Friday, March 4, 2011
Wednesday, March 2, 2011
Cayenne Stops a Heart Attack Instantly
Cayenne Stops a Heart Attack Instantly
Written by Canadafirst on 25 February 2011
Got heart trouble? Having a heart attack? Try Cayenne pepper. It will stop a heart attack in its tracks. Cayenne pepper is a very powerful vasodilator . It works faster than aspirin and has no side effects. Sprinkle a capsule worth in your Green tea. Use a tea spoon in hot hater and drink it down in case of chest pain and oncoming heart attack.
http://www.cayennepepper.info/health-benefits-of-cayenne-pepper.html
Yes, the effect of cayenne pepper on your body is dramatic, even literally instant and no more so than with the heart. Cayenne pepper’s benefits is one of the things that brought you to this article so now let’s discuss the phenomenal healing properties of cayenne pepper with the human heart.
Dr. John Christopher, the famed natural herbalist, was persecuted relentlessly by the government for his practice of herbal medicine all the while assisting patients in curing heart disease, cancer, tuberculosis, infertility, rheumatism, leukemia, and every other incurable under the sun.
One of his greatest stories in his long career was how he could instantly stop a heart attack if he could get the patient to drink a glass of warm cayenne water. He said, “A teaspoon of cayenne should bring the patient out of the heart attack.”
(NaturalNews) The late, famed herbalist Dr. John Christopher was nicknamed “Dr. Cayenne” because he was constantly recommending the healing powers of cayenne, the substance found in chili peppers that produces a sensation of heat. He especially advocated using it for cardiovascular health and even made the claim that doses of cayenne could stop heart attacks in progress (http://www.naturalnews.com/026869_c…). Now science has come up with proof cayenne does have a remarkable ability to help the heart. University of Cincinnati (UC) scientists have found that capsaicin, the main component of cayenne, may literally stop a heart attack in its tracks when applied topically.
New research just published in the journal Circulation concludes that a common, over-the-counter pain salve containing capsaicin rubbed on the skin during a heart attack could serve as a cardiac-protectant — reducing or even preventing damage to the heart. The researchers found an amazing 85 percent reduction in cardiac cell death when capsaicin was used. This is the most powerful cardioprotective effect ever recorded, according to Keith Jones, PhD, a researcher in the UC department of pharmacology and cell biophysics.
Dr. Jones and his research team applied capsaicin to specific skin locations in mice that caused reactions in the nervous system. Specifically, sensory nerves in the skin were triggered to activate what the scientists call cellular “pro-survival” pathways in the heart. The result? The heart muscle was protected from injury.
The researchers also found that a tiny incision made in the abdomen of the lab rodents triggered an 81 percent reduction in the death of heart cells. “Both this and the capsaicin effect are shown to work through similar neurological mechanisms,” Dr. Jones explained. “This is a form of remote cardioprotection, using a skin stimulus that activates cardioprotection long before the blocked coronary artery is opened.”
Dr. Jones is currently working in collaboration with cardiologist Neal Weintraub, MD, director of UC’s cardiovascular diseases division, and other clinicians to test capsaicin’s heart protective abilities in people. “Topical capsaicin has no known serious adverse effects and could be easily applied in an ambulance or emergency room setting well in advance of coronary tissue death,” Dr. Jones said in a media statement. “If proven effective in humans, this therapy has the potential to reduce injury and/or death in the event of a coronary blockage, thereby reducing the extent and consequences of heart attack.”
Learn more: http://www.naturalnews.com/027238_capsaicin_heart_attack_cayenne.html#ixzz1ExLWHoPE
Tags: attack, Health, Heart, pepper, stop
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Written by Canadafirst on 25 February 2011
Got heart trouble? Having a heart attack? Try Cayenne pepper. It will stop a heart attack in its tracks. Cayenne pepper is a very powerful vasodilator . It works faster than aspirin and has no side effects. Sprinkle a capsule worth in your Green tea. Use a tea spoon in hot hater and drink it down in case of chest pain and oncoming heart attack.
http://www.cayennepepper.info/health-benefits-of-cayenne-pepper.html
Yes, the effect of cayenne pepper on your body is dramatic, even literally instant and no more so than with the heart. Cayenne pepper’s benefits is one of the things that brought you to this article so now let’s discuss the phenomenal healing properties of cayenne pepper with the human heart.
Dr. John Christopher, the famed natural herbalist, was persecuted relentlessly by the government for his practice of herbal medicine all the while assisting patients in curing heart disease, cancer, tuberculosis, infertility, rheumatism, leukemia, and every other incurable under the sun.
One of his greatest stories in his long career was how he could instantly stop a heart attack if he could get the patient to drink a glass of warm cayenne water. He said, “A teaspoon of cayenne should bring the patient out of the heart attack.”
(NaturalNews) The late, famed herbalist Dr. John Christopher was nicknamed “Dr. Cayenne” because he was constantly recommending the healing powers of cayenne, the substance found in chili peppers that produces a sensation of heat. He especially advocated using it for cardiovascular health and even made the claim that doses of cayenne could stop heart attacks in progress (http://www.naturalnews.com/026869_c…). Now science has come up with proof cayenne does have a remarkable ability to help the heart. University of Cincinnati (UC) scientists have found that capsaicin, the main component of cayenne, may literally stop a heart attack in its tracks when applied topically.
New research just published in the journal Circulation concludes that a common, over-the-counter pain salve containing capsaicin rubbed on the skin during a heart attack could serve as a cardiac-protectant — reducing or even preventing damage to the heart. The researchers found an amazing 85 percent reduction in cardiac cell death when capsaicin was used. This is the most powerful cardioprotective effect ever recorded, according to Keith Jones, PhD, a researcher in the UC department of pharmacology and cell biophysics.
Dr. Jones and his research team applied capsaicin to specific skin locations in mice that caused reactions in the nervous system. Specifically, sensory nerves in the skin were triggered to activate what the scientists call cellular “pro-survival” pathways in the heart. The result? The heart muscle was protected from injury.
The researchers also found that a tiny incision made in the abdomen of the lab rodents triggered an 81 percent reduction in the death of heart cells. “Both this and the capsaicin effect are shown to work through similar neurological mechanisms,” Dr. Jones explained. “This is a form of remote cardioprotection, using a skin stimulus that activates cardioprotection long before the blocked coronary artery is opened.”
Dr. Jones is currently working in collaboration with cardiologist Neal Weintraub, MD, director of UC’s cardiovascular diseases division, and other clinicians to test capsaicin’s heart protective abilities in people. “Topical capsaicin has no known serious adverse effects and could be easily applied in an ambulance or emergency room setting well in advance of coronary tissue death,” Dr. Jones said in a media statement. “If proven effective in humans, this therapy has the potential to reduce injury and/or death in the event of a coronary blockage, thereby reducing the extent and consequences of heart attack.”
Learn more: http://www.naturalnews.com/027238_capsaicin_heart_attack_cayenne.html#ixzz1ExLWHoPE
Tags: attack, Health, Heart, pepper, stop
Posted in New
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Scientists say higher vitamin D intake will slash cancer, MS, and diabetes risk by half
Scientists say higher vitamin D intake will slash cancer, MS, and diabetes risk by half
Wednesday, March 02, 2011 by: S. L. Baker, features writer
(NaturalNews) In findings just published in the journal Anticancer Research, scientists at the University of California (UC) San Diego School of Medicine and Creighton University School of Medicine in Omaha have reported that most people need a much higher intake of vitamin D. And that simple step added to your life could slash your risk of developing serious diseases -- including cancer -- by about 50 percent.
