesirov J, Zhu Q, Kitareewan S, Dmitrovsky
E et al (1999) Interpreting patterns of gene expression
with self-organizing maps: methods and application
to hematopoietic differentiation. Proc Natl Acad Sci USA
96:2907–2912
Velculescu VE, Zhang L, Vogelstein B, and Kinzler KW (1995)
Serial Analysis of Gene Expression. Science 270:484–487
Wasinger VC, Cordwell SJ, Cerpa-Poljak A, Yan JX, Gooley
AA, Wilkins MR, Duncan MW, Harris R, Williams
KL, Humphery-Smith I (1995) Progress with gene-product
mapping of the Mollicutes: Mycoplasma genitalium. Electrophoresis
16(7):1090–1094
Wu CH, Apweiler R, Bairoch A, Natale DA, Barker WC, Boeckmann
B, Ferro S, Gasteiger E, Huang H, Lopez R, Magrane
M, Martin MJ, Mazumder R, O’donovan C, Redaschi N,

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Aging and Health

Aging and Health
MICHAL ENGELMAN
Department of Population and Family Health Sciences,
Johns Hopkins University, Bloomberg School
of Public Health, Baltimore, MD, USA
mengelma@jhsph.edu
Synonyms
Elderly and health; Health of the elderly; Older people
and health
Definitions
Population aging, the demographic process by which
older persons become a proportionally larger share of
the total population, is associated with changing patterns
of mortality, morbidity, and disability (UNPD
2002). In the older population different aspects of
health have to be considered.  Gerontology, the scientific
study of the biological, psychological, and sociological
phenomena associated with old age and aging,
and geriatrics, the branch of medicine that focuses on
health promotion and the prevention and treatment of
disease and  disability in later life, both deal with the
well-being of older people.
Basic Characteristics
A gradual  demographic transition – from patterns of
high fertility and high mortality to patterns of lower fertility
and later mortality – has been underway across
the globe. Lower birth rates and growing longevity have
led to an overall increase in both the absolute number
and relative proportion of older people in the general
population. By 2002, the population of individuals 60
years and over reached 626 million, or 10 percent of
the total world population. Of these, nearly 70 million
are among the oldest-old, aged 80 or over. The older
population is projected to expand rapidly in the coming
decades, more than tripling its current size and reaching
2 billion by 2050. The oldest-old population is expected
to grow more than 5.5 times to reach 379 million by
2050. Decreasing fertility rates contribute to the prediction
that older individuals will at that time constitute 21
percent of the total world population, twice their current
proportion and equal to the number of predicted children.
The proportion of the oldest-old will quadruple
to 4 percent by the same year (UNPD 2003). Women
constitute the majority of older people in most countries
(Velkoff, Lawson 1998).
The demographic changes are linked with  epidemiologic
transitions, in particular a shift in the leading
causes of death away from infectious, acute diseases
in early life towards chronic and degenerative illnesses in mid- and later life. Given the increase in total
 life expectancy, a number of gerontological theories
addressing the implications of increased longevity for
population health have emerged, each proposing different
relationships between old-age mortality, morbidity,
and disability, or limitations in performing activities of
daily living. (For a review, see Agree, Freedman 1999)
The theories range from the most pessimistic – in which
delayed mortality is translated to increased years of life
with disease and disability – to the most optimistic, in
which morbidity and disability are compressed towards
the end of life, increasing the healthy proportion of
total life expectancy. More nuanced perspectives recognize
the complexity, mutability, and inter-connectedness
of the processes determining morbidity, disability,
and mortality, and suggests a continuous dynamic
relationship between them. International trends in mortality
and disability outcomes are mixed, supporting
a dynamic model of longevity and health in later life
that is influenced by a multitude of biomedical, environmental,
and social factors.
Population aging is an aggregate mark of human success
in reducing fertility, improving living conditions,
and curbing risks of death through innovations in public
health and medicine. However, insufficient preparedness
for the needs of an aging population on the part of
health and social service providers is a challenge confronting
societies at all levels of development.
Geriatric Health
