Saturday, November 09, 2013

Best Vegetable to eat and worse vegetables to eat

By Dr. Mercola
There's little doubt that one of the best ways to improve your health is to make sure you're eating plenty of fresh, minimally processed high-quality vegetables, ideally locally-grown and organic, with a majority of them consumed raw (see my recommended list of vegetables below). One simple way to boost your vegetable intake is to juice them.
Juicing organic vegetables is highly recommended to patients in our clinic who are working to restore or improve their health. I am firmly convinced that juicing is one of the key factors to giving you a radiant, energetic life, and truly optimal health. I simply do not know of any other single nutritional intervention that has a more profound influence on health than eating and/or juicing fresh, organic vegetables.
You can review my comprehensive approach to how to juice on my vegetable juicing page. Even better, review my nutrition plan, which can help you take a comprehensive look at your overall health as it relates to food, and may even help you to change the way you think about eating.
Are All Vegetables the Same?
If you were to get all of your vegetables from conventionally farmed sources, this would be better for your health than eating no fresh vegetables at all. However, conventionally farmed vegetables are not your best choice. Organic vegetables are a much better option.
USDA Organic farmers (and many small, local organic farms working without certification) must use different standards when growing vegetables. These standards include never using:
The Environmental Protection Agency (EPA) considers 60 percent of herbicides, 90 percent of fungicides, and 30 percent of insecticides to be carcinogenic, and most are damaging to your nervous system as well. In fact, these powerful and dangerous chemicals have been linked to numerous health problems such as:
Disruption of your endocrine system
Immune system suppression
Male infertility and reduced reproductive function

This information alone should give you pause when considering whether to buy local, organic vegetables or not. But I encourage you to do further research about organic versus conventional farming conditions. I believe that after researching the facts and statistics, you'll come to the conclusion that organic vegetables are far more nutritious than conventionally farmed vegetables.
Conventional Fruit and Vegetable Pesticide Loads
Certainly helpful to your decision about which vegetables should be purchased organic and which conventional veggies may be safe, is the measured pesticide loads found on conventionally farmed fruits and vegetables. So if you need to work within a certain budget, use this information to help guide you to the best choices when it comes to lowering your overall pesticide exposure.
Of the 43 different fruit and vegetable categories tested by the Environmental Working Group and included in their Shoppers' Guide to Pesticides in Produce, the following 12 fruits and vegetables had the highest pesticide load, making them the most important to buy or grow organically:
Sweet bell peppers
Grapes (imported)

In contrast, the following foods were found to have the lowest residual pesticide load, making them the safest bet among conventionally grown vegetables:
Sweet peas (frozen)
Sweet corn (frozen)

The Importance of Fresh Vegetables
Buying your vegetables from a local organic source is the ideal way to ensure that your vegetables are both fresh and high-quality. I strongly advise you to avoid wilted vegetables of any kind, because when vegetables wilt, they lose much of their nutritional value. In fact, wilted organic vegetables may actually be less healthful than fresh conventionally farmed vegetables!
Another reason to buy your organic vegetables from a local source is that fresher vegetables also contain the highest amounts of biophotons.
What are the Biophotons?
Biophotons are the smallest physical units of light, which are stored in and used by all biological organisms – including your body. Dr. Fritz-Albert Popp was the first to suggest that this light inside all biological organisms must originate, at least in part, from the foods you eat. When you eat plant foods, the light waves (photons) are thought assimilate into the cells in your body. The purpose of these biophotons is much more important than many have realized, because they are the transmitters of important nutritional bio-information used in many complex vital processes in your body.
Every living organism emits biophotons, or low-level luminescence (light with a wavelength between 200 and 800 nanometers). It is thought that the higher the level of light energy a cell emits, the greater the vitality and potential for the transfer of light energy to your body. In other words, the more light a food is able to store, the more nutritious it is when you consume it. Fresh, organic vegetables are naturally rich in this biophoton light energy.
Illness Can Occur When Biophoton Emissions are Out of Sync
Research by Dr. Popp also showed that the light emissions of healthy people follow a set of biological rhythms by day and night, and also by week and month. However, in his studies, the light emissions from cancer patients had no such rhythms and appeared scrambled, which suggests that their cells were no longer communicating properly. Likewise, according to Dr. Popp's research, multiple sclerosis patients were taking in too much light, leading to what he considered confusion on a cellular level.
Even stress can influence your biophoton emissions, causing them to increase when stress increases. It's also known that cancer-causing chemicals alter your body's biophoton emissions, interrupting proper cellular communication, while certain natural substances can help to restore proper cellular communication.
For instance, Dr. Popp found that mistletoe appeared to restore biophoton emissions of tumor cells to a normal level! Interestingly, even conventional medicine confirmed that mistletoe extract does appear to have a beneficial effect on cancer1, with one study2 published in Alternative Therapies in Health and Medicine showing that mean survival rates nearly doubled among breast cancer patients who received mistletoe extract.
An Important Tip for Gathering Valuable Light Energy
As regular readers know, I've long recommended eating a diet of mostly RAW food to stay optimally healthy. This is because living raw foods have the highest biophoton energy. The greater your store of light energy from healthy raw foods (this should not be confused with your vitamin D status, which is produced by the sun on your skin), the greater the power of your overall electromagnetic field, and consequently the more energy is available for healing and maintenance of optimal health.
I firmly believe it's only a matter of time before the importance of light energy in your health and well-being becomes more widely recognized and applied in the field of medicine. Until then, remember that your body is not only made up of tissue, blood vessels, and organs—it's also composed of light.
Reasons to Juice
As I mentioned at the beginning, one of the best ways to get ample amounts of raw vegetables into your diet is through juicing. Many people see juicing as inconvenient, but with the proper juicer, it's really not very time consuming at all. The fact is, many people initially think juicing will be a real chore, but most are pleasantly surprised to find it's much easier than they thought. There are three main reasons why you will want to consider incorporating organic vegetable juicing into your optimal health program:
  • Juicing helps you absorb most of the nutrients from the vegetables. This is important because most of us have impaired digestion as a result of making less-than-optimal food choices over many years. This limits your body's ability to absorb all the nutrients from the vegetables. Juicing will help to "pre-digest" them for you, so you will receive most of the nutrition, rather than having it go down the toilet.
  • Juicing allows you to consume an optimal amount of vegetables in an efficient manner. If you are a carb type, you should eat one pound of raw vegetables per 50 pounds of body weight per day. Some people may find eating that many vegetables difficult, but it can be easily accomplished with a quick glass of vegetable juice.
  • You can add a wider variety of vegetables in your diet. Many people eat the same vegetable salads every day. This violates the principle of regular food rotation and increases your chance of developing an allergy to a certain food. But with juicing, you can juice a wide variety of vegetables that you may not normally enjoy eating whole.
Start by juicing only vegetables that you enjoy eating non-juiced. The juice should taste pleasant -- not make you feel nauseous. It is very important to listen to your body when juicing. Your stomach should feel good all morning long. If it is churning or growling or generally making its presence known, you probably juiced something you should not be eating. Personally, I've noticed that I can't juice large amounts of cabbage, but if I spread it out, I do fine.
Please review my comprehensive vegetable juicing instructions for more information. To learn more about the ins-and-outs of juicing, you can also check out my three-part interview with Cherie Calbom, aka "The Juice Lady":