The new study involved a survey of several thousand volunteers who took supplements containing 1000 to 10,000 IU per day. The researchers ran blood tests to measure the level of 25-vitamin D, which is the form of almost all vitamin D circulating in the bloodstream.
"We found that daily intakes of vitamin D by adults in the range of 4000 to 8000 IU are needed to maintain blood levels of vitamin D metabolites in the range needed to reduce by about half the risk of several diseases -- breast cancer, colon cancer, multiple sclerosis, and type 1 diabetes," Dr. Cedric Garland, professor of family and preventive medicine at UC San Diego Moores Cancer Center, said in a statement to media.
He added that the amount of vitamin D needed for disease prevention is far higher than the minimal dosage of 400 IU per day that was originally prescribed in the 20th century to treat and prevent rickets. However, upping vitamin D intake into the 4000 IU daily range and higher appears to be safe, according to a December 2010 report from the National Academy of Sciences Institute of Medicine.
"Most scientists who are actively working with vitamin D now believe that 40 to 60 ng/ml is the appropriate target concentration of 25-vitamin D in the blood for preventing the major vitamin D-deficiency related diseases, and have joined in a letter on this topic," Dr. Garland stated. "Unfortunately, according to a recent National Health and Nutrition Examination Survey, only 10 percent of the US population has levels in this range, mainly people who work outdoors."
Robert P. Heaney, MD, of Creighton University, a distinguished biomedical scientist, said he was not surprised by the new study's results based on his decades of research into the health benefits of vitamin D. "Now is the time for virtually everyone to take more vitamin D to help prevent some major types of cancer, several other serious illnesses, and fractures," Dr. Heaney said a statement to the press.
For more information:
http://www.iom.edu/Reports/2010/Die...
http://www.naturalnews.com/vitamin_...
Articles Related to This Article:
• Vitamin D Halts Growth of Breast Cancer Tumors
• Vitamin D prevents breast cancer
• Vitamin D is nutritional key for prevention of breast cancer
• Vitamin D prevents heart disease
• It's Winter - Do You Know Where Your Vitamin D Is?
• Sunlight emerging as proven treatment for breast cancer, prostate cancer and other cancers
Learn more: http://www.naturalnews.com/031560_vitamin_D_cancer.html#ixzz1FTCZsADV
Wednesday, March 02, 2011 by: S. L. Baker, features writer
(NaturalNews) In findings just published in the journal Anticancer Research, scientists at the University of California (UC) San Diego School of Medicine and Creighton University School of Medicine in Omaha have reported that most people need a much higher intake of vitamin D. And that simple step added to your life could slash your risk of developing serious diseases -- including cancer -- by about 50 percent.
The new study involved a survey of several thousand volunteers who took supplements containing 1000 to 10,000 IU per day. The researchers ran blood tests to measure the level of 25-vitamin D, which is the form of almost all vitamin D circulating in the bloodstream.
"We found that daily intakes of vitamin D by adults in the range of 4000 to 8000 IU are needed to maintain blood levels of vitamin D metabolites in the range needed to reduce by about half the risk of several diseases -- breast cancer, colon cancer, multiple sclerosis, and type 1 diabetes," Dr. Cedric Garland, professor of family and preventive medicine at UC San Diego Moores Cancer Center, said in a statement to media.
He added that the amount of vitamin D needed for disease prevention is far higher than the minimal dosage of 400 IU per day that was originally prescribed in the 20th century to treat and prevent rickets. However, upping vitamin D intake into the 4000 IU daily range and higher appears to be safe, according to a December 2010 report from the National Academy of Sciences Institute of Medicine.
"Most scientists who are actively working with vitamin D now believe that 40 to 60 ng/ml is the appropriate target concentration of 25-vitamin D in the blood for preventing the major vitamin D-deficiency related diseases, and have joined in a letter on this topic," Dr. Garland stated. "Unfortunately, according to a recent National Health and Nutrition Examination Survey, only 10 percent of the US population has levels in this range, mainly people who work outdoors."
Robert P. Heaney, MD, of Creighton University, a distinguished biomedical scientist, said he was not surprised by the new study's results based on his decades of research into the health benefits of vitamin D. "Now is the time for virtually everyone to take more vitamin D to help prevent some major types of cancer, several other serious illnesses, and fractures," Dr. Heaney said a statement to the press.
For more information:
http://www.iom.edu/Reports/2010/Die...
http://www.naturalnews.com/vitamin_...
Articles Related to This Article:
• Vitamin D Halts Growth of Breast Cancer Tumors
• Vitamin D prevents breast cancer
• Vitamin D is nutritional key for prevention of breast cancer
• Vitamin D prevents heart disease
• It's Winter - Do You Know Where Your Vitamin D Is?
• Sunlight emerging as proven treatment for breast cancer, prostate cancer and other cancers
Learn more: http://www.naturalnews.com/031560_vitamin_D_cancer.html#ixzz1FTCZsADV
Tuesday, March 1, 2011
The Spice that Helps Prevent Cancer - Now Being Used to Repair Stroke Damage Posted By Dr. Mercola
March 02 2011
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PreviousNextScientists have created a new molecule from curcumin, the key chemical component of the spice turmeric. In laboratory experiments, the molecule was shown to affect the mechanisms that protect and regenerate brain cells after a stroke.
The new curcumin compound, called CNB-001, actually repairs stroke damage at the molecular level.
Physorg reports:
"Those who cook Indian, Thai, Malay and Persian dishes know turmeric well for its zesty flavor, use in curries and for the rich color it imparts to food. Turmeric also has a long history of use in Ayurvedic and Chinese traditional medicine."
Sources:
Physorg February 10, 2011
Dr. Mercola's Comments:
Curcumin -- the pigment that gives the curry spice turmeric its yellow-orange color -- is a natural compound that should be on your health radar for a number of reasons. Both the ancient Chinese and Indian systems of medicine have recognized curcumin's beneficial properties for thousands of years, and modern research suggests it may be one of nature's most powerful potential healers.
As you'll see, its health benefits are far-reaching and are now entering the arena of emergency medicine.
In this article I will also review several natural strategies for preventing stroke, as there are other lifestyle and dietary factors that play a massive role. You really don't want to wait until a stroke happens, regardless of how effectively drugs might help to keep you alive.
So What is a Stroke?
Strokes are sometimes referred to as "brain attacks" (instead of "heart attacks") because they occur when a blood clot blocks an artery or blood vessel, cutting off blood flow to your brain. As a result, brain cells die and brain damage can occur.
Strokes can be particularly devastating because they often occur without warning, and the longer your brain goes without oxygen, the greater your risk of lasting damage. This is one area where emergency medicine excels, as emergency medications can dissolve the clot that is blocking blood flow to your brain. In order to be effective, however, you typically need to get help within one hour.
So if you notice any of these signs of stroke, you should get help right away:
•Sudden trouble walking (dizziness, loss of balance, etc.)
•Sudden confusion
•Sudden numbness or weakness (especially on one side of your body only)
•Sudden trouble seeing
•Sudden severe headache
Curcumin Drug May Help Regenerate Brain Cells after Stroke
Contrary to the clot-busting drug currently used on stroke victims, the curcumin-hybrid compound, called CNB-001, does not actually dissolve the blood clot. Rather it repairs the damage incurred by the lack of oxygen, at the molecular level, by influencing the mechanism responsible for regeneration of neurons (brain cells).
