Marc Joseph Nutrition - Blog

In a review study published in the journal Thrombosis and Hemostasis, researchers note that vitamin K deficiency may be much more common than previously thought.

A primary action of vitamin K in the body is to help in a chemical reaction called carboxylation. Potential vitamin K deficiencies can be identified by measuring in the body the level of under-carboxylated compounds, such as osteocalcin and matrix Gla protein (MGP), both of which are involved in the maintenance of bone structure.

The scientists note that there is a substantial amount of incompletely metabolized osteocalcin and MGP in many otherwise apparently healthy individuals, which suggests that the majority of these people may be subclinically deficient in vitamin K.

Results Not Surprising

The findings aren’t too surprising, given that the primary dietary sources of vitamin K are:

• Green, leafy vegetables - spinach, kale, chard, lettuce
• Broccoli
• Parsley

These aren’t foods that most people eat regularly in adequate amounts (e.g., a cup per day). And, the biological half-life of vitamin K is relatively short — a few days. That means if you’re not regularly consuming vitamin K, you may become deficient.

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Last month, I wrote a post questioning the conclusions of a poorly designed National Cancer Institute study that suggested taking “excessive” multivitamins could increase your risk for prostate cancer.

More recently, the Life Extension Foundation (LEF) put together an even more damning and detailed critique of the study’s results that raises other excellent points worth considering:

1. Study participants may have been mis-classified.

As mentioned in my earlier post, the study used self-reported food frequency questionnaires (FFQs) to ask study participants about prior supplement usage. FFQs are subject to significant error, as participants may over- or under-report supplement use.

As LEF notes:

Questionnaire-based information collection is limited in accuracy to the memory recall of the study subjects. The majority of people cannot recall what they ate for breakfast one week ago, or which shirt they wore to work two weeks ago, or how many gallons of gas they purchased during their last trip to the gas station, never mind specific doses and frequency of use of a myriad of dietary supplements months or years ago.

But it gets better when we learn what the researchers actually did in this case:

In this government-funded study bashing multivitamins, the researchers had the audacity to place each subject who stated they did not know how much vitamin E they took into the 400 IU a day category. This means when the results where tabulated to see if multivitamin use was associated with prostate cancer risk, men who may or may not have taken any vitamin E were deemed to have taken 400 IU a day.

Men who reported taking even one multivitamin supplement a month were recorded as taking a multivitamin every single day. This meant that when the data was tabulated, those who may have taken as few as twelve multivitamin supplements a year where considered to have taken a multivitamin each day.

If one were designing a study to make it impossible to conclude anything meaningful from the results, this would be a good way to do it.

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A few weeks ago, I wrote about the cancer-vitamin D link and highlighted an excerpt from an article that hinted at the pending release of a study with extremely promising findings:

[P]erhaps the biggest bombshell about vitamin D’s effects is about to go off. In June, U.S. researchers will announce the first direct link between cancer prevention and the sunshine vitamin. Their results are nothing short of astounding.

A four-year clinical trial involving 1,200 women found those taking the vitamin had about a 60-percent reduction in cancer incidence, compared with those who didn’t take it, a drop so large — twice the impact on cancer attributed to smoking — it almost looks like a typographical error.

Well, the paper has just been published in the American Journal of Clinical Nutrition. And the results are nothing short of spectacular.

In the double-blind, placebo-controlled study, researchers randomly assigned postmenopausal women (age >55) to receive either 1400-1500 mg of calcium alone (Ca), the calcium plus 1100 IU vitamin D3 (Ca+D), or a placebo.

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And on it goes. The latest salvo against nutritional supplements is a new study published in the Journal of the National Cancer Institute that suggests men taking “excessive” multivitamins are at increased risk for advanced and fatal prostate cancers.

Specifically, researchers found that men who took multivitamins more than 7 times a week had a 32% and 98% greater risk of developing advanced and fatal prostate cancers, respectively.

Advanced prostate cancer is certainly serious condition, but let us count the ways why the results of this study should not be of significant concern:

- No association was observed between multivitamin use and overall prostate cancer risk.

- No association was observed between multivitamin use and localized prostate cancer risk. With regular screening (prostate specific antigen - PSA & digital rectal exam - DRE) now much more common, the vast majority of prostate cancers are caught at a localized, early stage. Many treatment options are available and prognoses are good in such cases. In fact, most older men, and many younger men, have cancerous cells in their prostates. Yet, since the cancer is often slow growing, those affected individuals identified through screening often go on to die years later from another condition.

(Just to be clear, I’m not trivializing prostate cancer and its potential effects. It is the most common form of cancer affecting men, and more aggressive forms of prostate cancer, although infrequent, can be deadly. Regular screening and accurate diagnosis are important.)

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Two recent studies in the Archives of Ophthalmology suggest that individuals with greater consumption of omega-3 fatty acids and higher vitamin D levels may be at lower risk for developing age-related macular degeneration (AMD), the most common cause of blindness for people over age 50.