What are the Best Vegetables for Good Health?
My Recommended List of Vegetables provides a guide to the most nutritious vegetables, and those to limit due to their high carbohydrate content. Remember: the greener the vegetable, the more nutritious it will be. Ideally, you'll want to juice vegetables that are appropriate for your particular nutritional type, which I'll summarize below. There is a basic test you can take to find out your nutritional type, which is detailed in my book, Take Control of Your Health. Alternatively, you can take the free online Nutritional Typing test.
As a general guide, the following list of vegetables details some of the best and worst vegetables for your health.
Highly Recommended Vegetables
Avocado (actually a fruit)
Beet greens
Green and red cabbage
Bok Choy
Brussels sprouts
Lettuce: romaine, red leaf, green leaf
Mustard greens
Chinese cabbage
Peppers: red, green, yellow and hot
Collard greens
Dandelion greens

Use sparingly due to high carbohydrate levels
Winter Squashes

Vegetables to Avoid

Tips to Make Your Juice Taste Better
If you would like to make your juice taste a bit more palatable, especially in the beginning, you can add these elements:
  • Coconut: This is one of my favorites! You can purchase the whole coconut or use unsweetened shredded coconut. It adds a delightful flavor and is an excellent source of fat to balance your meal. Coconut has medium chain triglycerides, which have many health benefits. You can even add coconut water to your juice, which is an excellent natural source of electrolytes, especially potassium.
  • Lemons and Limes: You can add half a lemon or lime (leaving much of the white rind on), which really brightens up the flavor of your juice.
  • Cranberries: Researchers have discovered that cranberries have five times the antioxidant content of broccoli, which means they may help protect against cancer, stroke and heart disease. Limit the cranberries to about 4 ounces per pint of juice.
  • Fresh ginger: This is an excellent addition if you can tolerate it. It gives your juice a little "kick"! And, as an added boon, researchers have found ginger can have dramatic benefits for cardiovascular health, including preventing atherosclerosis, lowering cholesterol levels, and preventing the oxidation of low-density lipoprotein (LDL).
Nutritional Typing and Juicing Vegetables
According to Nutritional Typing principles, if you are a carb type, vegetable juicing is STRONGLY recommended. With patients in our clinic, we strongly encourage carbohydrate types to juice if they expect to regain their health. If you are a mixed type, it is certainly useful to juice. However, protein types need to follow some specific guidelines to make it work for them, which I'll review below.
Do you know your nutritional type? If not, you can easily determine this by taking my free online nutritional type test.
Protein Types and Juicing Vegetables
If you are a protein type, juicing needs to be done cautiously. The only vegetables you should juice are your prime protein type vegetables, which are celery, spinach, asparagus, string beans and cauliflower (including the base).
Also, to make drinking vegetable juice compatible with protein type metabolism (which needs high amounts of fat), it is important to blend a source of raw fat into the juice. Raw cream, raw butter, raw eggs, avocado, coconut butter, or freshly ground flax seed are the sources of raw fat I most recommend. In addition to adding a source of raw fat to your juice, you may also find that adding some, or even all, of the vegetable pulp back into your juice helps make it more satisfying
Final Thoughts about Vegetables
The truth is, scientists really don't know all that much about nutrients, and taking isolated nutrients through supplements is not always a good idea. A much better way to get the vital nutrients your body needs is through eating whole, fresh organic vegetables. I recommend at least one third of your total diet be eaten raw, and a great way to do this is through incorporating juicing into your eating plan. Personally, I aim for consuming about 80 percent of my food raw, including raw eggs, dairy, and meat.