This offers future stroke victims new hope for greater recovery, as it may reduce lasting damage. The research was presented at the American Heart Association International Stroke Conference in Los Angeles on February 9.
Now, although curcumin itself has been found to have great healing potential, including in the treatment of brain injury, it has drawbacks that makes it unsuitable for emergency treatment of stroke.
Physorg reports:
"[Curcumin] is not well absorbed in the body, fails to reach its target in high concentrations, becomes depleted quickly, and is blocked from entering the brain by a natural protective mechanism called the blood-brain barrier."
The curcumin-derived compound CNB-001, however, does cross the blood brain barrier and "moderates several critical mechanisms involved in neuronal survival," according to lead researcher Dr. Lapchak, PhD.
What this means is that if you're having signs of stroke, do not reach for the spice jar or a turmeric supplement. Seek immediate emergency medical attention! Turmeric cannot be used as a make-shift home-remedy for a stroke. I just want to make that perfectly clear.
The hybrid spice-drug compound may however help save lives in an emergency setting later on. According to Physorg's report:
"The drug reduced stroke-caused "motor deficits"—problems of muscle and movement control—in this laboratory study. It was effective when administered up to an hour after stroke, which correlates with about three hours in humans, the same time frame for which tPA is currently approved."
There's a time and place for conventional medicine, and stroke is one of those times when a drug can save your life. That said, considering how devastating (not to mention life threatening) a stroke can be, it would be in your best interest to adjust your lifestyle to prevent it from ever happening in the first place.
This Common Vitamin Deficiency DOUBLES Your Risk of Stroke!
What vitamin could this possibly be?
If you guessed vitamin D, you're absolutely correct. This was the impressive finding of a study presented on November 15 last year at the American Heart Association's (AHA) annual Scientific Sessions in Chicago.
It adds weight to research released earlier last year, which found that vitamin D deficiency is associated with arterial stiffness; a risk factor for heart disease and stroke. A separate study from Finland also found that those with the lowest vitamin D levels had a 25 percent higher risk of dying from heart disease or stroke, and when only stroke was evaluated, those with the lowest levels had twice the risk as those with the highest vitamin D levels.
In the past couple of years, research into the health benefits of vitamin D and the serious ramifications of deficiency has exploded. The evidence that vitamin D is a key player in your health is just overwhelming.
For example, optimizing your vitamin D levels can also slash your risk of diabetes and cancer in half! And that's still just the tip of the iceberg.
What other drug or nutrient do you know of that can cut your risk of three of the most dangerous chronic diseases by 50 percent?!
It's abundantly clear that if you want optimal health, you need to pay attention to your vitamin D levels. Ideally, you'll want to increase your levels through safe sunshine exposure year-round. Not only is this the way you were designed to produce vitamin D naturally, but it also eliminates the risk of overdosing. You can also use a safe tanning bed if you can't get sufficient amounts of sun exposure outdoors.
If neither of those options are available to you, consider taking a vitamin D3 supplement, but be sure to get your vitamin D levels tested regularly to make sure you're staying within therapeutic limits, as you're circumventing your body's built-in regulatory mechanism.
For more information about safe sun exposure, testing, and dosages, please see my vitamin D page. I also recommend viewing my one-hour video lecture on vitamin D to get a deeper understanding of its vital importance to your health.
Other Stroke Prevention Strategies
Up to 80 percent of strokes are preventable, according to the National Stroke Association, so I strongly encourage you to take control of your health to reduce your risk. Conventionally speaking, many of the same risk factors that increase your risk of heart disease also increase your risk of stroke, such as:
•High blood pressure
•Obesity
•High triglycerides and elevated homocysteine levels
•Low levels of HDL (good) cholesterol and high levels of LDL (bad) cholesterol
•Smoking
So, as with your heart, eating unprocessed, natural foods, exercising, getting regular sun exposure, and maintaining a healthy weight will help to reduce your risk of stroke.
Also high up on the list of keys to preventing a stroke is to get a handle on your stress levels as the more stressed you are, the greater your risk. As an example, a study published in the journal Neurology found that psychological distress will greatly increase your risk of suffering a stroke. The researchers actually found that for every notch lower a person scored on their well-being scale, their risk of stroke increased by 11 percent.
Not surprisingly, the relationship between psychological distress and stroke was most pronounced when the stroke was fatal.
So while optimizing your vitamin D levels and leading a healthy lifestyle with nutritious food and regular exercise are important, you'll want to be sure you tend to your emotional health as well.
More Health Benefits of Curcumin
Now that we've reviewed the strategies that can help prevent you from becoming another stroke statistic, let's get back to curcumin, because this spice compound—which is also available in supplement form—has many other potent health benefits.
Most notably, curcumin is known for its potent anti-inflammatory properties, and chronic inflammation is the hallmark of most chronic disease, including diabetes, arthritis, and heart disease, just to name a few. The compound has been shown to influence more than 700 genes, and it can inhibit both the activity and the synthesis of cyclooxygenase-2 (COX2) and 5-lipooxygenase (5-LOX), as well as other enzymes that have been implicated in inflammation.
But that's not all. Other health benefits include:
•Strengthening and improving your digestion
•Supporting healthy liver function and detoxification
•Purifying your blood
Further, evidence suggests turmeric may play a beneficial role in the following diseases:
•Cystic fibrosis
•Type 2 diabetes
•Inflammatory bowel disease, Crohn’s disease
•Psoriasis
•Rheumatoid arthritis
•Cataracts
•Gallstones
•Muscle regeneration
•Alzheimer’s disease
Curcumin—One of the BEST Supplements for Many Cancers Too!
If you want to use curcumin to prevent stroke I believe your best strategy is to use it as a food in the form of turmeric. However if you have a severe illness, like cancer, then it is best to use it as a drug at a much higher dose as described below.
Dr. William LaValley from Austin Texas is one of the top natural medicine cancer physicians I know and he recently shared this important information on curcumin, which has the most evidence based literature for use as a cancer support than any other nutrient.
Curcumin affects more than 100 different pathways once it gets into the cell. Interestingly this also includes the metabolite of curcumin and its derivatives, which are also anti-cancer. Best of all, curcumin appears to be safe in the treatment of all cancers.
In India where turmeric is widely used, the prevalence of four common U.S. cancers -- colon, breast, prostate and lung -- is 10 times lower. In fact, prostate cancer, which is the most frequently diagnosed cancer in U.S. men, is rare in India and this is attributed, in part, to the curcumin in turmeric.
Numerous studies have looked into this potential cancer-fighting link, with promising results. For instance, curcumin has been found to:
•Inhibit the proliferation of tumor cells
•Inhibit the transformation of cells from normal to tumor
•Help your body destroy mutated cancer cells so they cannot spread throughout your body
•Decrease inflammation
•Enhance liver function
•Inhibit the synthesis of a protein thought to be instrumental in tumor formation
•Prevent the development of additional blood supply necessary for cancer cell growth
And, according to researchers from the University of Texas M.D. Anderson Cancer Center, curcumin blocks a key biological pathway needed for development of melanoma and other cancers.
The spice actually stops laboratory strains of melanoma from proliferating and pushes the cancer cells to die by shutting down nuclear factor-kappa B (NF-kB), a powerful protein known to induce abnormal inflammatory response that leads to an assortment of disorders such as arthritis and cancer.
To get the full benefits that curcumin has to offer, you will want to look for a turmeric extract with at least 95 percent curcuminoids that contains only 100 percent certified organic ingredients.