Aging populations have higher rates of chronic disease
and  disability, and the likelihood of having multiple
co-morbidities rises significantly with age. In high
and low-income countries alike, ischemic heart disease
and cerebrovascular diseases are the leading causes of
death. In more developed nations, cancers (lung, colon,
rectum, stomach, and breast), chronic obstructive pulmonary
diseases, diabetes mellitus, and Alzheimer’s
Disease and other dementias are also among the most
prevalent causes of death. A range of chronic and
adult-onset conditions including depression, hearing
loss, alcohol-use disorders, osteoarthritis, schizophrenia,
bipolar disorders, and chronic obstructive pulmonary
diseases are among the leading causes of global
disability (Murray et al. 2001). Chronic diseases may
contribute to the gradual loss of senses such as sight
and hearing, to impaired mobility, to increased risks of
falls and fractures, and to disability in the performance
of activities of daily living.
As  senescence, or the slowing-down of physical systems
that takes place as the body ages, progresses,
a range of physical and mental capacities is weakened.
Age-related mental illness, especially dementia,
are particularly difficult to cope with for both patients
and caregivers alike. Dementia is a condition of irreversible
decline in cognition, functioning and behavior.
Alzheimer’s disease (AD) accounts for approximately
60–70% of dementia cases, with vascular dementia
accounting for the majority of the rest. The prevalence
of AD is estimated to be 8–15% in persons over 65. The
primary risk factor for dementia is age, with the prevalence
doubling for every 5-year age group after the age
of 65 and reaching as high as 39 percent after age 90
(Jorm, Jolley 1998).
Chronic diseases exact a heavy burden on older adults
due to associated long-term illness, diminished quality
of life, and increased health care costs. Although
the risk of disease and disability clearly increases with
advancing age, poor health is not an inevitable consequence
of aging. A healthy lifestyle (including regular
physical activity, a nutritious diet, and avoidance
of tobacco) is the recommended course for prevention.
Screening for early detection is also recommended for
those illnesses (e. g. some cancers, diabetes and its complications,
etc.) for which a course of treatment is available.
Aging and Pharmacotherapy
Older people are particularly susceptible to the risks of
medication use. Age-related loss of physiologic reserve
leads to pharmacokinetic changes and increases interindividual
variability. The loss of renal function, for
example, decreases the clearance of common drugs in
older people, while the loss of lean body mass and fat
mass leads to an altered volume of drug distribution.
Polypharmacy – the use of multiple (usually 5 or more)
medications – is a common issue since geriatric patients
frequently have multiple co-morbidities each treated
with one or more medication. Furthermore, some medications
bring about  side effects that then lead to
the prescription of additional drugs to treat the added
symptoms. Polypharmacy increases the potential of
drug interactions, adverse drug reactions, and the use
of inappropriate medications, or drugs that should be avoided in certain doses, disease states, or in combination
with other drugs (Hanlon et al. 2001).
Care-Giving
Historically, older people in need of assistance received
care from younger family members. However, previously
high levels of mortality and fertility meant that
the proportion of individuals reaching older ages was
relatively small while a larger pool of children and relatives
was available to share care-giving responsibilities.
More recently, the proportion of the population
at older ages has been expanding as the numbers of
younger family members available to provide care has
been shrinking.
Women – wives, daughters, daughters-in-law, nieces
and granddaughters – have traditionally provided the
bulk of family care-giving and continue to do so despite
rising levels of labor force participation. Older people
are as likely to provide care as they are to receive it,
and in developing and developed countries alike, spouses
are the main caregivers for both men and women.
Because of the sex differential in longevity, however,
women are more likely than men to find themselves
without a spouse and to be living alone when they need
care (Velkoff, Lawson 1998).
A relatively small proportion of older people – between
1 and 10 percent – reside in institutions in developed
nations (Velkoff, Lawson 1998). There has been growing