I want to emphasize that eating any vegetable is better than eating no vegetables at all, so don't get down on yourself if you're able to juice organic fresh vegetables only a few times a week. Even if you have to start slowly, I think you'll soon begin to notice positive changes to your health when you increase your fresh vegetable intake. Also, please review my complete nutrition plan, which can help you take a comprehensive look at your health as it relates to food, and may even help you change the way you think about eating.

Eat Your Broccoli

November 09, 2013 | 19,398 views

By Dr. Mercola
Vegetables have an impressive way of offering widespread benefits to your health, and broccoli is no exception. When you eat broccoli you’re getting dozens, maybe even hundreds, of super-nutrients that support optimal, body-wide health.
Man-made substances just can’t compare, and that’s why, if you take just one piece of advice away from your childhood, make it this one: eat your broccoli!
5 Leading Benefits of Broccoli
We’ve compiled an extensive review of the health benefits of broccoli on our Broccoli Food Facts page. This cruciferous veggie (in the same family as Brussels sprouts, cabbage, cauliflower, and more) is one of the best health-boosting foods around, with research proving its effectiveness for …
1. Arthritis
Recent tests on cells, tissues and mice show that a sulfur-rich broccoli compound, sulforaphane, blocks a key destructive enzyme that damages cartilage.1 It’s thought that increasing broccoli in your diet may help to slow down and even prevent osteoarthritis.
2. Cancer
Sulforaphane in broccoli has also been shown to kill cancer stem cells, thereby striking to the root of tumor growth, and the broccoli compound glucoraphanin -- a precursor to sulforaphane – boosts cell enzymes that protect against molecular damage from cancer-causing chemicals.2, 3
Studies have also found that sulforaphane normalizes DNA methylation4 —a process that involves a methyl group (one carbon atom attached to three hydrogen atoms) being added to part of a DNA molecule, and therefore influencing its expression.
DNA methylation is a crucial part of normal cell function, allowing cells to "remember who they are and where they have been" and is indispensable for regulating gene expression.
DNA methylation also suppresses the genes for things you don’t want, such as viral and other disease-related genes, and abnormal DNA methylation plays a critical role in the development of nearly all types of cancer.
One study published in PLoS One,5 for instance, found that just four servings of broccoli per week could protect men from prostate cancer. One serving of broccoli is about two spears, so that's only 10 broccoli spears per week.
In this study, the researchers collected tissue samples over the course of the study and found that the men who ate broccoli showed hundreds of beneficial changes in genes known to play a role in fighting cancer.
3. Blood Pressure and Kidney Health
Sulforaphane in broccoli may also significantly improve your blood pressure and kidney function, according to yet another study in which hypertensive rats with impaired kidney function were given sulforaphane. The natural compound improved the rats' kidney function and lowered their blood pressure by normalizing DNA methylation patterns within their cells.6
4. Anti-Aging and Immune System Health
Sulforaphane also seems to stimulate a variety of antioxidant defense pathways in your body that can directly reduce oxidative stress and slow down the decline in your immune system that happens with age.7 In theory, this means that eating vegetables that contain sulforaphane, such as broccoli, could quite literally slow down the hands of time.
5. Heart Health, Especially for Diabetics
Sulforaphane encourages production of enzymes that protect the blood vessels, and reduces the number of molecules that cause cell damage -- known as Reactive Oxygen Species (ROS) -- by up to 73 percent.8 People with diabetes are up to five times more likely to develop cardiovascular diseases such as heart attacks and strokes -- both of which are linked to damaged blood vessels. Eating broccoli may help to reverse some of this damage.
Broccoli Benefits Your Eyes, Your Skin and Much More
The benefits of broccoli are seemingly endless. It’s also known, for instance, that broccoli:9
Supports your body’s detoxification, thanks to the phytonutrients glucoraphanin, gluconasturtiian, and glucobrassicin
Is anti-inflammatory (inflammation is at the root of many chronic diseases)
Contains the flavonoid kaempferol, which may fight allergies and inflammation
Contains significant amounts of fiber to facilitate better digestion
Supports eye health, thanks to high levels of the carotenoids lutein and zeaxanthin
Benefits your skin, as sulforaphane helps repair skin damage
Is rich in beneficial nutrients like potassium, calcium, protein and vitamin C
May reduce blood sugar levels, as it contains both soluble fiber and chromium
Supports heart health and contains lutein, which may help prevent thickening of your arteries
The ‘Secret’ Way to Enhance the Health Benefits of Broccoli
I call it secret because so many people believe that the only way to eat broccoli is after it’s been roasted or steamed. Not so, as broccoli can also be enjoyed raw or even ‘tender-crisp’ – which is one of the best ways to protect its nutrient levels. However, an even better way to get the health benefits of broccoli is by eating its sprouts. Fresh broccoli sprouts are FAR more potent nutritionally speaking than mature broccoli, allowing you to eat far less in terms of quantity to get key therapeutic compounds like sulforaphane.
This is also an excellent alternative if you don’t like the taste (or smell) of broccoli. In terms of research, even small quantities of broccoli sprout extracts have been shown to markedly reduce the size of rat mammary tumors that were induced by chemical carcinogens. According to researchers at Johns Hopkins University:10
"Three-day-old broccoli sprouts consistently contain 20 to 50 times the amount of chemoprotective compounds found in mature broccoli heads, and may offer a simple, dietary means of chemically reducing cancer risk.”
When compared to either broccoli or cauliflower, which also contains sulforaphane,11 three-day-old broccoli sprouts contain anywhere from 10 to 100 times higher levels of glucoraphanin, compared to the mature varieties. Best of all, you can grow broccoli sprouts at home quite easily and inexpensively. Another major benefit is that you don't have to cook them. They are eaten raw, usually as an addition to salad, making them a super-healthy convenience food!
How to Grow Your Own Broccoli Sprouts
Broccoli sprouts look and taste similar to alfalfa sprouts, and are easily grown at home, even if you’re limited on space. I strongly recommend using organic seeds, and a pound of seeds will probably make over 10 pounds of sprouts. From the researcher’s calculations mentioned earlier, this can translate to as much cancer-protecting phytochemicals as 1,000 pounds (half a ton) of broccoli!
I used to grow sprouts in Ball jars over 10 years ago but stopped doing that. I am strongly convinced that actually growing them in soil is far easier and produces more nutritious and abundant food. It is also less time consuming, as with Ball jars you need to rinse them several times a day to prevent mold growth. Trays also take up less space than jars. I am now consuming one whole tray of sprouts every 2-3 days, and to produce that much food with Ball jars I would need dozens of jars. I simply don't have the time or patience for that. You can find instructions on how to grow sprouts by viewing a step-by-step guide at
Broccoli is Only One “Superstar” Veggie
There’s no doubt that broccoli is a vegetable you should strive to eat frequently, but like most foods if you eat it too often you may grow tired of it or even develop an aversion to it.  Fortunately you don’t have to because there are so many vegetables to choose from that you can’t possibly get tired of them..
My best recommendation is to eat a variety of vegetables each day. My Recommended Vegetables List provides a guide to the most nutritious vegetables and those to limit due to their high carbohydrate content. You can also get creative with how you consume them, alternating whole vegetables with freshly prepared vegetable juice and fermented vegetables.
As an example, you can easily consume several different types of raw vegetables each day just by thinking outside the box for your lunchtime salad. My current salad consists of about half a pound of sunflower sprouts, four ounces of fermented vegetables, half a large red pepper, several tablespoon of raw organic butter, some red onion, a whole avocado and about three ounces of salmon or chicken.