The formula should be free of fillers, additives and excipients (a substance added to the supplement as a processing or stability aid), and the manufacturer should use safe production practices at all stages: planting, cultivation, selective harvesting, and then producing and packaging the final product.
Details on How to Use Curcumin
The unfortunate challenge at this time is that good formulations of curcumin to use in cancer still aren't available. This is because relatively high doses are required and curcumin is not absorbed that well. Typical anticancer doses are up to three grams of good bioavailable curcmin extract, three to four times a day.
One work-around for this is to use curcumin powder and make a microemulsion of it by combining a tablespoon of the powder and mixing it into 1-2 egg yolks, and a teaspoon or two of melted coconut oil. Then use a high-speed hand blender to emulsify the powder.
Another strategy to increase absorption is to put one tablespoon of the curcumin powder into a quart of boiling water. It must be boiling when you add the powder as it will not work as well if you put it in room temperature water and then heat the water with the curcumin already in it. After boiling it for 10 minutes, you will have created a 12 percent solution, which you can drink once it has cooled down. The curcumin will gradually fall out of solution over time and in about six hours it will be a 6 percent solution, so it is best to drink the water within four hours. It does have a woody taste.
One caution to know is that you want to avoid the "yellow kitchen" syndrome. Curcumin is a very potent yellow pigment and can permanently discolor surfaces if you aren't careful.
Related Links:
Strokes Triple Among Middle-Aged Women
'Holy Powder' Makes Your Cell Membranes Behave for Better Health
New Hope for Natural Weight Loss
Vitamin D Supplement Doses and Serum 25-Hydroxyvitamin D in the Range Associated with Cancer Prevention
Vitamin D Supplement Doses and Serum 25-Hydroxyvitamin D in the Range Associated with Cancer Prevention
CEDRIC F. GARLAND1, CHRISTINE B. FRENCH2, , LEO L. BAGGERLY3, and ROBERT P. HEANEY4,
"This paper provides a long awaited insight into a dose-response relationship between orally administered vitamin D3 and the resulting levels of serum 25(OH)D in over 3600 citizens. The results will allow new definition of high vitamin D dose safety and reduce concerns about toxicity. This is a landmark contribution in the vitamin D nutrition field!"
Anthony Norman
Distinguished Professor of Biochemistry & Biomedical Sciences, Emeritus
University of California Riverside
Abstract. Background: Studies indicate that intake of vitamin D in the range from 1,100 to 4,000 IU/d and a serum 25- hydroxyvitamin D concentration [25(OH)D] from 60-80 ng/ml may be needed to reduce cancer risk. Few community-based studies allow estimation of the dose–response relationship between oral intake of vitamin D and corresponding serum 25(OH)D in the range above 1,000 IU/d. Materials and Methods: A descriptive study of serum 25(OH)D concentration and self-reported vitamin D intake in a community-based cohort (n=3,667, mean age 51.3±13.4 y). Results: Serum 25(OH)D rose as a function of self-reported vitamin D supplement ingestion in a curvilinear fashion, with no intakes of 10,000 IU/d or lower producing 25(OH)D values above the lower-bound of the zone of potential toxicity (200 ng/ml). Unsupplemented all-source input was estimated at 3,300 IU/d. The supplemental dose ensuring that 97.5% of this population achieved a serum 25(OH)D of at least 40 ng/ml was 9,600 IU/d. Conclusion: Universal intake of up to 40,000 IU vitamin D per day is unlikely to result in vitamin D toxicity.
The recent increase in interest in vitamin D by the general public has fueled a better than 200% increase in sales of overthe- counter vitamin D preparations from 2008 to 2009, and a more than 6-fold increase since 2001 (1). Additionally, products with progressively increasing content of vitamin D have been introduced with similar rapidity. There seems to have been little precedent for a change of this magnitude and duration for other nutrients (e.g., vitamins C and E) that have enjoyed brief periods of popularity among the general public. There is essentially no information on how the public uses these products or on their impact on the vitamin D status of consumers.
GrassrootsHealth (GRH), a non-profit community service organization dedicated to promoting public awareness about vitamin D, has assembled a database that includes information on supplemental vitamin D intake by a selfselected population cohort, and links these intakes to measured values for serum 25(OH)D, various demographic variables, and a variety of health status measures. GRH data include values from many individuals with daily supplemental intakes in and above the ranges often used today for cancer prevention and co-therapy (2, 3).
This study used the GRH database to describe the relationship of measured vitamin D status to vitamin D supplementation, both as practiced by health conscious individuals and as related to cancer prevention.
Materials and Methods
Participants. The initial participants in the study were individuals who responded to an invitation issued to all attendees at aVitamin D Seminar hosted by GRH in December, 2008, supplemented by extensive recruitment from internet invitations since then. There were no exclusion criteria, and participants included both genders and a wide range of ages, nationalities and levels of health status. Participation included receiving a test of serum 25(OH)D concentration and an on-line health questionnaire to be completed each six months for a suggested period of five years. The purpose of the latter was to enable determination of what health outcomes are associated with various serum 25(OH)D concentrations. GRH provided the participants with a blood spot 25(OH)D test kit manufactured by ZRT Laboratory (Beaverton, OR, USA). After each test, the participants received an email message from GRH indicating that their test scores were available. If desired, they then logged into their account to view the results. Included in the test results were the normal reference ranges, information about potential toxicity levels, and suggested serum 25(OH)D concentrations (40-60 ng/ml). Participants chose for themselves what actions to take. The project costs were funded entirely by participant fees. This project, analyzing anonymized GRH data, was reviewed by the Creighton University Institutional Review Board and declared ‘exempt’.
Analytical methods. Serum 25(OH)D concentrations were determined by the ZRT blood spot test kit. The analytical method used was high-performance liquid chromatography followed by mass spectroscopy and has been validated against the DiaSorin RIA method with an r2 value of 0.91 and with a slope not different from 1.0 (4). Participants obtained their own blood spots, dried them, and returned them to GRH in supplied mailers. The dried blood spots have been shown to be stable at room temperature with regard to serum 25(OH)D concentration for at least four months.
Statistical analysis. The accumulated data were stored in a MySQL database (Ver. 5.0.77 Oracle USA, Redwood City, CA, USA), operating behind a firewall, and password protected. Data extracts were exported to Microsoft Excel (Microsoft Corp., Redmond, WA, USA). Analysis was by the various statistical routines of Excel and SigmaPlot 11.0 (Systat Software Inc., San Jose, CA, USA). The relationship of oral vitamin D supplement intake to serum 25(OH)D concentration was fitted to the following equation, using the curvefitting routine of SigmaPlot.
Y=Y0 + a(1 – e–bX) + cX ,
where Y=serum 25(OH)D, X=vitamin D dose (in 1,000s IU/d). As the equation shows, it contains three terms: (i) the zero dose value of 25(OH)D (Y0); (ii) an expression describing the saturable exponential component relating to hepatic 25-hydroxylation; and (iii) a linear term relating to zero-order kinetics for 25-hydroxylase (5). Specifically: a=the 25(OH)D increment at maximum saturation of the hepatic 25-hydroxylase, b=the rate constant of the process, and c=the coefficient of the linear rise in serum 25(OH)D. In addition to other statistics, the curve-fitting routine provides the standard error of the estimate (SEE) around the fitted mean. The 95% probability range for the 25(OH)D concentration values is thus ±1.96 SEE.
