Thursday, April 28, 2011

How In Vitro Fertilization Works

In vitro fertilization (IVF) is the joining of a woman’s egg and a man’s sperm in a laboratory dish. In vitro means “outside the body.” Fertilization means the sperm has attached to and entered the egg.

A human ovum with corona radiata surrounding itNormally, an egg and sperm are fertilized inside a woman’s body. If the fertilized egg attaches to the lining of the womb and continues to grow, a baby is born about 9 months later. This process is called natural or unassisted conception.
IVF is a form of assisted reproductive technology (ART). This means special medical techniques are used to help a woman become pregnant. IVF has been successfully used since 1978. It is most often tried when other, less expensive fertility techniques have failed.

Indications

       IVF  is  indicated  when  alternative  treatments  are  either  unlikely  to  achieve  pregnancy  or  have  failed  to  result  in  pregnancy.      
        If  you  have  blocked  fallopian  tubes  or  extensive  pelvic  adhesions  preventing  your  egg  from  entering  the  fallopian  tubes,  IVF  is  indicated.
        If  you  have  severe  endometriosis  and  are  unable  to  conceive  in  spite  of   one  or  more  operations,  IVF would  offer  a  better  chance  of  conception.


        If  you  have  already  attempted  several  cycles  of  ovulation  induction  with  or  without  intra-uterine  insemination,  the  next  logical  step  is   to  move  on  to  IVF.
       If  your  husband’s  semen  shows  very  few  normal  moving  sperms,  too  few  to  be  able  to  fertilize  your  egg  in  the  normal  way  in  your  fallopian  tube,  IVF   ICSI  is  indicated.
        One  view  is  that  when  your  husband  has  sperms  that  are  less  than   5%   normal  forms,  less  than  5%  with  directional  movement  and  less  than  5  million  per  ml,  IVF  can  be  considered.
        If  your  husband  has  no  sperm  in  his  semen  but  has  live  sperm  in  his  testes or  epididymis,  these  can be  collected  by  a  Urologist,  stored  in  a  frozen  state  and  thawed  to  be  used  for  IVF  by  intra-cytoplasmic  sperm  injection  (ICSI ).

Factors to Consider

  • Age: Women younger than 35 years who do not have problems with their partners' sperm may try IVF.
  • Multiple births: Generally, in women who use IVF to establish a live birth, about 63% are single babies, 32% are twins, and 5% are triplets or more.
  • Cost: One cycle of IVF costs an average of  $12,000 - $17,000.
  • Reduced surgery: If a woman has IVF, she may not have to undergo surgery on her fallopian tubes. It is estimated that the IVF technique has reduced such surgeries by half.
  • Safety: Studies suggest that in vitro fertilization is safe. A recent study covered nearly 1,000 children conceived through these methods in 5 European countries and found that the children, monitored from birth to age 5 years, were as healthy as children conceived naturally. However, other studies have found a slightly increased risk of genetic disorders in children conceived through assisted reproductive technologies.

Technique

With in vitro fertilization, eggs are surgically aspirated from the woman's ovary under ultrasound guidance and mixed with sperm outside the body in a laboratory dish. After about 40 hours, the eggs are examined to see if they have become fertilized by the sperm and are dividing into cells. These fertilized eggs (now called embryos) are then placed in the women's uterus, thus bypassing the fallopian tubes where this process normally occurs.
IVF is now recognized worldwide as an established treatment for infertility.
This is how the procedure takes place:
  • The woman may be given certain drugs (hormones) to stimulate her ovaries to produce several eggs before the procedure to remove them.
  • A surgeon then inserts a needle through the vagina into the woman's ovary to remove eggs. This procedure used to be done with laparoscopic surgery, but the needle technique is much less invasive and much easier. General anesthesia is not required for this part of the procedure, but the woman may be given some sedating medication.
  • The fluid removed is examined in the laboratory to make sure eggs are present.
  • At the same time, the man provides a semen sample. He is asked not to have sexual intercourse for a few days before the eggs are retrieved from the woman and before he produces a semen sample (usually by masturbation). The sperm are separated from the semen in a laboratory procedure.
  • The active sperm are combined in the laboratory dish with the eggs. This may be referred to as in vitro fertilization.
  • About 18 hours after this fertilization procedure, it is possible to determine if the egg or eggs have been fertilized and have begun to grow as embryos. They are incubated and observed over the next 2-3 days or longer.
  • The doctor then transfers the embryos into the woman's uterus through the cervix with a catheter (a long slender tube). The woman should then remain in a resting position for the next hour or so.
  • She is given certain hormones for the next 2 weeks. If implantation works (the egg or eggs attach to the uterine wall and grow), the pregnancy test result is positive. 

Risks

  •     IVF requires a significant physical, emotional, financial, and time commitment. Stress and depression are common among couples dealing with infertility. A woman taking fertility medicines may have bloating, abdominal pain, mood swings, headaches, and other side effects. Many IVF medicines must be given by injection, often several times a day. (The health care team will teach the couple how to properly mix the medicines and give a shot.) Repeated injections can cause bruising.
  • In rare cases, fertility drugs may cause ovarian hyperstimulation syndrome (OHSS). This condition causes a build up of fluid in the abdomen and chest. Symptoms include abdominal pain, bloating, rapid weight gain (10 pounds within 3-5 days), decreased urination despite drinking plenty of fluids, nausea, vomiting, and shortness of breath. Mild cases can be treated with bed rest. More severe cases require draining of the fluid with a needle.
  • Medical studies to date have concluded that fertility drugs are not linked to ovarian cancer.
  • Risks of egg retrieval include reactions to anesthesia, bleeding, infection, and damage to structures surrounding the ovaries, including the bowel and bladder.
  • There is a risk of multiple pregnancies when more than one embryo is placed into the womb. Carrying more than one baby at a time increases the risk of premature birth and low birth weight. (However, even a single baby born after IVF is at higher risk for prematurity and low birth weight.) It is unclear whether IVF increases the risk of birth defects.