You could also add some raw broccoli or broccoli sprouts, asparagus, garlic, tomatoes, celery, parsley, spinach, zucchini and so on. The key is to branch out beyond plain lettuce. Of course, you can also get creative with your recipes. The New York Times12 recently featured several broccoli recipes that sound delicious, including broccoli, quinoa and purslane salad, broccoli stem and red pepper slaw and roasted broccoli with tahini garlic sauce. If you’re bored with broccoli, give these recipes a try (and do share how they taste by commenting below!).

Tuesday, September 24, 2013

Effects of age on male fertility.

Best Pract Res Clin Endocrinol Metab. 2013 Aug;27(4):617-28. doi: 10.1016/j.beem.2013.07.004. Epub 2013 Aug 17.
Effects of age on male fertility.
Centre for Reproductive Medicine and Andrology/Clinical Andrology, Domagkstrasse 11, D-48149 Muenster, Germany. Electronic address:
Later parenting is considered by many to have advantages, parents-to-be may feel themselves more stable to rear children. In addition, many men start a second family later in life. Thus, paternal age becomes an emerging issue. Aging affects male fertility by a scope of factors, which are not fully understood to date. Generally, the amount of produced sperm cells as well as their motility decreases with age, as testicular histological architecture deteriorates. Decreased fecundity and an increased risk for disturbed pregnancies occur with advancing paternal age. Some rare autosomal dominant pathologies are clearly related to paternal age. Altered patterns of epigenetics/gene expression in aging sperm seem to affect a range of neurocognitive disorders and also metabolic dyshomeostasis across generations. Such effects refer to men older than 40 years and may have impact on socio-economic issues. Nevertheless, councelling of older men seeking paternity should be patient-oriented and weigh statistical probabilities against the right for individual life-planning.
Copyright © 2013 Elsevier Ltd. All rights reserved.

aging and sperm, aging fathers, epigenetics and fertility, male fertility, paternal age

Friday, June 07, 2013

New evidence for positive selection helps explain the paternal age effect observed in achondroplasia.