Results
Table I sets forth the pertinent demographic information with respect to the participant cohort, and Figure 1 presents a frequency distribution of self-reported daily vitamin D intakes. A large majority of the participants were non-Hispanic whites (N-H Whites), ingesting 5,000 IU/d or lower. Approximately one-fourth of the cohort reported no supplemental vitamin D intake; another 47% reported intakes up to 2,000 IU/d; and 1.8% reported intakes above 10,000 IU/d (n=60). There is an evident skewing of the intake distribution to the right. The relationship between reported vitamin D intake and measured serum 25(OH)D concentration is plotted in Figure 2, which includes also the best fit line for the data using Equation 1. Figure 2 demonstrates several points: (i) the tendency for serum 25(OH)D to rise with increasing dosage is much more gradual than might have been anticipated from extrapolation of the relationship at more usual, lower intakes; (ii) there is a very large spread of values around the regression line, consistent with what most other studies have found (e.g., 6); and (iii) despite there being in some individuals clearly supraphysiological inputs, very few individuals had serum 25(OH)D values above the 200 ng/ml lower boundary for potential toxicity described by Hathcock et al. (7) and Vieth (8).
The value of the Y0 parameter (32.9 ng/ml ±0.483 SEM, Figure 2) is the zero supplement value for this cohort, reflecting vitamin D inputs solely from cutaneous solar UVB photosynthesis and food. In brief, the X-axis zero value does not reflect actual zero input, just zero supplemental input. Using Equation 1 and extrapolating the curve to the left produces a true zero 25(OH)D value at approximately –3,300 IU/d. In other words 3,300 IU/d is the approximate magnitude of the rightward translation exhibited by the Xaxis and, correspondingly, that value approximates the mean non-supplemental vitamin D input for this participant cohort.
The fitting routine was applied, not only to the whole data set, as in Figure 2, but to various subsets, based on gender and ethnicity. Men and women exhibited nearly identical fits at intakes below 10,000 IU/d, but the rise at intakes above 10,000 was nearly flat for men. However, there were relatively few instances of such intakes in the 1,436 men in this sample; hence this issue remains uncertain. There were too few data for those in the ‘Black’ category (n=33) to permit curve-fitting, but by direct calculation, their zero supplement serum 25(OH)D concentration was 18.0 (±9.5) ng/ml, significantly lower than for N-H Whites, for whomY0=33.4 (±26.4) ng/ml (p<0.001). The ‘Other’ ethnicity category (largely Eastern Asiatics; n=230) had sufficient data to permit fitting to Equation 1. Its parameters did not differ appreciably from those of the N-H White group, except for the Y0 estimate, which was 26.6 (±23.7) ng/ml, also significantly lower than the Y0 parameter estimate for N-H Whites (p<0.001). These differences are consistent with expectations based on skin pigmentation.
Because obesity is recognized to be associated with low vitamin D status, the residuals from the above curve fit were regressed against body weight and demonstrated the expected inverse relationship (r2=0.03). While statistically significant (p<0.01), this relation failed to account for most of the between-participant variance.
A question frequently asked by clinicians is how much of an increase in serum 25(OH)D should be expected for a given additional oral dose of vitamin D. Figure 3 provides an answer by plotting the first derivative of the equation in Figure 2 at various starting values. For example, at a starting value of 10 ng/ml, the mean increment that would be expected to be produced by an additional 1,000 IU/d is 11 ng/ml, whereas at 30 ng/ml it is 8 ng/ml, and at 50 ng/ml, only 5 ng/ml. Above a starting value of 90 ng/ml, the response is nearly flat at about 1.6 ng/ml/1,000 IU/d.
Because no serum 25(OH)D method has been specifically calibrated against standards above 100 ng/ml, the accuracy of the 25(OH)D values was assessed by superimposing the regression line from Figure 2 on previously published data (8) relating high-dose vitamin D intake to serum 25(OH)D. The results are shown as Figure 4. It is immediately apparent that the regression line from the blood spot method used in the present study superimposes on the data points previously published by Vieth (8), at least out to 100,000 IU/d, which is as far as the GRH data extend.
Discussion
To the Authors’ knowledge this is the first analysis of the relation of vitamin D status to voluntary vitamin D supplementation as practiced in the community. The community base, the size of the sample, and the completeness of the pertinent data are strengths. Weaknesses include the fact that no single vitamin D product was used, the products themselves were not evaluated for exact vitamin D content and the doses are self-reported. Additionally, the data are cross-sectional and cannot give a true picture of individual responses to dose changes. Nevertheless, several features of the current findings indicate that these limitations do not preclude drawing useful conclusions from these data.
As noted above, the fit derived from the total data set superimposes on the high-dose data assembled by Vieth (8). Additionally, the general shape of the curve (exponential at low intakes and linear at high) is precisely mirrored in an earlier publication by Heaney et al. (5), relating the serum concentrations of 25(OH)D and cholecalciferol, in which the inflection point between the linear and exponential components occurred at a serum 25(OH)D concentration of ~35 ng/ml, corresponding to a serum vitamin D concentration of ~4 ng/ml. These values are very similar to the pertinent parameters of the equation used here to describe the GRH data set. Both of these agreements among studies support the overall validity of the data in the present report.
The 95% probability bands in Figure 2 provide useful information on the dosages required to ensure that a specified fraction of the population would have 25(OH)D concentrations above any given level. Such inferences are not affected by the cross-sectional character of the data. The points where that lower band crosses 30, 40, and 50 ng/ml (75, 100, and 125 nmol/l) are the supplemental intake values that ensure that 97.5% of the population would be above the specified serum 25(OH)D concentrations concerned. These are, respectively, 6,100, 9,600, and 14,100 IU/d for this population. Observed mean (SD) 25(OH)D concentrations at these intakes are, respectively 64.6 (±18), 75.1 (±18), and 85.2 (±18) ng/ml. Given that the average, non-supplemental intake in this cohort was estimated to be ~3,300 IU/d, the total intake from a vitamin D-deprived basal state which would be required to ensure that all but 2.5% of the population would reach the specified serum 25(OH)D levels would be 9,400, 12,900, and 17,400 IU/d. Although an order of magnitude higher than currently recommended oral intakes (9), these calculated daily intakes are of the same magnitude as produced by a single, minimal erythemal dose of UV-B radiation, such as would be obtained during a few minutes of solar UVB exposure near noon in midsummer, assuming nearly complete skin exposure (10).
Although this data set provides no information with respect to serum or urine calcium values in these individuals, at the same time it is clear that there were no clinical evidences of toxicity. Indeed, since virtually all of the values, at whatever dose, were associated with 25(OH)D values below 200 ng/ml [and no doses below 50,000 IU/d produced serum 25(OH) D values above 200 ng/ml], the absence of apparent toxicity is not surprising. The very slow rise in serum 25(OH)D concentration for each 1,000 IU increment at serum values above 80-100 ng/ml (Figure 3) is firm expression of the general safety of even relatively high doses.
A prominent feature of this cohort is that it is self-selected for health consciousness. Hence, in terms of dosing choices, this cohort cannot be considered representative of the general population. Accordingly, given this cohort’s likely high degree of adherence to supplementation, the achieved vitamin D status values are almost certainly higher than would be expected in less-motivated members of the general public.
Finally, and as an incidental observation, these data suggest a possible insight into the pathogenesis of toxicity. It is suggested that such an outcome requires two conditions: (i) high dose and (ii) high individual responsiveness to any given dose. As Ilahi et al. (6) reported previously, values for Cmax following a single dose of 100,000 IU spanned a six-fold range from 4.9 ng/ml to 30.8 ng/ml. Had that dosing been continued (as in the high-dose members of the GRH cohort), a person with a 30.8 ng/ml increase would likely have exceeded a serum 25(OH)D concentration of 200 ng/ml, whereas a person at the low end of the range for Cmax, would not have.