Outlook (Prognosis)

After embryo transfer, the woman may be told to rest for the remainder of the day. Complete bed rest is not necessary, unless there is an increased risk of OHSS. Most women return to normal activities the next day.
Women who undergo IVF must take daily shots or pills of the hormone progesterone for 8 - 10 weeks after the embryo transfer. Progesterone is a hormone produced naturally by the ovaries that helps thicken the lining of the womb (uterus). This makes it easier for the embryo to implant. Too little progesterone during the early weeks of pregnancy may result in a miscarriage.
About 12 -14 days after the embryo transfer, the woman will return to the clinic so that a pregnancy test can be done. (See: hCG quantitative test)
Call your health care provider right away if you had IVF and have:
  • A fever over 100.5 F (38 C)
  • Pelvic pain
  • Heavy bleeding from the vagina
  • Blood in the urine

Other assisted reproduction techniques

The following procedures have been used as alternatives to IVF but are not discussed in detail here:
  • Gamete intrafallopian transfer (GIFT): GIFT is similar to IVF. It is used when a woman has at least one normal Fallopian tube. Eggs are placed in this tube along with a man's sperm to fertilize there.
  • Zygote intrafallopian transfer (ZIFT): ZIFT is tubal embryo transfer in which a woman's eggs are taken from her ovaries, fertilized in the laboratory, and put back in the fallopian tubes rather than the uterus.
  • Assisted fertilization techniques when not enough sperm are available or sperm quality is not sufficient to fertilize include the following:
    • Partial zona dissection
    • Subzonal sperm injection
    • Intracytoplasmic sperm injection

  • Embryo cryopreservation (frozen fertilized egg and sperm)
Source:

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Saturday, April 16, 2011

Six Common Misconceptions about Immunization

This list of six common misconceptions was originally written by the Centers for Disease Control and Prevention in the United States primarily for use by practitioners giving vaccinations to children in their practices.

An edited version is reproduced here as useful information for health-care workers giving vaccination as well as concerned parents. In this modern age of communication, health-care workers will encounter patients who have reservations about getting vaccinations for themselves or their children. There can be many reasons for fear of or opposition to vaccination. Some people have religious or philosophic objections. Some see mandatory vaccination as interference by the government into what they believe should be a personal choice. Others are concerned about the safety or efficacy of vaccines, or may believe that vaccine-preventable diseases do not pose a serious health risk.

All health-care workers giving vaccines have a responsibility to listen to and try to understand a patient's concerns, fears, and beliefs about vaccination and to take them into consideration when offering vaccines. These efforts will not only help to strengthen the bond of trust between staff and patient but will also help determine which, if any, arguments might be most effective in persuading these patients to accept vaccination.
These pages address six common misconceptions about vaccination that are often cited by concerned parents as reasons to question the wisdom of having their children vaccinated. If staff can respond with accurate rebuttals perhaps we can not only ease parents' minds on these specific issues but discourage them from accepting other anti-vaccine "facts" at face value. The goal of health care providers is not to browbeat parents into vaccinating, but to make sure they have accurate information with which to make an informed decision.


1. "Diseases had already begun to disappear before vaccines were introduced, because of better hygiene and sanitation."

Statements like this are very common in anti-vaccine literature, the intent apparently being to suggest that vaccines are not needed. Improved socioeconomic conditions have undoubtedly had an indirect impact on disease. Better nutrition, not to mention the development of antibiotics and other treatments, have increased survival rates among the sick; less crowded living conditions have reduced disease transmission; and lower birth rates have decreased the number of susceptible household contacts. But looking at the actual incidence of disease over the years can leave little doubt of the significant direct impact vaccines have had, even in modern times.
For example, there have been periodic peaks and valleys throughout the years, but the real, permanent drop in measles incidence coincided with the licensure and wide use of measles vaccine beginning in 1963.
Other vaccine-preventable diseases show a roughly similar pattern in incidence, with all except hepatitis B showing a significant drop in cases corresponding with the advent of vaccine use. (The incidence of hepatitis B has not dropped as much because infants vaccinated in routine programs will not be at high risk of disease until they are at least teenagers. Therefore a 15-year lag can be expected between the start of routine infant vaccination and a significant drop in disease incidence.) Haemophilus influenzae type b (Hib) vaccine is another good example, because Hib disease was prevalent until the early- to mid- 1990s, when conjugate vaccines that can be used for infants were finally developed. (The polysaccharide vaccine previously available could not be used for infants, in whom most cases of the disease were occurring.)

Are we expected to believe that better sanitation caused incidence of each disease to drop just at the time a vaccine for that disease was introduced? Since sanitation is not better now than it was in 1990, it is hard to attribute the virtual disappearance of Hib disease in children in recent years in countries with routine Hib vaccination (from an estimated 20,000 cases a year to 1,419 cases in 1993, and dropping in the United States of America) to anything other than the vaccine.