Hum Mol Genet. 2013 Jun 4. [Epub ahead of print]
New evidence for positive selection helps explain the paternal age effect observed in achondroplasia.
Molecular and Computational Biology Program, University of Southern California, Los Angeles 90089, California, United States of America.
There are certain de novo germline mutations associated with genetic disorders whose mutation rates per generation are orders of magnitude higher than the genome average. Moreover, these mutations occur exclusively in the male germ line and older men have a higher probability of having an affected child than younger ones, known as the paternal age-effect. The classic example of a genetic disorder exhibiting a PAE is achondroplasia, caused predominantly by a single nucleotide substitution (c.1138G>A) in FGFR3. To elucidate what mechanisms might be driving the high frequency of this mutation in the male germline, we examined the spatial distribution of the c.1138G>A substitution in a testis from an 80-year old unaffected man. Using a technology based on bead-emulsion amplification, we were able to measure mutation frequencies in 192 individual pieces of the dissected testis with a false positive rate lower than 2.7x10-6. We observed that most mutations are clustered in a few pieces with 95% of all mutations occurring in 27% of the total testis. Using computational simulations, we rejected the model proposing an elevated mutation rate per cell division at this nucleotide site. Instead we determined that the observed mutation distribution fits a germline selection model, where mutant spermatogonial stem cells have a proliferative advantage over unmutated cells. Combined with data on several other PAE mutations, our results support the idea that the PAE, associated with a number of Mendelian disorders, may be explained primarily by a selective mechanism.

PMID: 23740942 [PubMed - as supplied by publisher]

Thursday, June 06, 2013

Common Genetic Disease Linked to Father’s Age

Common Genetic Disease Linked to Father’s Age
1 hour ago

Genetic mutation of a testis stem cell actually gives the disease an edge, making older fathers more likely to pass it along to their children
Scientists at USC have unlocked the mystery of why new cases of the genetic disease Noonan Syndrome are so common: a mutation that causes the disease disproportionately increases a normal father’s production of sperm carrying the disease trait. 
When this Noonan syndrome mutation arises in a normal sperm stem cell it makes that cell more likely to reproduce itself than stem cells lacking the mutation. The father then is more likely to have an affected child because more mutant stem cells result in more mutant sperm. The longer the man waits to have children the greater the chance of having a child with Noonan syndrome.
Noonan Syndrome is among the most common genetic diseases with a simple inheritance pattern. About one of every 4,000 live births is a child with a new disease mutation. The disease can cause craniofacial abnormalities, short stature, heart defects, intellectual disability and sometimes blood cancers.
By examining the testes from 15 unaffected men, a team led by USC molecular and computational biologists Norman Arnheim and Peter Calabrese found that the new mutations were highly clustered in the testis, and that the overall proportion of mutated stem cells increased with age. Their computational analysis indicated that the mutation gave a selective edge over non-mutated cells.
“There is competition between stem cells with and without the mutation in each individual testis,” said Arnheim, who has joint appointments at the USC Dornsife College of Letters, Arts and Sciences and the Keck School of Medicine of USC. “But what is also unusual in this case is that the mutation which confers the advantage to testis stem cells is disadvantageous to any offspring that inherits it.”
The new findings also suggest an important new molecular mechanism to explain how certain genetic disease mutations can alter sperm stem cell function leading to exceptionally high frequencies of new cases every generation.
The Arnheim and Calabrese team included USC postdoctoral research associates Song-Ro Yoon, and Soo-Kung Choi, graduate student Jordan Eboreime and Dr. Bruce D. Gelb of the Icahn School of Medicine at Mount Sinai in New York City. A paper detailing their research will be published on June 6 in The American Journal of Human Genetics.
This research was supported by the National Institute of General Medical Sciences grant number R01GM36745 and the National Heart, Lung and Blood Institute (National Institutes of Health) grant number HL071207.

Contact: Robert Perkins at (213) 740-9226 or

Tuesday, May 21, 2013

. Recent studies have shown that 76% of new mutations originate in the paternal lineage and provide unequivocal evidence for an increase in mutation with paternal age.

Trends Genet. 2013 May 16. pii: S0168-9525(13)00070-X. doi: 10.1016/j.tig.2013.04.005. [Epub ahead of print]
Properties and rates of germline mutations in humans.
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
All genetic variation arises via new mutations; therefore, determining the rate and biases for different classes of mutation is essential for understanding the genetics of human disease and evolution. Decades of mutation rate analyses have focused on a relatively small number of loci because of technical limitations. However, advances in sequencing technology have allowed for empirical assessments of genome-wide rates of mutation. Recent studies have shown that 76% of new mutations originate in the paternal lineage and provide unequivocal evidence for an increase in mutation with paternal age. Although most analyses have focused on single nucleotide variants (SNVs), studies have begun to provide insight into the mutation rate for other classes of variation, including copy number variants (CNVs), microsatellites, and mobile element insertions (MEIs). Here, we review the genome-wide analyses for the mutation rate of several types of variants and suggest areas for future research.
Copyright © 2013 Elsevier Ltd. All rights reserved.
PMID: 23684843 [PubMed - as supplied by publisher]

Saturday, March 16, 2013

Impact of age on male fertility.

2013 Mar 13. [Epub ahead of print]

Impact of age on male fertility.


University of Tennessee Graduate School of Medicine, Knoxville, Tennessee, USA.



An increasing number of older men are seeking help for fathering a child, but male fertility gradually declines with age. This review highlights changes in male reproductive biology and practical clinical concerns for aging men.