Acknowledgements
Participant recruitment and data management for this study was provided by GrassrootsHealth. The Authors wish to thank Carole Baggerly, Director of GrassrootsHealth for her invaluable assistance and encouragement and the participants who provided the funding and the information for this study.
References
1.Nutrition Business Journal; 2010 Supplement Business Report, Sept. 28, 2010.
2.Garland CF, Gorham ED, Mohr SB and Garland FC: Vitamin D for cancer prevention: global perspective. Ann Epidemiol 19: 468-483, 2009.
3.Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, Newmark H, Holick MF, and Garland FC: Vitamin D and prevention of breast cancer: Pooled analysis. J Steroid Biochem Molec Biol 103: 708-711, 2007.
4.Eyles D, Anderson C, Ko P, Jones A, Thomas A, Burne T, Mortensen PB, Nørgaard-Pedersen B, Hougaard DM and McGrath J: A sensitive LC/MS/MS assay of 25OH vitamin D(3) and 25OH vitamin D(2) in dried blood spots. Clin Chim Acta 403: 145-151, 2009.
5.Heaney RP, Armas LAG, Shary JR, Bell NH, Binkley N and Hollis BW: 25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under varying input conditions. Am J Clin Nutr 87: 1730-1737, 2008.
6.Ilahi M, Armas LAG and Heaney RP: The pharmacokinetics of a single large dose of vitamin D3. Am J Clin Nutr 87: 688-691, 2008.
7.Hathcock JN, Shao A, Vieth R and Heaney RP: Risk assessment for vitamin D. Am J Clin Nutr 85: 6-18, 2007. 8 Vieth R: Vitamin D and cancer mini-symposium: the risk of additional vitamin D. Ann Epidemiol 19: 441-445, 2009.
8.Vieth R: Vitamin D and cancer mini-symposium: the risk of additional vitamin D. Ann Epidemiol 19: 441-445, 2009.
9.IOM (Institute of Medicine). 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press.
10.Webb AR and Holick MF: The role of sunlight in the cutaneous production of vitamin D3. Ann Rev Nutr 8: 375-399, 1988.
Received December 22, 2010
Revised January 18, 2011
Accepted January 19, 2011
1University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, U.S.A.;
2GrassrootsHealth, P.O. Box 234208, Encinitas, CA 92023, U.S.A.;
3Creighton University, 2500 California Plaza, Omaha, NE 68178, U.S.A.
Anticancer Research
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CEDRIC F. GARLAND1, CHRISTINE B. FRENCH2, , LEO L. BAGGERLY3, and ROBERT P. HEANEY4,
"This paper provides a long awaited insight into a dose-response relationship between orally administered vitamin D3 and the resulting levels of serum 25(OH)D in over 3600 citizens. The results will allow new definition of high vitamin D dose safety and reduce concerns about toxicity. This is a landmark contribution in the vitamin D nutrition field!"
Anthony Norman
Distinguished Professor of Biochemistry & Biomedical Sciences, Emeritus
University of California Riverside
Abstract. Background: Studies indicate that intake of vitamin D in the range from 1,100 to 4,000 IU/d and a serum 25- hydroxyvitamin D concentration [25(OH)D] from 60-80 ng/ml may be needed to reduce cancer risk. Few community-based studies allow estimation of the dose–response relationship between oral intake of vitamin D and corresponding serum 25(OH)D in the range above 1,000 IU/d. Materials and Methods: A descriptive study of serum 25(OH)D concentration and self-reported vitamin D intake in a community-based cohort (n=3,667, mean age 51.3±13.4 y). Results: Serum 25(OH)D rose as a function of self-reported vitamin D supplement ingestion in a curvilinear fashion, with no intakes of 10,000 IU/d or lower producing 25(OH)D values above the lower-bound of the zone of potential toxicity (200 ng/ml). Unsupplemented all-source input was estimated at 3,300 IU/d. The supplemental dose ensuring that 97.5% of this population achieved a serum 25(OH)D of at least 40 ng/ml was 9,600 IU/d. Conclusion: Universal intake of up to 40,000 IU vitamin D per day is unlikely to result in vitamin D toxicity.
The recent increase in interest in vitamin D by the general public has fueled a better than 200% increase in sales of overthe- counter vitamin D preparations from 2008 to 2009, and a more than 6-fold increase since 2001 (1). Additionally, products with progressively increasing content of vitamin D have been introduced with similar rapidity. There seems to have been little precedent for a change of this magnitude and duration for other nutrients (e.g., vitamins C and E) that have enjoyed brief periods of popularity among the general public. There is essentially no information on how the public uses these products or on their impact on the vitamin D status of consumers.
GrassrootsHealth (GRH), a non-profit community service organization dedicated to promoting public awareness about vitamin D, has assembled a database that includes information on supplemental vitamin D intake by a selfselected population cohort, and links these intakes to measured values for serum 25(OH)D, various demographic variables, and a variety of health status measures. GRH data include values from many individuals with daily supplemental intakes in and above the ranges often used today for cancer prevention and co-therapy (2, 3).
This study used the GRH database to describe the relationship of measured vitamin D status to vitamin D supplementation, both as practiced by health conscious individuals and as related to cancer prevention.
Materials and Methods
Participants. The initial participants in the study were individuals who responded to an invitation issued to all attendees at aVitamin D Seminar hosted by GRH in December, 2008, supplemented by extensive recruitment from internet invitations since then. There were no exclusion criteria, and participants included both genders and a wide range of ages, nationalities and levels of health status. Participation included receiving a test of serum 25(OH)D concentration and an on-line health questionnaire to be completed each six months for a suggested period of five years. The purpose of the latter was to enable determination of what health outcomes are associated with various serum 25(OH)D concentrations. GRH provided the participants with a blood spot 25(OH)D test kit manufactured by ZRT Laboratory (Beaverton, OR, USA). After each test, the participants received an email message from GRH indicating that their test scores were available. If desired, they then logged into their account to view the results. Included in the test results were the normal reference ranges, information about potential toxicity levels, and suggested serum 25(OH)D concentrations (40-60 ng/ml). Participants chose for themselves what actions to take. The project costs were funded entirely by participant fees. This project, analyzing anonymized GRH data, was reviewed by the Creighton University Institutional Review Board and declared ‘exempt’.
Analytical methods. Serum 25(OH)D concentrations were determined by the ZRT blood spot test kit. The analytical method used was high-performance liquid chromatography followed by mass spectroscopy and has been validated against the DiaSorin RIA method with an r2 value of 0.91 and with a slope not different from 1.0 (4). Participants obtained their own blood spots, dried them, and returned them to GRH in supplied mailers. The dried blood spots have been shown to be stable at room temperature with regard to serum 25(OH)D concentration for at least four months.
Statistical analysis. The accumulated data were stored in a MySQL database (Ver. 5.0.77 Oracle USA, Redwood City, CA, USA), operating behind a firewall, and password protected. Data extracts were exported to Microsoft Excel (Microsoft Corp., Redmond, WA, USA). Analysis was by the various statistical routines of Excel and SigmaPlot 11.0 (Systat Software Inc., San Jose, CA, USA). The relationship of oral vitamin D supplement intake to serum 25(OH)D concentration was fitted to the following equation, using the curvefitting routine of SigmaPlot.