Finally, we can look at the experiences of several developed countries after they allowed their immunization levels to drop. Three countries —Great Britain, Sweden and Japan — cut back the use of pertussis (whooping cough) vaccine because of fear about the vaccine. The effect was dramatic and immediate. In Great Britain, a drop in pertussis vaccination in 1974 was followed by an epidemic of more than 100,000 cases of pertussis and 36 deaths by 1978. In Japan, around the same time, a drop in vaccination rates from 70% to 20%-40% led to a jump in pertussis from 393 cases and no deaths in 1974 to 13,000 cases and 41 deaths in 1979. In Sweden, the annual incidence rate of pertussis per 100,000 children of 0-6 years of age increased from 700 cases in 1981 to 3,200 in 1985.
It seems clear from these experiences that not only would diseases not be disappearing without vaccines, but if we were to stop vaccinating, they would come back. Of more immediate interest is the major epidemics of diphtheria that occurred in the former Soviet Union in the 1990s, where low primary immunization rates for children and the lack of booster vaccinations for adults resulted in an increase from 839 cases in 1989 to nearly 50,000 cases and 1,700 deaths in 1994. There were at least 20 imported cases in Europe and two cases in U.S. citizens who had worked in the former Soviet Union.

2. "The majority of people who get disease have been vaccinated."

This is another argument frequently found in anti-vaccine literature, the implication being that this proves that vaccines are not effective. In fact it is true that in an outbreak those who have been vaccinated often outnumber those who have not — even with vaccines such as measles, which we know to be about 98% effective when used as recommended.
This apparent paradox is explained by two factors. First, no vaccine is 100% effective. To make vaccines safer than the disease, the bacteria or virus is killed or weakened (attenuated). For reasons related to the individual, not all vaccinated persons develop immunity. Most routine childhood vaccines are effective for 85% to 95% of recipients. Second, in a country such as the United States the people who have been vaccinated vastly outnumber those who have not.
How these two factors work together to result in outbreaks in which the majority of cases have been vaccinated can be more easily understood by looking at a hypothetical example: "in a high school of 1,000 students, none has ever had measles. All but five of the students have had two doses of measles vaccine, and so are fully immunized. The entire student body is exposed to measles, and every susceptible student becomes infected. The five unvaccinated students will be infected, of course. But of the 995 who have been vaccinated, we would expect several not to respond to the vaccine. The efficacy rate for two doses of measles vaccine can be as high as >99%. In this class, seven students do not respond, and they, too, become infected. Therefore seven of 12, or about 58%, of the cases occur in students who have been fully vaccinated."
As you can see, this doesn't prove the vaccine didn't work — only that most of the children in the class had been vaccinated, so those who were vaccinated and did not respond outnumbered those who had not been vaccinated. Looking at it another way, 100% of the children who had not been vaccinated got measles, compared with less than 1% of those who had been vaccinated. Measles vaccine protected most of the class; if nobody in the class had been vaccinated, there would probably have been 1,000 cases of measles.
WHO gratefully acknowledges the permission of CDC Atlanta, to present an edited version of "Six common misconceptions about immunization".

3. "There are "hot lots" of vaccine that have been associated with more adverse events and deaths than others. Parents should find the numbers of these lots and not allow their children to receive vaccines from them."

This misconception often receives considerable publicity. First of all, the concept of a "hot lot" of vaccine as it is used in this context is wrong. It is based on the presumption that the more reports of adverse events a vaccine lot is associated with, the more dangerous the vaccine in that lot; and that by consulting a list of the number of reports per lot, a parent can identify vaccine lots to avoid.
This is misleading for two reasons:
  • Most surveillance systems report events that are temporally associated with receipt of vaccine; these reports should not be interpreted to imply causality. In other words, an adverse report following vaccination does not mean that the vaccine caused the event. Statistically, a certain number of serious illnesses, even deaths, can be expected to occur by chance alone among children recently vaccinated. Although vaccines are known to cause minor, temporary side effects such as soreness or fever, there is little, if any, evidence linking vaccination with permanent health problems or death. The point is that just because an adverse event has been reported by the surveillance system, it does not mean it was caused by a vaccine.
  • Vaccine lots are not the same. The sizes of vaccine lots might vary from several hundred thousand doses to several million, and some are in distribution much longer than others. Naturally a larger lot or one that is in distribution for a longer period will be associated with more adverse events, simply by chance. Also, more coincidental deaths are associated with vaccines given in infancy than later in childhood, since the background death rates for children are highest during the first year of life. So knowing that lot A has been associated with x number of adverse events while lot B has been associated with y number would not necessarily say anything about the relative safety of the two lots, even if the vaccine did cause the events. Reviewing published lists of "hot lots" will not help parents identify the best or worst vaccines for their children. If the number and type of adverse event reports for a particular vaccine lot suggested that it was associated with more serious adverse events or deaths than are expected by chance, most countries have a system which results in the lot being recalled. All vaccines purchased through the UNICEF vaccine procurement system meet World Health Organization standards for safety and quality of production.
 

4. "Vaccines cause many harmful side effects, illnesses, and even death - not to mention possible long-term effects we don't even know about."

Vaccines are actually very safe, despite implications to the contrary in many anti-vaccine publications. Most vaccine adverse events are minor and temporary, such as a sore arm or mild fever. These can often be controlled by taking paracetamol after vaccination. More serious adverse events occur rarely (on the order of one per thousands to one per millions of doses), and some are so rare that risk cannot be accurately assessed. As for vaccines causing death, again so few deaths can plausibly be attributed to vaccines that it is hard to assess the risk statistically. Each death reported to ministries of health is generally thoroughly examined to assess whether it is really related to administration of vaccine, and if so, what exactly is the cause. When, after careful investigation, an event is felt to be a genuine vaccine-related event, it is most frequently found to be a programmatic error, not related to vaccine manufacture.