Aging may have an impact on sperm DNA damage such as single nucleotide polymorphisms. A recent landmark study identified that the number of single gene de-novo mutations in the offspring increased by two mutations per year based on paternal age. Additionally, advanced paternal age has been linked with neurocognitive disorders such as autism and schizophrenia. For the management of hypogonadism, strategies using selective estrogen modulators have been increasingly utilized to maintain fertility potential.


Aging has an impact on male fertility potential, as well as potential genetic effects for the offspring.

Tuesday, September 11, 2012

Paternal Age and Risk of Autism in an Ethnically Diverse, Non-Industrialized Setting: Aruba

Paternal Age and Risk of Autism in an Ethnically Diverse, Non-Industrialized Setting: Aruba

ObjectiveThe aim of this study was to examine paternal age in relation to risk of autism spectrum disorders (ASDs) in a setting other than the industrialized west.DesignA case-control study of Aruban-born children (1990–2003). Cases (N = 95) were identified at the Child and Adolescent Psychiatry Clinic, the only such clinic in Aruba; gender and age matched controls (N = 347) were gathered from public health records. Parental age was defined categorically (≤29, 30–39, 40–49, ≥50y). The analysis was made, using conditional logistic regression.ResultsAdvanced paternal age was associated with increased risk of ASDs in offspring. In comparison to the youngest paternal age group (≤29y), risk of autism increased 2.18 times for children born from fathers in their thirties, 2.71 times for fathers in their forties, and 3.22 thereafter.ConclusionThis study, part of the first epidemiologic study of autism in the Caribbean, contributes additional evidence, from a distinctive sociocultural setting, of the risk of ASD associated with increased paternal age.
Ingrid D. C. van Balkom1,2,3*, Michaeline Bresnahan4,5, Pieter Jelle Vuijk6, Jan Hubert7, Ezra Susser4,5,8, Hans W. Hoek4,9,10
1 Child and Adolescent Psychiatry Clinic, Oranjestad, Aruba, 2 Jonx Department of Youth Mental Health, Lentis Psychiatric Institute, Groningen, The Netherlands, 3 Rob Giel Research Center, Department of Psychiatry, University Medical Center of Groningen, University of Groningen, Groningen, The Netherlands, 4 Mailman School of Public Health, Columbia University, New York, New York, United States of America, 5 New York State Psychiatric Institute, New York, New York, United States of America, 6 Department of Clinical Neuropsychology, VU University, Amsterdam, The Netherlands, 7 Child and Youth Health Services, Department of Public Health of Aruba, Oranjestad, Aruba, 8 College of Physicians and Surgeons of Columbia University, New York, New York, United States of America, 9 Parnassia Bavo Psychiatric Institute, The Hague, The Netherlands, 10 Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Abstract Top


The aim of this study was to examine paternal age in relation to risk of autism spectrum disorders (ASDs) in a setting other than the industrialized west.


A case-control study of Aruban-born children (1990–2003). Cases (N = 95) were identified at the Child and Adolescent Psychiatry Clinic, the only such clinic in Aruba; gender and age matched controls (N = 347) were gathered from public health records. Parental age was defined categorically (≤29, 30–39, 40–49, ≥50y). The analysis was made, using conditional logistic regression.


Advanced paternal age was associated with increased risk of ASDs in offspring. In comparison to the youngest paternal age group (≤29y), risk of autism increased 2.18 times for children born from fathers in their thirties, 2.71 times for fathers in their forties, and 3.22 thereafter.


This study, part of the first epidemiologic study of autism in the Caribbean, contributes additional evidence, from a distinctive sociocultural setting, of the risk of ASD associated with increased paternal age.

Introduction Top

Major studies showing that advanced paternal age elevates risk of autism in offspring have been conducted in predominantly high-income countries (the United States (California), Denmark, Israel, Western Australia, Sweden, the Netherlands, the United Kingdom) [1][6].
The mechanisms underlying the association between advanced parental age and autism risk are not yet fully understood. The leading hypothesis is that with advancing paternal age, de novo genomic alterations and/or changes in gene expression regulation levels increase the risk of autism [7], [8]. Alternatively, delayed parenthood could reflect sub threshold autistic traits in individuals leading them to delay parenting [9], [10]. There are also suggestions that sociocultural determinants of age at parenting may better explain the finding. Sociocultural factors which influence age at parenting differ across countries and include factors such as immigration, access to family planning services, educational attainment, and socioeconomic status [11][14]. The significance of these sociocultural factors is difficult to evaluate due to the lack of sociocultural diversity of the major studies to date. Studies of autism in a greater diversity of settings are underway or have recently been published [15], [16]. Among the first of these was a prevalence study of treated autism spectrum disorders in Aruba [17]. Our aim in the current study was to examine the hypothesis that advanced paternal age increases risk of autism in the non-industrial, ethnically diverse setting of Aruba.

Methods Top

Area and population

Aruba is a Caribbean island 17 miles off the coast of Venezuela (population 90,506 in 2000) The native-born population of Aruba is predominantly of Amerindian (Arawak), Dutch, and Spanish ancestry [18]. In conjunction with an economic transition in the 1990s, Aruba absorbed a large number of immigrants. Since 2000, immigrants have constituted at least 30% of the population [19]. Although social distinctions based on race may exist, these are nowhere documented, and race is officially considered a continuously distributed trait. During the 1990s health insurance was nearly universal for legal residents; in 2001 access to health care in Aruba improved further with the introduction of mandatory health insurance. All children of legal residents are entitled to health care [17].