concern – though not much documentation – that as
networks of family caregivers shrink the rate of institutionalization
among older people may rise. Additional
concerns about the quality and cost of institutional care
are garnering attention in many countries.
Aging in Developing Nations
In developing nations a rapid  demographic transition
has outpaced economic development. Since 1980,
developing countries have been home to a larger proportion
of the world’s population of persons aged 60
and above than their industrialized counterparts (Lloyd-
Sherlock 2000). By 2000, 249 million people, or 59%
of the world’s 65 years of age and over population lived
in developing countries (US Census Bureau 2001).
According to demographic projections, by 2050, more
than three-quarters of the world’s older people will
be living in developing countries. By 2050 developing
countries will posses a similar age structure to
today’s more industrialized nations. Older people will
then comprise over 30% of the population in East Asia,
more than 20% of the population in Southern Asia and
Latin America, and approximately 10% of the population
in Africa (UNPD2003).
Though they are among the most disadvantaged populations
in developing nations, older people have not
been prioritized by international aid agencies. Eighty
percent of older people in developing countries have no
regular incomes, and approximately 100 million older
persons live on less than a dollar a day. Older people
in developing regions are often excluded from economic
development, healthcare and education programs
due to age limits and discrimination and humanitarian
agencies often fail to identify older people as a target
in the planning and delivery of services in conflict
areas (Help – Age International 2002). While incidence
of chronic and age-related disease has been rising
rapidly in developing nations, there is a lack of professionals
in geriatric medicine, preventing older adults
from receiving the health care they need (Keller et al.
2002).
Though norms of filial piety are still strong in many
developing countries, changes in family structures and
co-residence patterns are rendering traditional support
networks more vulnerable. Recognizing the need for
increased awareness and action on issues related to
global aging, the Second World Assembly on Aging
adopted the Madrid International Plan of Action in
2002. The Plan calls on governments, non-governmental
organizations, and the international community to
adopt the concept of “a society for all ages,” to end
age-based discrimination and abuse, and incorporate
the concerns of older people into national and international
economic and social development policies (United
Nations Programme on Ageing, 2002). The formation
of implementation andmonitoring strategies for the
Plan is now in progress.
Cross-References
 Age-Dependency Ratio
 Demographic Transition
 Disability
 Epidemiologic Transition
 Geriatrics
 Gerontology
 Life Expectancy
 Population Aging
 Senescence
References
Agree EM, Freedman VA (1999) Implications of Population
Aging for Geriatric Health. In: Gallo JJ (ed) Clinical Aspects
of Aging, 5th edn. Williams and Wilkins Inc., Baltimore,
MD, pp 659–669
Hanlon JT, Schmader KE, Ruby CM, Weinberger M (2001) Suboptimal
prescribing in older inpatients and outpatients. JAGS
49:200–209
HelpAge International (2002) State of the World’s Older People
2002. HelpAge International, London
Jorm AF, Jolley D (1998) The incidence of dementia: a metaanalysis.
Neurology 51:728–733
Keller I,Makipaa A, Kalenscher T, Kalache A (2002) Global Survey
on Geriatrics in the Medical Curriculum. World Health
Organization, Geneva
Lloyd-Sherlock P (2000) Old age and poverty in developing
countries: New policy challenges. World Development
28(12):2157–2168
Murray CJ, Lopez AD, Mathers CD, Stein C (2001) The Global
Burden of Disease 2000 Project: Aims, Methods and Data
Sources. World Health Organization, Geneva
United Nations Population Division (UNPD), Department of
Economic and Social Affairs (DESA) (2002) World Population
Ageing: 1950–2050. United Nations, New York
United Nations Population Division (UNPD), Department of
Economic and Social Affairs (DESA) (2003) World Population
Prospects: The 2002 Revision. United Nations, New
York
UN Programme on Ageing, Division for Social Policy and Development
(2002) Madrid International Plan of Action on Ageing.
United Nations, New York
U.S. Census Bureau (2001) Series P95/01–1, An Aging World:
2001. US Government Printing Office, Washington DC
Velkoff VA, Lawson VA (1998) Gender and Aging: Caregiving.
International Programs Center. U.S. Census Bureau, Washington
DC