Diphtheria-tetanus-pertussis (DTP) vaccine and Sudden Infant Death Syndrome (SIDS)

One myth that won't seem to go away is that DTP vaccine causes sudden infant death syndrome (SIDS). This belief came about because a moderate proportion of children who die of SIDS have recently been vaccinated with DTP; on the surface, this seems to point toward a causal connection. This logic is faulty however; you might as well say that eating bread causes car crashes, since most drivers who crash their cars could probably be shown to have eaten bread within the past 24 hours.
If you consider that most SIDS deaths occur during the age range when three shots of DTP are given, you would expect DTP shots to precede a fair number of SIDS deaths simply by chance. In fact, when a number of well-controlled studies were conducted during the 1980s, the investigators found, nearly unanimously, that the number of SIDS deaths temporally associated with DTP vaccination was within the range expected to occur by chance. In other words, the SIDS deaths would have occurred even if no vaccinations had been given.
In fact, in several of the studies, children who had recently received a DTP shot were less likely to get SIDS. The Institute of Medicine reported that "all controlled studies that have compared immunized versus non-immunized children have found either no association . . . or a decreased risk . . . of SIDS among immunized children" and concluded that "the evidence does not indicate a causal relation between [DTP] vaccine and SIDS."
Looking at risk alone is not enough however - you must always look at both risks and benefits. Even one serious adverse effect in a million doses of vaccine cannot be justified if there is no benefit from the vaccination. If there were no vaccines, there would be many more cases of disease, and along with them, more serious side effects and more deaths. For example, according to an analysis of the benefit and risk of DTP immunization, if there was no immunization program in the United States, pertussis cases could increase 71-fold and deaths due to pertussis could increase four-fold. Comparing the risk from disease with the risk from the vaccines can give us an idea of the benefits we get from vaccinating our children.

Risk from disease versus risk from vaccines


DISEASE VACCINES
Measles MMR
Pneumonia: 1 in 20 Encephalitis or severe allergic reaction: 1 in 1 million
Encephalitis: 1 in 2 000
Death: 1 in 3 000 in industrialized countries. As much as 1 in 5 in outbreaks in developing countries
Mumps
Encephalitis: 1 in 300
Rubella
Congenital Rubella Syndrome: 1 in 4 (if woman becomes infected in early pregnancy)
Diphtheria DTP
Death: 1 in 20 Continuous crying, then full recovery: 1 in 100
Tetanus Convulsions or shock, then full recovery: 1 in 1 750
Death: 25-70 in 100 overall. 10-20 in 100 with good intensive care management Acute encephalopathy: 0-10.5 in 1 000 000
Pertussis Death: None proven
Pneumonia: 1 in 8
Encephalitis: 1 in 20
Death: 1 in 200
The fact is that a child is far more likely to be seriously injured by one of these diseases than by any vaccine. While any serious injury or death caused by vaccines is too many, it is also clear that the benefits of vaccination greatly outweigh the slight risk, and that many, many more injuries and deaths would occur without vaccinations. In fact, to have a medical intervention as effective as vaccination in preventing disease and not use it would be unconscionable.


5. "Vaccine-preventable diseases have been virtually eliminated from my country, so there is no need for my child to be vaccinated."

It is true that vaccination has enabled us to reduce most vaccine-preventable diseases to very low levels in many countries. However, some of them are still quite prevalent — even epidemic — in other parts of the world. Travellers can unknowingly bring these diseases into any country, and if the community were not protected by vaccinations, these diseases could quickly spread throughout the population, causing epidemics there.
At the same time, the relatively few cases that a country may currently have could very quickly become tens or hundreds of thousands of cases without the protection given by vaccines. We should therefore still be vaccinated, for two reasons.
The first is to protect ourselves. Even if we think our chances of getting any of these diseases are small, the diseases still exist and can still infect anyone who is not protected.
The second is to protect those around us. There is a small number of people who cannot be vaccinated (because of severe allergies to vaccine components, for example), and a small percentage of people don't respond to vaccines. These people are susceptible to disease, and their only hope of protection is that people around them are immune and cannot pass disease on to them. A successful vaccination program, like a successful society, depends on the cooperation of every individual to ensure the good of all. We would think it irresponsible of a driver to ignore all traffic regulations on the presumption that other drivers will watch out for him or her. In the same way we shouldn't rely on people around us to stop the spread of disease; we, too, must do what we can.


6. "Giving a child multiple vaccinations for different diseases at the same time increases the risk of harmful side effects and can overload the immune system".

Children are exposed to many foreign antigens every day. Eating food introduces new bacteria into the body, and numerous bacteria live in the mouth and nose, exposing the immune system to still more antigens. An upper respiratory viral infection exposes a child to four to ten antigens, and a case of "strep throat" to 25 - 50. According to "Adverse events Associated with childhood vaccines", a 1994 report from the Institute of Medicine in the United States, "In the face of these normal events, it seems unlikely that the number of separate antigens contained in childhood vaccines . . . would represent an appreciable added burden on the immune system that would be immuno-suppressive."
Indeed, available scientific data show that simultaneous vaccination with multiple vaccines has no adverse effect on the normal childhood immune system.
A number of studies and reviews have been conducted to examine the effects of giving various combinations of vaccines simultaneously. These studies have shown that the recommended vaccines are as effective in combination as they are individually, and that such combinations carry no greater risk for adverse side effects.
Research is under way to find ways to combine more antigens in a single vaccine injection (for example, measles, mumps, rubella (MMR) and chickenpox). This will provide all the advantages of the individual vaccines, but will require fewer shots. There are two practical factors in favour of giving a child several vaccinations during the same visit. First, we want to immunize children as early as possible to give them protection during the vulnerable early months of their lives. This generally means giving inactivated vaccines beginning at two months and live vaccines at 12 months. The various vaccine doses thus tend to fall due at the same time. Second, giving several vaccinations at the same time will mean fewer clinic visits for vaccinations, which saves parents both time and money and may be less traumatic for the child. In countries where there is a likelihood of reduced contact with the health care system, there is an added advantage of ensuring that there are no missed opportunities to complete the recommended vaccinations for a child.