Study Design

This study is a population-based case-control study using clinic and public health records. The sampling frame includes all births in Aruba between 1990 and 2003 recorded in the Aruban public health records. Autism in children born between 1990–1999 had previously been identified in the Aruba Autism Project, a prevalence study of Autism Spectrum Disorders (ASDs) in Aruba [17]. This earlier prevalence study was extended to include children born from 1990 to 2003, from clinic records of assessments recorded until January 1, 2006. Controls were selected from the public health records (well-baby clinics records and adolescent health preventative clinic records) matching on date/month/year of birth and gender.

Case identification

Records from the Aruba Child and Adolescent Psychiatry Clinic, the first and only child and adolescent psychiatry service on the island, were systematically screened for diagnosed and suspected cases of ASD in children born in Aruba from 1990 to 2003, extending the birth years investigated in the prevalence study of treated ASDs in Aruba [17]. Standardized chart abstractions were conducted on all potential cases, including children with a clinic ASD diagnosis, or a working diagnosis [20] of ASD; abstracts were reviewed and a study diagnosis was assigned based on chart evidence of symptoms in accordance with DSM-IV symptom criteria. Autism Spectrum Disorders were defined to include Autistic Disorder, Asperger's Disorder, and Pervasive Developmental Disorder Not Otherwise Specified. Eligibility for inclusion in the analysis was based wholly on chart review, and not on standing clinic diagnosis. In total, 101 cases of ASDs were identified by these methods and included; 23 of these cases were validated in a previous study (see Van Balkom et al., 2009 [17] for a more complete description).

Control identification

A minimum of three and a maximum of five controls, matched to each subject classified with an ASD for date of birth and gender, were randomly selected from the public health records. With these methods 469 controls were identified for the 101 ASD subjects.

Covariate information

Data on controls were abstracted from the centralized computer records of the Aruban public health clinics, which serve all Aruban children from infancy to age 10 to 11 years. Public health clinic files for selected controls were retained in one of two locations (the centralized archive or home clinic) depending upon birth years. Clinic files include immunization history, visit notes, and in most instances parental characteristics including parents' place of birth, date and/or year of birth, maternal parity, and parental occupation. Parental characteristics were abstracted for each control using a standardized abstraction form. Only anonymized data were extracted from the clinic records. A similar abstraction process for parental characteristics of cases was carried out.
Characteristics of the study sample are shown in Table 1.
thumbnailTable 1. Characteristics of the study sample.
Six of the cases classified as ASD for this study were excluded due to missing data on mother and/or father's age along with their 26 matched controls. An additional 96 controls were excluded due to missing data on maternal and/or paternal age. The final sample consisted of 95 cases and 347 controls.


Paternal and maternal age, the primary confounder [6], [21], were defined as categorical variables. Parental age was categorized in 10 year increments, resulting in four categories of paternal age (≤29 = age group 1 (reference category), 30–39 = age group 2, 40–49 = age group 3, and ≥50 = age group 4), and three categories of maternal age as there were no mothers older than 49 years (≤29 = age group 1 (reference category), 30–39 = age group 2, and 40–49 = age group 3). Three additional covariates were identified for inclusion as possible confounders: low birth weight [13], [23], [24], preterm birth [13], [22][24] and parental immigrant status [4], [25]. Low birth weight was defined as <2 11="11" 39="39" and="and" aruba="aruba" as="as" birth="birth" class="inline-formula" classified="classified" grams="grams" not="not" of="of" parental="parental" place="place" pregnancy="pregnancy" preterm="preterm" span="span" was="was" weeks="weeks">
); from this four categories of combined parental place of birth were defined, i.e. AFAAMO (reference category, N = 207), AFAMO (N = 90), FAAMO (N = 47), FAMO (N = 74); for 24 children the birthplace of the parents was unknown. Neither low birth weight, nor parental immigrant status were associated with ASD in bivariate analysis, and were therefore dropped from the models.


The data were analyzed using STATA version 9. Conditional logistic regression was used for matched case-control groups with STATA's “clogit” command to examine paternal age effects of increased risk in ASDs in offspring unadjusted, while controlling for maternal age effects, and while controlling for maternal age and preterm birth effects, as well as the interaction effect beteen maternal age and paternal age.


In keeping with Dutch medical ethical guidelines for the conduct of record review studies personal information was treated confidentially. Only the treating child psychiatrist and the research psychiatrist had access to the medical charts. Data were entered into a statistical database without identifying information. Informed consent was not applicable. The study was approved by the Ministry of Health of Aruba.

Results Top

Mean paternal age in cases was 33.5 (sd = 6.8), and in controls 31.1 (sd = 7.1) years; mean maternal age in cases was 30.2 (sd = 5.7), and in controls 27.6 (sd = 5.6) years.
Advanced paternal age was associated with increased risk of ASDs in offspring (Table 2). In comparison to the youngest paternal age group (≤29), the risk of autism increased significantly to 2.18 times (p = .004) for children with fathers in their thirties, and to 2.71 times (p = .01) in their forties. Adjusting for maternal age, paternal age effects were significant for fathers in their thirties, compared to younger fathers. However effects were rendered non-significant for other paternal age groups. When adjusting for confounding variables maternal age and preterm birth, fathers in their thirties (OR = 2.16; p = .02) and forties (OR = 2.67; p = .04) have a significantly increased risk for ASDs in their offspring compared to the reference group. No significant interaction effect was found between paternal age and maternal age (p = .55).
thumbnailTable 2. Odds ratios for paternal age adjusted for maternal age and preterm birth.