Y=Y0 + a(1 – e–bX) + cX ,
where Y=serum 25(OH)D, X=vitamin D dose (in 1,000s IU/d). As the equation shows, it contains three terms: (i) the zero dose value of 25(OH)D (Y0); (ii) an expression describing the saturable exponential component relating to hepatic 25-hydroxylation; and (iii) a linear term relating to zero-order kinetics for 25-hydroxylase (5). Specifically: a=the 25(OH)D increment at maximum saturation of the hepatic 25-hydroxylase, b=the rate constant of the process, and c=the coefficient of the linear rise in serum 25(OH)D. In addition to other statistics, the curve-fitting routine provides the standard error of the estimate (SEE) around the fitted mean. The 95% probability range for the 25(OH)D concentration values is thus ±1.96 SEE.
Results
Table I sets forth the pertinent demographic information with respect to the participant cohort, and Figure 1 presents a frequency distribution of self-reported daily vitamin D intakes. A large majority of the participants were non-Hispanic whites (N-H Whites), ingesting 5,000 IU/d or lower. Approximately one-fourth of the cohort reported no supplemental vitamin D intake; another 47% reported intakes up to 2,000 IU/d; and 1.8% reported intakes above 10,000 IU/d (n=60). There is an evident skewing of the intake distribution to the right. The relationship between reported vitamin D intake and measured serum 25(OH)D concentration is plotted in Figure 2, which includes also the best fit line for the data using Equation 1. Figure 2 demonstrates several points: (i) the tendency for serum 25(OH)D to rise with increasing dosage is much more gradual than might have been anticipated from extrapolation of the relationship at more usual, lower intakes; (ii) there is a very large spread of values around the regression line, consistent with what most other studies have found (e.g., 6); and (iii) despite there being in some individuals clearly supraphysiological inputs, very few individuals had serum 25(OH)D values above the 200 ng/ml lower boundary for potential toxicity described by Hathcock et al. (7) and Vieth (8).
The value of the Y0 parameter (32.9 ng/ml ±0.483 SEM, Figure 2) is the zero supplement value for this cohort, reflecting vitamin D inputs solely from cutaneous solar UVB photosynthesis and food. In brief, the X-axis zero value does not reflect actual zero input, just zero supplemental input. Using Equation 1 and extrapolating the curve to the left produces a true zero 25(OH)D value at approximately –3,300 IU/d. In other words 3,300 IU/d is the approximate magnitude of the rightward translation exhibited by the Xaxis and, correspondingly, that value approximates the mean non-supplemental vitamin D input for this participant cohort.
The fitting routine was applied, not only to the whole data set, as in Figure 2, but to various subsets, based on gender and ethnicity. Men and women exhibited nearly identical fits at intakes below 10,000 IU/d, but the rise at intakes above 10,000 was nearly flat for men. However, there were relatively few instances of such intakes in the 1,436 men in this sample; hence this issue remains uncertain. There were too few data for those in the ‘Black’ category (n=33) to permit curve-fitting, but by direct calculation, their zero supplement serum 25(OH)D concentration was 18.0 (±9.5) ng/ml, significantly lower than for N-H Whites, for whomY0=33.4 (±26.4) ng/ml (p<0.001). The ‘Other’ ethnicity category (largely Eastern Asiatics; n=230) had sufficient data to permit fitting to Equation 1. Its parameters did not differ appreciably from those of the N-H White group, except for the Y0 estimate, which was 26.6 (±23.7) ng/ml, also significantly lower than the Y0 parameter estimate for N-H Whites (p<0.001). These differences are consistent with expectations based on skin pigmentation.
Because obesity is recognized to be associated with low vitamin D status, the residuals from the above curve fit were regressed against body weight and demonstrated the expected inverse relationship (r2=0.03). While statistically significant (p<0.01), this relation failed to account for most of the between-participant variance.
A question frequently asked by clinicians is how much of an increase in serum 25(OH)D should be expected for a given additional oral dose of vitamin D. Figure 3 provides an answer by plotting the first derivative of the equation in Figure 2 at various starting values. For example, at a starting value of 10 ng/ml, the mean increment that would be expected to be produced by an additional 1,000 IU/d is 11 ng/ml, whereas at 30 ng/ml it is 8 ng/ml, and at 50 ng/ml, only 5 ng/ml. Above a starting value of 90 ng/ml, the response is nearly flat at about 1.6 ng/ml/1,000 IU/d.
Because no serum 25(OH)D method has been specifically calibrated against standards above 100 ng/ml, the accuracy of the 25(OH)D values was assessed by superimposing the regression line from Figure 2 on previously published data (8) relating high-dose vitamin D intake to serum 25(OH)D. The results are shown as Figure 4. It is immediately apparent that the regression line from the blood spot method used in the present study superimposes on the data points previously published by Vieth (8), at least out to 100,000 IU/d, which is as far as the GRH data extend.
Discussion
To the Authors’ knowledge this is the first analysis of the relation of vitamin D status to voluntary vitamin D supplementation as practiced in the community. The community base, the size of the sample, and the completeness of the pertinent data are strengths. Weaknesses include the fact that no single vitamin D product was used, the products themselves were not evaluated for exact vitamin D content and the doses are self-reported. Additionally, the data are cross-sectional and cannot give a true picture of individual responses to dose changes. Nevertheless, several features of the current findings indicate that these limitations do not preclude drawing useful conclusions from these data.
As noted above, the fit derived from the total data set superimposes on the high-dose data assembled by Vieth (8). Additionally, the general shape of the curve (exponential at low intakes and linear at high) is precisely mirrored in an earlier publication by Heaney et al. (5), relating the serum concentrations of 25(OH)D and cholecalciferol, in which the inflection point between the linear and exponential components occurred at a serum 25(OH)D concentration of ~35 ng/ml, corresponding to a serum vitamin D concentration of ~4 ng/ml. These values are very similar to the pertinent parameters of the equation used here to describe the GRH data set. Both of these agreements among studies support the overall validity of the data in the present report.
The 95% probability bands in Figure 2 provide useful information on the dosages required to ensure that a specified fraction of the population would have 25(OH)D concentrations above any given level. Such inferences are not affected by the cross-sectional character of the data. The points where that lower band crosses 30, 40, and 50 ng/ml (75, 100, and 125 nmol/l) are the supplemental intake values that ensure that 97.5% of the population would be above the specified serum 25(OH)D concentrations concerned. These are, respectively, 6,100, 9,600, and 14,100 IU/d for this population. Observed mean (SD) 25(OH)D concentrations at these intakes are, respectively 64.6 (±18), 75.1 (±18), and 85.2 (±18) ng/ml. Given that the average, non-supplemental intake in this cohort was estimated to be ~3,300 IU/d, the total intake from a vitamin D-deprived basal state which would be required to ensure that all but 2.5% of the population would reach the specified serum 25(OH)D levels would be 9,400, 12,900, and 17,400 IU/d. Although an order of magnitude higher than currently recommended oral intakes (9), these calculated daily intakes are of the same magnitude as produced by a single, minimal erythemal dose of UV-B radiation, such as would be obtained during a few minutes of solar UVB exposure near noon in midsummer, assuming nearly complete skin exposure (10).