WHO gratefully acknowledges the permission of CDC Atlanta, to present an edited version of "Six common misconceptions about immunization".

Source: WHO.int
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Wednesday, April 6, 2011

Vitamin D and Reducing Cancer Risk

             Given that the potential role of vitamin D in cancer prevention has been widely touted, many people were surprised that cancer-related considerations didn't figure prominently in the new Dietary Reference Intakes for vitamin D established by the Institute of Medicine (IOM). An IOM committee on which we served, charged with determining the population needs for vitamin D in North America, reviewed the evidence linking vitamin D with both skeletal and nonskeletal health outcomes. The committee concluded that vitamin D plays an important role in bone health and that the evidence provides a sound basis for determining the population's needs. For outcomes beyond bone health, however, including cancer, cardiovascular disease, diabetes, and autoimmune disorders, the evidence was found to be inconsistent and inconclusive as to causality.

             Based on vitamin D's importance to bone health, the recommended dietary allowances (RDAs) are 600 IU per day for persons 1 to 70 years of age and 800 IU per day for persons over 70 — intakes corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng per milliliter (50 nmol per liter). Because of wide variation in skin synthesis of vitamin D and the known risks of skin cancer, we derived the RDAs under the assumption that sun exposure would be minimal. The committee also concluded that the prevalence of vitamin D inadequacy in North America has been overestimated. Most North Americans have serum 25-hydroxyvitamin D concentrations above 20 ng per milliliter, which is adequate for bone health in at least 97.5% of the population.
Key Points
  • Vitamin D is essential for the formation, growth, and repair of bones and for normal calcium absorption and immune function. It is obtained primarily through exposure of the skin to ultraviolet radiation in sunlight, but it can also be obtained from some foods and dietary supplements (see Questions 1 and 4).
  • Some studies suggest that higher intakes of vitamin D from food and/or supplements and higher levels of vitamin D in the blood are associated with reduced risks of colorectal cancer; however, the research results overall have been inconsistent (see Question 7).
  • Whether vitamin D is associated with reduced risks of other cancers, including breast, prostate, and pancreatic cancers, remains unclear (see Questions 8, 9, 10, and 11).
  • The National Cancer Institute (NCI) does not recommend for or against the use of vitamin D supplements to reduce the risk of colorectal or any other type of cancer (see Question 14).

    Note: The information in this fact sheet is not to be used as the basis for making health claims about products containing vitamin D.

  • What is vitamin D?
  • How much vitamin D is needed for health?
  • What are the health effects of vitamin D deficiency?
  • How much vitamin D is in fortified foods and supplements?
  • Is it safe to take vitamin D supplements?
  • Is there a role for vitamin D in reducing cancer risk?
  • Is there evidence that vitamin D can help reduce the risk of colorectal cancer?
  • Is there evidence that vitamin D can help reduce breast cancer risk?
  • Is there evidence that vitamin D can help reduce prostate cancer risk?    
  • Is there evidence that vitamin D can help reduce pancreatic cancer risk?
  • Is there evidence that vitamin D can help reduce the risk of other rare cancers?
  • What are the possible mechanisms by which vitamin D may modify cancer risk?
  • How can people get enough sunlight for vitamin D synthesis while minimizing the risk of skin cancer?
  • Does NCI recommend the use of vitamin D supplements to prevent colorectal or other cancers?         
  1. What is vitamin D?
    Vitamin D is technically not a vitamin. It is the name given to a group of fat-soluble prohormones (substances that are precursors to hormones that usually have little hormonal activity by themselves). Two major forms of vitamin D that are important to humans are vitamin D2, or ergocalciferol, and vitamin D3, or cholecalciferol. Vitamin D2 is made naturally by plants, and vitamin D3 is made naturally by the body when the skin is exposed to ultraviolet radiation (in particular, UVB radiation) in sunlight. Vitamin D2 and vitamin D3 can also be commercially manufactured. The active form of vitamin D in the body is 1,25-dihydroxyvitamin D, or calcitriol, which can be made from either vitamin D2 or vitamin D3. To make the active form, vitamin D2 and vitamin D3 are modified in the liver to produce 25-hydroxyvitamin D, which travels through the blood to the kidneys, where it is modified further to make 1,25-dihydroxyvitamin D.
    Vitamin D is involved in a number of processes that are essential for good health, including the following:
    • It helps improve muscle strength and immune function.
    • It helps reduce inflammation.
    • It promotes the absorption of calcium from the small intestine.
    • It helps maintain adequate blood levels of the calcium and phosphate needed for bone formation, mineralization (incorporating minerals to increase strength and density), growth, and repair (1–3).
    Most people get the vitamin D they need through sunlight exposure. It can also be obtained through the diet, but very few foods naturally contain vitamin D. These foods include fatty fish, fish liver oil, and eggs. Smaller amounts are found in meat and cheese. Most dietary vitamin D comes from fortified foods, such as milk, juices, yogurt, bread, and breakfast cereals. Vitamin D can also be obtained through dietary supplements. Fortified foods and dietary supplements usually contain either vitamin D2 or vitamin D3. A person’s vitamin D status is usually checked by measuring the level of 25-hydroxyvitamin D in their blood serum.
  2. How much vitamin D is needed for health?
    A serum level of 25-hydroxyvitamin D lower than 15 nanograms per milliliter (ng/mL)—equivalent to 37.5 nanomoles per liter (nmol/L)—is generally considered inadequate for a healthy person to maintain bone health and normal calcium metabolism (2). However, some experts say that this may be on the low side, and the 2005 Dietary Guidelines for Americans notes that the optimal level may be as high as 80 nmol/L. A serum level below 11 ng/mL (27.5 nmol/L) is consistent with vitamin D deficiency in infants, neonates, and young children (2). The Institute of Medicine of the National Academies has developed the following recommended daily intakes of vitamin D (on the assumption that vitamin D3 is not being made in the skin through sun exposure) (1, 2):