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American Diets May Lack Vitamin D

A friend recently told me about how his uncle had heard that garlic could help lower his high blood pressure. So the uncle generously added garlic salt to his diet.

A little knowledge can kill you.

A similar misunderstanding appears to be spreading about vitamin D. More and more people are realizing that they are lactose intolerant. So they eliminate milk from their diets.

People also are worried about sun exposure and skin cancer, so they slop on sunscreen whenever they go out or otherwise avoid direct sunlight. And mercury is scaring folks away from eating fish.

As a result, some people are losing all sources of vitamin D. For the first time in a century, doctors are seeing a resurgence in rickets, that bone-deforming disease once endemic to wobbly-kneed child laborers in the Victorian era who never saw the light of day.

Pediatricians in Philadelphia have reported more than 150 new cases in the past three years, up from about zero. Washington, D.C., and other areas with large African-American populations are reporting the similar increases.

No formal studies have found the precise cause of the rickets — be it less milk consumption, less sun exposure, or other factors — but it does appear that Americans in general aren’t getting enough vitamin D.

Vitamin Q and A

Vitamin D is a complicated essential micronutrient. The National Institutes of Health convened a panel of experts last September to establish nutritional guidelines. As revealed in the official meeting proceedings, published in the August 2008 issue of the American Journal of Clinical Nutrition, they couldn’t come to any consensus. The published overview is essentially a collective shrug of the shoulders.

Vitamin D is crucial for calcium metabolism — namely, the making of strong bones — and likely for immune function, heart health, cell proliferation and cancer and diabetes protection, at a minimum. An independent study from Johns Hopkins University, published in the current issue of the Archives of Internal Medicine, associated lower levels of vitamin D in the blood with a higher risk of death.

Yet the experts couldn’t agree to any details. The current recommendation is to get 400 IU of vitamin D daily. Many say this isn’t enough, but no one knows how much more is too much.

Complicating issues further is the fact that vitamin D is the only nutrient that can be made entirely in the skin upon exposure to sunlight, yet this varies greatly with skin color and latitude. It’s hard to assess your daily dose. Few foods other than fish contain vitamin D. Milk is fortified with it, but you need four glasses to get 400 IUs.

Out of Africa

Lighter skin is more efficient at producing vitamin D. So African-Americans are at a double disadvantage for synthesizing vitamin D from sunlight — in the United States. Their darker skin blocks the ultraviolet light that triggers this chemical reaction. In their native lands, closer to the equator where sunlight is more direct, their darker skins would have enough sun exposure to synthesize vitamin D.

Peoples in high northern latitudes, such as Europeans, slowly developed lighter skin over tens of thousands of years to adapt to the weaker sunlight to generate enough vitamin D to survive. African-Americans forced migration from Africa occurred over a period of only a few hundred years.

Also, most African Americans — and most of the world, actually — are lactose intolerant and cannot digest cow milk well. So many do not drink enough milk. Natural sources of vitamin D include cod liver oil (as if anyone can stomach this, let alone find it outside their great-grandmother’s cupboard) and salmon and mackerel (tasty, but expensive).

In Philadelphia many rickets cases involve children of Black Muslims, and the culture of conservative clothing likely played a role.

Yet doctors wonder whether the African-American communities are providing a warning call for all of America, as kids of all races drink less milk, the primary albeit artificial source of vitamin D for most clothed, non-farming residents of North America.

Killer rays

More sunlight isn’t the answer. Humans evolved to frolic naked in the sun but also to live about 30 years or so in Africa. Take your fair skin better suited for Scandinavia and place it in Miami for several summers, and you’re going to get skin cancer.