Discussion Top

In this case-control study in a total population Aruban birth cohort (1990–2003) we found that advanced paternal age, in comparison to young paternal age (≤29), was associated with a greater than two-fold increased risk of ASDs in offspring. Adjusting for both maternal age and preterm birth had little impact on the finding. These results are consistent with other reports from western countries [1][6], and fall within the range of effects reported in a recent meta-analysis [4].
The leading explanations for increasing risk with advancing paternal age are genetic mutations/cytogenetic abnormalities known to increase with age [26], [27], or age associated methylation differences [28]. The leading alternative explanation is that subthreshold autistic traits in the fathers, associated with delayed or late parenting, elevates the risk of autism. Support for this hypothesis is based in part on evidence of social and communication impairments in parents and siblings of autistic probands, referred to as the broader autism phenotype (BAP) [29].
Attempts to discriminate between the two major alternatives (mutation/epigenetics versus broader autism phenotype self selection) have adopted different strategies. The first strategy is the most direct, and examines parental characteristics and reproductive age in multiplex families. Using this strategy, Puleo and colleagues [10] found that no major dimension of the broader autism phenotype increased with age at paternity.
A second strategy, also focused within affected families, reasons that an association of paternal age and risk of autism within affected families argues against a primary role for the self-selection hypothesis. Hultman et al. [4] examined paternal age effects in sibships with one or more autistic children, and one non-autistic sibling, and found that the association was observed in first born and subsequent births. Stratifying on age at birth of first child, increasing risk with advancing paternal age was reported for all but one strata. Parner et al. [30] included a sibling subcohort analysis which adjusted for common genetic and environmental factors, and found that the parental age association persisted, and increased risk of ASD could not be explained by these factors.
The study in Aruba reflects a third strategy. This approach, focused on culturally distinct environments, reasons that in different cultural circumstances individuals selected into delayed parenting will differ. For example, it is likely that social, cultural, and ethnic influences on age of reproduction in Aruba are affected by the transitional economy and the rapid influx of immigrants, changing the meaning of older ages at parenting. If paternal age effects are consistent across cultures, this would argue for an age related, rather than BAP related effects.
In Aruba, we found a two to three-fold increased risk of autism in offspring associated with advancing paternal age. These findings add to the line of evidence demonstrating consistent paternal age effect in culturally dissimilar environments. Two case control studies in non-western countries – Iran and China – have recently been published [15], [16]. In the Iranian study, controls were matched to cases on parental education, birth order, sex, consanguinity, urbanism and province. In matched analysis, fathers age 35–39 had nearly a twofold increased risk, and fathers 40+ a 2.58 times increased risk compared to fathers aged 25–29. A small case control study in Tianjin, China, reported a significant advanced paternal age (>30) effect, associated with increased risk of 2.63 adjusting for sex and birth year. Maternal age effects were nonsignificant. It is notable that in both Iran and China, arranged marriages are common.

Strengths and limitations

Major strengths of the study include access to rigorously defined cases arising in the total population of Aruban births 1990–2003, ascertainment through the only child psychiatry clinic within a well-established universal health care system, and accurate enumeration of the population at risk through the population registry.
Nonetheless, the limitations of the present study also need to be considered. First, the small sample size is an inherent limitation to the study of this population. In addition, the decrease in the effect size for paternal age when maternal age is added to the model, may reflect the difficulty of fully separating paternal and maternal age effects; the instability of the confidence intervals clearly reflects the limited sample size.
A second limitation pertains to the record-based methodology. Findings with respect to assigning a study diagnosis, as in any record-based study, are usually limited by the absence of in-person standardized research interviews and direct clinical assessments of the study classified cases. However, in a prior validation study (N = 30; 24 cases and 6 controls) we reported that 23 of the 24 cases were confirmed. Since these 23 cases have been included in the present study the diagnosis of 24% of present study cases was validated [17].

Conclusion Top

The study contributes additional evidence from a distinctive sociocultural setting, to the literature on the relationship between paternal age and risk of ASDs, and it emphasizes the importance of replicating these findings across environments since increased paternal age may encapsulate both biological and sociocultural risk factors for adverse neurodevelopmental outcomes in offspring. Taken together with findings from other studies employing distinct research designs, these findings suggest that the paternal age effect is not explained by a selection effect in which fathers with autistic traits preferrentially delay parenting.

Acknowledgments Top

We would like to thank the Central Bureau of Statistics in Aruba for their ongoing contributions to our work. In particular we thank Karin Kock and Martijn Balkestein for their continued support.

Author Contributions Top

Conceived and designed the experiments: IvB MB ES HWH. Analyzed the data: PJV. Wrote the paper: IvB MB. Sampling frame/matching subjects to controls: IvB JH. Interpretation of the data: IvB MB HWH ES. Final approval: IvB MB PJV JH ES HWH.

References Top

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