    Age
    Recommended Minimum Vitamin D
    Intake (μg/day and IU/day)
    Birth to 50 years
    5 μg (=200 IU)
    51–70 years
    10 μg (=400 IU)
    71+ years
    15 μg (=600 IU)
    Pregnancy
    5 μg (=200 IU)
    Lactation
    5 μg (=200 IU)
    μg = microgram; 1 μg = 40 International Units (IU) The 2005 Dietary Guidelines for Americans recommends that older adults, people with dark skin, and people exposed to insufficient sunlight should consume extra vitamin D from vitamin D-fortified foods and/or supplements.
    People are more likely to not get enough vitamin D than to get too much. However, excessive intake of any nutrient, including vitamin D, can cause toxic effects (see Question 5). Excessive sun exposure does not cause vitamin D toxicity.

  3. What are the health effects of vitamin D deficiency? Vitamin D deficiency can impair normal bone metabolism, leading to the following conditions:
    • Rickets (a condition in children marked by soft and deformed bones; it is caused by undermineralization of bone).
    • Osteomalacia (adult rickets).
    • Osteoporosis (weak and porous bones) (1, 2).
  4. How much vitamin D is in fortified foods and supplements?
    Fortification of foods with vitamin D in the United States is carefully regulated (4). Vitamin D fortification is allowed for milk and milk products, cereal flours and related products, margarine, soy-based food products, and fruit juices and fruit juice drinks. Milk is usually fortified with 2.5 μg (100 IU) vitamin D per cup (4). Some yogurts are now fortified with vitamin D. Cheese, ice cream, and other dairy products made from milk are generally not fortified with vitamin D. To see if a food product has been fortified, check the food label.

    The amount of vitamin D in multivitamins and other dietary supplements typically ranges from 10 μg (400 IU) to 50 μg (2,000 IU) (5).
  5. Is it safe to take vitamin D supplements?
    Vitamin D toxicity is more likely to occur from high intakes of dietary supplements than from high intakes of vitamin D-fortified foods. For most children and adults, the tolerable upper intake level (UL) of vitamin D intake from foods and supplements is 25 μg (1,000 IU) per day for those less than 1 year of age and 50 μg (2,000 IU) per day for older individuals (1, 2). The UL is the highest level of daily intake (from all sources combined) that is likely to pose no risk of adverse effects for almost all people.

    Excessive vitamin D intake is toxic because it increases calcium levels. Increased calcium levels can lead to calcinosis (the deposit of calcium salts in soft tissues of the body, such as the kidneys, heart, and lungs) and hypercalcemia (high blood levels of calcium). Symptoms of excessive vitamin D intake may include heart rhythm abnormalities; mental status changes, such as confusion; pain; conjunctivitis; anorexia; fever; chills; thirst; vomiting; and weight loss (1, 2, 4).
  6. Is there a role for vitamin D in reducing cancer risk? A large number of scientific studies have investigated a possible role for vitamin D in cancer prevention.
    • The first results came from epidemiologic studies known as geographic correlation studies. In these studies, an inverse relationship was found between sunlight exposure levels in a given geographic area and the rates of incidence and death for certain cancers in that area. Individuals living in southern latitudes were found to have lower rates of incidence and death for these cancers than those living at northern latitudes. Because sunlight/UV exposure is necessary for the production of vitamin D3, researchers hypothesized that variation in vitamin D levels accounted for the observed relationships.
    • Evidence of a possible cancer-protective role for vitamin D has also been found in laboratory studies of the effect of vitamin D treatment on cancer cells in culture. In these studies, vitamin D promoted the differentiation and death (apoptosis) of cancer cells, and it slowed their proliferation.
    • Randomized clinical trials designed to investigate the effects of vitamin D intake on bone health have suggested that higher vitamin D intakes may reduce the risk of cancer. One study involved nearly 1,200 healthy postmenopausal women who took daily supplements of calcium (1,400 mg or 1,500 mg) and vitamin D (25 μg vitamin D, or 1,100 IU―a relatively large dose) or a placebo for 4 years. The women who took the supplements had a 60 percent lower overall incidence of cancer (6); however, the study did not include a vitamin D-only group. Moreover, the primary outcome of the study was fracture incidence; it was not designed to measure cancer incidence. This limits the ability to draw conclusions about the effect of vitamin D intake on cancer risk.
    • A number of observational studies have investigated whether people with higher vitamin D levels or intake have lower risks of specific cancers, particularly colorectal cancer and breast cancer. Associations of vitamin D with risks of prostate, pancreatic, and other, rarer cancers have also been examined. These studies have yielded inconsistent results, most likely because of the challenges of conducting observational studies of diet (7). Information about dietary intakes is obtained from the participants through the use of food frequency questionnaires, diet records, or interviews in which the participants are asked to recall information about their dietary intakes. Information collected in this manner can be inaccurate. In addition, only recently has a comprehensive food composition database with vitamin D values for the U.S. food supply become available. Other dietary components or energy balance may also modify vitamin D metabolism (8). Measuring blood levels of 25-hydroxyvitamin D to determine vitamin D status avoids some of the limitations of assessing dietary intake. However, vitamin D levels in the blood vary by race, with the season, and possibly with the activity of genes whose products are involved in vitamin D transport and metabolism. These variations complicate the interpretation of studies that measure the concentration of vitamin D in serum at a single point in time.
      Finally, it is difficult to separate the effects of vitamin D and calcium because of the complicated biological interactions between these substances. To fully understand the effect of vitamin D on cancer and other health outcomes, new randomized trials will need to be carried out (9). However, the appropriate dose of vitamin D to use in such trials is still not clear (10).