Regardless, for latitudes north of New York City, and considering how people bundle up during winter, there’s not enough sunlight year-round to satisfy the daily vitamin D requirement.

Milk fortification works well. But all vitamin D supplementation and fortification is essentially created equal. Look for new vitamin D recommendations later this year that try to make sense of the ambiguous NIH report.

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Folate Scores Another Win: Brief, High Doses of Vitamin Blunt Damage from Heart Attack

Newswise — Long known for its role in preventing anemia in expectant mothers and spinal birth defects in newborns, the B vitamin folate, found in leafy green vegetables, beans and nuts has now been shown to blunt the damaging effects of heart attack when given in short-term, high doses to test animals.

In a new study, an international team of heart experts at Johns Hopkins and elsewhere report that rats fed 10 milligrams daily of folate, also known as folic acid or vitamin B9, for a week prior to heart attack had smaller infarcts than rats who took no supplements. On average, researchers say, the amount of muscle tissue exposed to damage and scarred by the arterial blockage was shrunk to less than a tenth.

The team’s findings, set for publication in the April 8 edition of the journal Circulation, come just weeks after other international studies in humans suggested that low-dose folic acid supplements may prevent dementia in the elderly and premature births.

“We want to emphasize that it is premature for people to begin taking high doses of folic acid,” says senior study investigator David Kass, M.D., a professor at The Johns Hopkins University School of Medicine and its Heart Institute.

“But if human studies prove equally effective, then high-dose folate could be given to high-risk groups to guard against possible heart attack or to people while they are having one,” says Kass.

The more likely and most practical advantage to ingesting supplements, he says, lies in folic acid’s potential to act as a short-term buffer for people who may be having a heart attack and who rush to their local emergency room complaining of chest pain.

Clinical trials are expected in the near future, although Kass says a major challenge in testing is that a high dose of folic acid for humans comparable to that given the rats would require an average-size adult to swallow more than 200 one-milligram pills per day, “an impractical and unrealistic regimen, even if the body excretes the excess.”

In addition, he cautions, “we do not yet know if folate is safe to consume in this high a dose, or how much or how little of it is needed to be effective,” citing 25 milligrams per day as the highest dose previously tested safe to consume in adults as.

Kass says that such large amount of folate may also yield unpredictable side effects. Some studies have linked the nutrient supplement to increased rates of colon and prostate cancer.

Each year, an estimated 565,000 first-time heart attacks occur in the United States, with an additional 300,000 recurrent heart attacks.

Results from the new study, conducted in rats - dozens were fed supplements and dozens more did not receive any - showed that overall pumping function during heart attack remained strong in vitamin B9-fortified animals.

The amount of blood pumped by the treated hearts during a 30-minute window when blood flow to the heart was restricted to simulate a heart attack stayed near normal for rodents, at an average ejection fraction of 73 percent. Meanwhile, it fell in the untreated group to 27 percent.

Similarly, the muscle wall at the front of the heart kept contracting during heartbeats, thickening by 37 percent in the supplement-fed group, but the muscle could barely compress, thickening by 5 percent, in the untreated group. (Sixty percent would be the normal amount of thickening in a healthy rat heart.)

Moreover, researchers found that an injection of folic acid into the bloodstream of rats that had never before taken supplements, within the first 10 minutes of a heart attack, was almost equally as effective as preventive therapy in reversing muscle damage, and in lowering infarct size by a factor of 10.

“Folic acid is already well known to be safe to consume in high doses in the short term, and it is very inexpensive, costing pennies per milligram, so its prospects look promising,” says Kass.

Researchers plan further tests to determine precisely why folate protects the heart, and to determine how effective it is in not-as-high doses. But they point out that it has long been known for its role in the normal workings of the cell’s principal energy source, the mitochondria, whose function is essential to maintaining healthy blood vessels.