Although this data set provides no information with respect to serum or urine calcium values in these individuals, at the same time it is clear that there were no clinical evidences of toxicity. Indeed, since virtually all of the values, at whatever dose, were associated with 25(OH)D values below 200 ng/ml [and no doses below 50,000 IU/d produced serum 25(OH) D values above 200 ng/ml], the absence of apparent toxicity is not surprising. The very slow rise in serum 25(OH)D concentration for each 1,000 IU increment at serum values above 80-100 ng/ml (Figure 3) is firm expression of the general safety of even relatively high doses.
A prominent feature of this cohort is that it is self-selected for health consciousness. Hence, in terms of dosing choices, this cohort cannot be considered representative of the general population. Accordingly, given this cohort’s likely high degree of adherence to supplementation, the achieved vitamin D status values are almost certainly higher than would be expected in less-motivated members of the general public.
Finally, and as an incidental observation, these data suggest a possible insight into the pathogenesis of toxicity. It is suggested that such an outcome requires two conditions: (i) high dose and (ii) high individual responsiveness to any given dose. As Ilahi et al. (6) reported previously, values for Cmax following a single dose of 100,000 IU spanned a six-fold range from 4.9 ng/ml to 30.8 ng/ml. Had that dosing been continued (as in the high-dose members of the GRH cohort), a person with a 30.8 ng/ml increase would likely have exceeded a serum 25(OH)D concentration of 200 ng/ml, whereas a person at the low end of the range for Cmax, would not have.
Acknowledgements
Participant recruitment and data management for this study was provided by GrassrootsHealth. The Authors wish to thank Carole Baggerly, Director of GrassrootsHealth for her invaluable assistance and encouragement and the participants who provided the funding and the information for this study.
References
1.Nutrition Business Journal; 2010 Supplement Business Report, Sept. 28, 2010.
2.Garland CF, Gorham ED, Mohr SB and Garland FC: Vitamin D for cancer prevention: global perspective. Ann Epidemiol 19: 468-483, 2009.
3.Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, Newmark H, Holick MF, and Garland FC: Vitamin D and prevention of breast cancer: Pooled analysis. J Steroid Biochem Molec Biol 103: 708-711, 2007.
4.Eyles D, Anderson C, Ko P, Jones A, Thomas A, Burne T, Mortensen PB, Nørgaard-Pedersen B, Hougaard DM and McGrath J: A sensitive LC/MS/MS assay of 25OH vitamin D(3) and 25OH vitamin D(2) in dried blood spots. Clin Chim Acta 403: 145-151, 2009.
5.Heaney RP, Armas LAG, Shary JR, Bell NH, Binkley N and Hollis BW: 25-Hydroxylation of vitamin D3: relation to circulating vitamin D3 under varying input conditions. Am J Clin Nutr 87: 1730-1737, 2008.
6.Ilahi M, Armas LAG and Heaney RP: The pharmacokinetics of a single large dose of vitamin D3. Am J Clin Nutr 87: 688-691, 2008.
7.Hathcock JN, Shao A, Vieth R and Heaney RP: Risk assessment for vitamin D. Am J Clin Nutr 85: 6-18, 2007. 8 Vieth R: Vitamin D and cancer mini-symposium: the risk of additional vitamin D. Ann Epidemiol 19: 441-445, 2009.
8.Vieth R: Vitamin D and cancer mini-symposium: the risk of additional vitamin D. Ann Epidemiol 19: 441-445, 2009.
9.IOM (Institute of Medicine). 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press.
10.Webb AR and Holick MF: The role of sunlight in the cutaneous production of vitamin D3. Ann Rev Nutr 8: 375-399, 1988.
Received December 22, 2010
Revised January 18, 2011
Accepted January 19, 2011
1University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, U.S.A.;
2GrassrootsHealth, P.O. Box 234208, Encinitas, CA 92023, U.S.A.;
3Creighton University, 2500 California Plaza, Omaha, NE 68178, U.S.A.
Anticancer Research
Printable Download (PDF)
Paternal age related schizophrenia (PARS): Latent subgroups detected by k-means clustering analysis.
Schizophr Res. 2011 Feb 25. [Epub ahead of print]
Paternal age related schizophrenia (PARS): Latent subgroups detected by k-means clustering analysis.
Lee H, Malaspina D, Ahn H, Perrin M, Opler MG, Kleinhaus K, Harlap S, Goetz R, Antonius D.
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA.
Abstract
BACKGROUND: Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia.
METHODS: We studied PARS (operationally defined as not having any family history of schizophrenia among first and second-degree relatives and fathers' age at birth ≥35years) in a series of schizophrenia cases recruited from a research unit. Data were available on demographic variables, symptoms (Positive and Negative Syndrome Scale; PANSS), cognitive tests (Wechsler Adult Intelligence Scale-Revised; WAIS-R) and olfaction (University of Pennsylvania Smell Identification Test; UPSIT). We conducted a series of k-means clustering analyses to identify clusters of cases containing high concentrations of PARS.
RESULTS: Two analyses generated clusters with high concentrations of PARS cases. The first analysis (N=136; PARS=34) revealed a cluster containing 83% PARS cases, in which the patients showed a significant discrepancy between verbal and performance intelligence. The mean paternal and maternal ages were 41 and 33, respectively. The second analysis (N=123; PARS=30) revealed a cluster containing 71% PARS cases, of which 93% were females; the mean age of onset of psychosis, at 17.2, was significantly early.
CONCLUSIONS: These results strengthen the evidence that PARS cases differ from other patients with schizophrenia. Hypothesis-generating findings suggest that features of PARS may include a discrepancy between verbal and performance intelligence, and in females, an early age of onset. These findings provide a rationale for separating these phenotypes from others in future clinical, genetic and pathophysiologic studies of schizophrenia and in considering responses to treatment.
Copyright © 2011 Elsevier B.V. All rights reserved.
PMID: 21353765 [PubMed - as supplied by publisher]
Paternal age related schizophrenia (PARS): Latent subgroups detected by k-means clustering analysis.
Lee H, Malaspina D, Ahn H, Perrin M, Opler MG, Kleinhaus K, Harlap S, Goetz R, Antonius D.
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA.
Abstract
BACKGROUND: Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia.
METHODS: We studied PARS (operationally defined as not having any family history of schizophrenia among first and second-degree relatives and fathers' age at birth ≥35years) in a series of schizophrenia cases recruited from a research unit. Data were available on demographic variables, symptoms (Positive and Negative Syndrome Scale; PANSS), cognitive tests (Wechsler Adult Intelligence Scale-Revised; WAIS-R) and olfaction (University of Pennsylvania Smell Identification Test; UPSIT). We conducted a series of k-means clustering analyses to identify clusters of cases containing high concentrations of PARS.
RESULTS: Two analyses generated clusters with high concentrations of PARS cases. The first analysis (N=136; PARS=34) revealed a cluster containing 83% PARS cases, in which the patients showed a significant discrepancy between verbal and performance intelligence. The mean paternal and maternal ages were 41 and 33, respectively. The second analysis (N=123; PARS=30) revealed a cluster containing 71% PARS cases, of which 93% were females; the mean age of onset of psychosis, at 17.2, was significantly early.
CONCLUSIONS: These results strengthen the evidence that PARS cases differ from other patients with schizophrenia. Hypothesis-generating findings suggest that features of PARS may include a discrepancy between verbal and performance intelligence, and in females, an early age of onset. These findings provide a rationale for separating these phenotypes from others in future clinical, genetic and pathophysiologic studies of schizophrenia and in considering responses to treatment.
Copyright © 2011 Elsevier B.V. All rights reserved.
PMID: 21353765 [PubMed - as supplied by publisher]
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