  7. Is there evidence that vitamin D can help reduce the risk of colorectal cancer? Epidemiologic studies of the association between vitamin D and the risk of colorectal cancer have provided some indications that higher levels of intake are associated with a reduced risk. However, the data are inconsistent.
    In the American Cancer Society’s Cancer Prevention Study (CPS) II Nutrition Cohort, the diet, medical history, and lifestyle of more than 120,000 men and women were analyzed (11). Men who had the highest intakes of vitamin D through both their diet and supplement use (greater than 13 μg, or 525 IU, per day) had a slightly lower risk of colorectal cancer than men who had the lowest vitamin D intakes. However, this association was not observed among women.
    In a pooled analysis of data from 10 cohort studies (including the CPS II cohort), individuals with the highest dietary vitamin D intakes had a slightly lower risk of colorectal cancer than those with the lowest intakes, but the reduction in risk was not statistically significant (12).
    In the Women’s Health Initiative randomized trial, healthy postmenopausal women took daily supplements that contained both calcium (1,000 mg) and vitamin D (10 μg, or 400 IU) or a placebo for an average of 7 years. Supplementation did not reduce the incidence of colorectal cancer (13). However, some scientists have raised the possibility that the relatively low level of vitamin D supplementation and the short duration of participant follow-up might account for the negative results.
    At least one epidemiologic study has reported an association between vitamin D and reduced mortality from colorectal cancer. Among the 16,818 participants in the Third National Health and Nutrition Examination Survey, those with higher vitamin D blood levels (≥80 nmol/L) had a 72 percent lower risk of colorectal cancer death than those with lower vitamin D blood levels (< 50 nmol/L) (14).
    Most colorectal cancers develop from pre-existing colorectal adenomas, and interventions that reduce the risk of adenoma development or recurrence are likely to reduce the risk of colorectal cancer. Several large studies have investigated the association of vitamin D intake or serum status with adenoma risk.
    A cohort from the National Cancer Institute (NCI)-sponsored Polyp Prevention Trial (PPT) was evaluated for the association of vitamin D intake with recurrence of colorectal adenomas in individuals who previously had one or more adenomas removed during a qualifying colonoscopy (15). PPT was a multicenter randomized clinical trial to determine the effects of a diet high in fiber, fruits, and vegetables and low in fat on adenoma recurrence. The detailed dietary information obtained during the trial allowed the researchers to investigate the association between additional dietary factors and adenoma recurrence. Total vitamin D intake (that is, from dietary sources and supplements combined) was not associated with a reduced risk of adenoma recurrence (15). However, individuals who used any amount of vitamin D supplements had a lower risk of adenoma recurrence (15).
    In another study, the vitamin D intakes of 3,000 people from several Veterans Affairs medical centers were examined to determine whether there was an association between intake and advanced colorectal neoplasia (an outcome that included high-risk adenomas as well as colon cancer) (16). Individuals with the highest vitamin D intakes (more than 16 μg, or 645 IU, per day) had a lower risk of developing advanced neoplasia than those with lower intakes (16).
    A pooled analysis of data from these and a number of other observational studies found that higher circulating levels of vitamin D and higher vitamin D intakes were associated with lower risks of colorectal adenoma (17). Inverse associations were seen with both dietary and total vitamin D intake but not with supplemental vitamin D intake. However, the associations with dietary intake were not statistically significant.
    Another large, NCI-sponsored randomized, placebo-controlled trial explored the effects of calcium supplementation and blood levels of vitamin D on adenoma recurrence (18). Calcium supplementation reduced the risk of adenoma recurrence only in individuals with vitamin D blood levels above 73 nmol/L. Among individuals with vitamin D levels at or below this level, calcium supplementation was not associated with a reduced risk (18).
  8. Is there evidence that vitamin D can help reduce breast cancer risk? Epidemiologic studies of the association between vitamin D and breast cancer risk have had conflicting results. Although several studies have suggested an inverse association between vitamin D intake and the risk of breast cancer, others have shown no association or even a positive association (that is, individuals with higher intakes had higher risks). A meta-analysis of six studies that investigated the relationship between vitamin D intake and breast cancer risk found no association (19). However, most women in these studies had relatively low vitamin D intakes, and, when the analysis was restricted to women with the highest vitamin D intakes (>10 μg, or 400 IU, per day), their breast cancer risks were lower than those of women with the lowest intakes (typically <1.25 μg, or 50 IU, per day) (19).
    In the Women’s Health Initiative, calcium plus vitamin D supplementation for an average of 7 years did not reduce the incidence of invasive breast cancer compared with placebo (20).