It was this evidence that led to the latest study, which, says lead investigator An Moens, M.D., suggests that folate acts as an energy reserve in the heart, “providing much needed energy for muscle contraction, in the form of ATP, at the same time the heart is being starved for oxygen-carrying blood by a blocked artery.”

According to Moens, a postdoctoral cardiology research fellow at Johns Hopkins, study results showed that high-energy phosphate levels went down 43 percent in the blood of treated rats, but levels dropped by one-third more (by 66 percent) in untreated rats.

“With more fuel, the heart kept pumping even though its blood flow was reduced,” says Moens, now a cardiologist at the University of Antwerp in Belgium. “The smaller heart attacks seemed related to this better energy balance in the heart produced by the folate.”

In the study, heart function was monitored by more than two dozen key tests, such as echocardiogram and magnetic resonance imaging, as well as by blood analysis before, during and after the heart attack, when blood flow was allowed to resume in the coronary artery that had been blocked.

Among the team’s other findings that backed up the protective effects of folate on the heart were mild, slight dips in systolic blood pressure during heart attack in treated rats, while pressure fell in untreated animals by 25 percent. Similarly, blood flow was stable in the treated group, but dropped by 40 percent in untreated animals. Post-heart attack buildup of dangerous chemicals, known as reactive oxygen species, was halved in treated rats. And fatal arrhythmias, unstable heartbeats that can immediately follow a heart attack, also went down from 36.7 percent to 8.3 percent in the supplement-fed group.

“In future, we might just pop in an I.V., and give people high-dose folate while they are waiting for their catheterization or CT scans to search for blockages,” says Moens.

Funding for the study of folate, one of eight B vitamins, was provided by the National Institutes of Health and the Peter Belfer Laboratory Foundation, with additional support from the American Heart Association, the Belgian American Educational Foundations, as well as the University of Antwerp, Belgium.

In addition to Kass and Moens, other Hopkins researchers involved in this study were Hunter Champion, M.D., Ph.D.; Azeb Haile, M.S.; Muz Zviman, Ph.D.; Djahida Bedja, M.S.; Kathy Gabrielson, D.V.M., Ph.D.; Nazareno Paolocci, M.D., Ph.D. Kass is also the Abraham and Virginia Weiss Professor of Cardiology at Hopkins. Additional researchers from Belgium included Marc Claeys, M.D., Ph.D.; Dirk Borgonjon, M.S.; Luc Van Nassauw, Ph.D.; Floris Wuyts, Ph.D.; Rebecca Elsaesser, Ph.D.; Paul Cos, Ph.D.; Jean-Pierre Timmermans, Ph.D.; and Christiaan Vrints, M.D., Ph.D., from the University of Antwerp; and Barbara Tavazzi, M.D., Ph.D., and Guiseppe Lazzarino, M.D., Ph.D., from the University of Rome. Further assistance with biochemical analysis was provided by Pawel Kaminski, M.D., Ph.D., and Michael Wollin, M.D., Ph.D., both from the New York University School of Medicine.

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Vitamin B 9 may blunt heart attack damage

BALTIMORE, March 27 (UPI) — Folate — vitamin B 9 – potentially may be used to limit the damage of a heart attack, U.S. researchers say.The study, scheduled to be published in the April 8 edition of the journal Circulation, finds the vitamin blunted the damage from heart attack in animal studies.

“We want to emphasize that it is premature for people to begin taking high doses of folic acid,” senior study investigator Dr. David Kass, of The Johns Hopkins University School of Medicine in Baltimore says in a statement. “But if human studies prove equally effective, then high-dose folate could be given to high-risk groups to guard against possible heart attack or to people while they are having one.”

“We do not know how much or how little of it is needed to be effective,” Kass cautions. A large amount could yield unpredictable side effects and studies have linked folic acid supplements to increased rates of colon and prostate cancer, Kass says.

Folate — naturally found in leafy green vegetables, beans and nuts — is sometimes used as a general term to include folic acid — the form of vitamin B9 put in supplements and added to foods, especially grain products.

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