    The association between blood levels of vitamin D and breast cancer risk was examined in a cohort of postmenopausal women who were enrolled in NCI’s Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and from whom blood was drawn at study entry. During the subsequent follow-up period, 1,005 of these women developed breast cancer. When researchers compared the blood vitamin D levels of these women with those of 1,005 similar control women who did not develop breast cancer, they found no association between vitamin D status and risk of breast cancer (21).
  9. Is there evidence that vitamin D can help reduce prostate cancer risk? Some geographic correlation studies (see Question 6) have suggested that men exposed to higher levels of sunlight may have a lower risk of prostate cancer. Although some epidemiologic studies have suggested that men with higher vitamin D levels have an increased risk of prostate cancer, most studies have not shown such an association.
    In one relatively large study of men diagnosed 1 to 8 years after their blood was drawn, higher vitamin D blood levels were not associated with a lower risk of prostate cancer overall (22). Indeed, there was some evidence that men with higher vitamin D levels had an increased risk for aggressive disease (22).
    In another study, the European Prospective Investigation into Cancer and Nutrition (EPIC), blood samples obtained at study entry were examined for 652 men who developed prostate cancer during follow-up and 752 matched control subjects (23). No association was observed between serum vitamin D levels and risk of prostate cancer, either overall or by cancer stage.
  10. Is there evidence that vitamin D can help reduce pancreatic cancer risk? There is conflicting evidence about vitamin D’s relationship to risk of pancreatic cancer. A study of more than 120,000 men and women from the Health Professionals Follow-Up Study and the Nurses’ Health Study showed that participants with higher dietary intake of vitamin D had progressively lower risk of pancreatic cancer, compared with those who had the lowest intake (24). The estimates of vitamin D intake were based on detailed dietary information provided through questionnaires. Participants were followed for 16 years for the incidence of pancreatic cancer, and 365 cases were identified.
    In a study of men and women enrolled in the PLCO Screening Trial, no association between vitamin D level and pancreatic cancer risk was observed. The PLCO study examined vitamin D levels in blood from 184 individuals who were diagnosed with pancreatic cancer during nearly 12 years of follow-up and 368 matched cancer-free control subjects (25). In contrast, among Finnish male smokers participating in the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study (26), higher blood levels of vitamin D were associated with an increased risk of pancreatic cancer. More recently, in the NCI Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (see Question 11), men and women with the highest blood vitamin D levels (greater than 100 nmol/L, or 40 ng/mL) had twice the pancreatic cancer risk of men and women whose blood vitamin D levels were in the normal range of 50-75 nmol/L (20-30 ng/mL).
  11. Is there evidence that vitamin D can help reduce the risk of other rare cancers? A recent large collaborative effort analyzed data from 10 prospective cohort studies to examine whether vitamin D levels in blood were associated with seven rare cancers (27). The NCI Cohort Consortium Vitamin D Pooling Project of Rarer Cancers included information on blood vitamin D levels and incidence of rare cancers in a subset of more than 12,000 men and women. The researchers matched participants on date and season of blood draw and used other statistical techniques to adjust for seasonal variation in blood vitamin D levels. When the data from the different studies were pooled, there was no overall association between vitamin D level and risk of non-Hodgkin lymphoma or cancers of the endometrium, esophagus, stomach, kidney, or ovary. As described in Question 10, an increased risk of pancreatic cancer was observed in those with the highest blood levels of vitamin D (greater than 100 nmol/L or 40 ng/mL).
  12. What are the possible mechanisms by which vitamin D may modify cancer risk? Mechanisms by which vitamin D may modify cancer risk are not fully understood. Laboratory studies have shown that vitamin D promotes cellular differentiation, decreases cancer cell growth, and stimulates apoptosis (28, 29).
    Vitamin D acts on cells by binding to the vitamin D receptor (VDR). The VDR is a regulator of gene transcription that is found in the nucleus of cells. Vitamin D-bound VDR binds to the retinoid-X receptor (RXR), and the resulting complex activates the expression of specific genes. Among the many genes regulated by vitamin D are those that produce the proteins calbindin and TPRV6, both of which are involved in the absorption of calcium by intestinal cells (30). Another vitamin D-regulated gene is CYP3A4, whose protein product detoxifies the bile acid lithocholic acid (LCA). LCA is believed to damage the DNA of intestinal cells and may promote colon carcinogenesis. Stimulating the production of a detoxifying enzyme by vitamin D could explain a protective role for vitamin D against colon cancer (31).
    Further insight into the mechanisms by which vitamin D might modify cancer risk could come from study of the vitamin D receptor itself. A large number of variant forms of the VDR gene have been identified, some of which are known to alter the structure or function of the VDR protein. Some of these variants have been linked to risk for certain cancers, including prostate, colorectal, breast, bladder, and melanoma (32). The association of VDR variants with cancer risk differs by cancer site and appears to be modified by environmental exposures, such as diet and sun exposure.
  13. How can people get enough sunlight for vitamin D synthesis while minimizing the risk of skin cancer? Although people obtain some vitamin D from dietary sources, most vitamin D is made in the body after the skin is exposed to sunlight. Despite the known and potential health benefits of vitamin D, increasing sun exposure increases the risk of skin cancer. In general, most experts believe that people should continue to use sun protection when UV levels are moderate or higher. Some researchers have suggested that brief daily exposure to UV will ensure adequate vitamin D production, but many variables (such as skin color, latitude, and season) can affect the production of vitamin D, and such recommendations have proven controversial. Other experts recommend vitamin D supplementation to avoid the problem of increasing skin cancer risk.
  14. Does NCI recommend the use of vitamin D supplements to prevent colorectal or other cancers? NCI is a research institute and provides evidence-based results for others to interpret. Therefore, in general, NCI does not make recommendations on supplement use.
    Although some evidence suggests that vitamin D may provide some protection against colorectal and possibly other cancers, the evidence of potential benefit is limited and inconsistent. Moreover, some studies have suggested the possibility that higher vitamin D levels are associated with increased risk for some cancers, including pancreatic cancer.
Source:
http://www.cancer.gov/cancertopics/factsheet/prevention/vitamin-D
http://www.vitamindcouncil.org/cancerTreatment.shtml
http://www.nejm.org/doi/full/10.1056/NEJMp1102022?query=oncology-hematology
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Liya Kebede: Fighting for Maternal Health

According to Save the Children one in three women have no professional assistance during childbirth.

While the more fortunate are aided by traditional attendants many are alone during delivery putting them and their babies at grave risk.
In the age of modern medicine, why do so many mothers and newborns continue to go without proper care?

Source: http://english.aljazeera.net
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