There are two primary forms of AMD, the dry form, which is caused by loss of cells in the epithelial layer in the retina, and the wet (or neovascular) form, which is caused by abnormal blood vessel growth in the retina.

Omega-3

In the first study, researchers divided participants into five groups (quintiles) based on total omega-3 fat intake and found that the individuals in the top quintile were 39% less likely to develop wet AMD than people in the lowest quintile of intake. Scientists also looked at a specific omega-3 fatty acid (DHA - docosahexanoic acid), which is found in high concentration in the retina, and observed a 46% reduction in AMD risk when comparing the highest and lowest quintile of intake.

Additionally, fish intake positively correlated with reduced wet AMD risk in the study, but as discussed earlier, I would be reluctant to eat high levels of fish given the potential risk for toxin exposure. Vision disturbances are common in mercury poisoning cases. Contaminant-tested fish oil supplements are much preferred as a safer omega-3 source.

Interestingly, researchers found that high consumption of arachidonic acid (AA) was associated with a 54% increase in wet AMD risk. AA is an omega-6 fatty acid found in high quantities in red meat, dairy, and egg yolks, as well as metabolized from vegetable oils, such as corn and soybean oils commonly used in processed, packaged, and restaurant-prepared foods. This finding once again suggests that it is important to not only ensure adequate omega-3 intake, but also to moderate omega-6 intake, in order to manage inflammation. I addressed this topic in an earlier post.

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Excellent article in last week’s Toronto Globe and Mail discussing vitamin D. Covers a lot of ground, including a preview of a forthcoming study with amazing findings:

[P]erhaps the biggest bombshell about vitamin D’s effects is about to go off. In June, U.S. researchers will announce the first direct link between cancer prevention and the sunshine vitamin. Their results are nothing short of astounding.

A four-year clinical trial involving 1,200 women found those taking the vitamin had about a 60-percent reduction in cancer incidence, compared with those who didn’t take it, a drop so large — twice the impact on cancer attributed to smoking — it almost looks like a typographical error.

There are some great segments in the article, e.g.:

Those studying the vitamin say the hide-from-sunlight advice has amounted to the health equivalent of a foolish poker trade. Anyone practising sun avoidance has traded the benefit of a reduced risk of skin cancer — which is easy to detect and treat and seldom fatal — for an increased risk of the scary, high-body-count cancers, such as breast, prostate and colon, that appear linked to vitamin D shortages.

The sun advice has been misguided information “of just breathtaking proportions,” said John Cannell, head of the Vitamin D Council, a non-profit, California-based organization.

“Fifteen hundred Americans die every year from [skin cancers]. Fifteen hundred Americans die every day from the serious cancers.”

The whole thing is really worth reading.

Not Just Cancer

Vitamin D has also been linked to many other conditions, including multiple sclerosis, type 1 diabetes, heart disease, stroke, autoimmune diseases, influenza (the flu), and, of course, osteoporosis. Not too surprising given that vitamin D is actually a hormone (i.e., a chemical produced in one area of the body with effects on cells and tissues elsewhere in the body).

The results of the study above could potentially have far-reaching implications:

One of the researchers who made the discovery, professor of medicine Robert Heaney of Creighton University in Nebraska, says vitamin D deficiency is showing up in so many illnesses besides cancer that nearly all disease figures in Canada and the U.S. will need to be re-evaluated. “We don’t really know what the status of chronic disease is in the North American population,” he said, “until we normalize vitamin D status.”

What You Can Do

The primary source for vitamin D is the sun hitting exposed skin. Foods contain little vitamin D. People who spend most of their time indoors (e.g., office-workers, elderly), always wear sunblock, and/or who live in northern latitudes where even mid-day sun is not strong enough to generate adequate vitamin D are at high risk for deficiency.

Best bets to ensure adequate vitamin D levels:

• Get your vitamin D level checked once per year, preferably at a time that it is likely to be low (e.g., winter). The correct test is 25-hydroxyvitamin D. Target a level of 45-50 ng/mL (110-125 nmol/mL). One day this test will be included as a standard part of annual checkups.
• If getting vitamin D through mid-day sun exposure, 10-15 minutes 3 to 4 days a week for fair skinned people is typically adequate. Darker skinned people may need twice as much time in the sun. The pigment in the skin acts as sun-screen. You do NOT want the skin to change color; that means you’ve gotten more exposure than you need.
• Supplement with 1000 IU vitamin D3 (cholecalciferol) per day as a baseline year-round. As noted above, vitamin D costs only pennies a day. Always take vitamin D supplements with a meal containing fat for best absorption.
• In the winter, or if you’re not getting regular mid-day sun 10-15 minutes 3 to 4 days a week, increase daily supplementation to 2000 IU per day.
• Note that even 2000 IU per day may not be sufficient to reach target levels. Some research suggests the body may use as much as 3000 to 5000 IU per day or more.

Again, your best first step is getting your vitamin D level tested to make sure the combination of sun exposure and supplementation that you’re getting/using is keeping your body’s level at the high-end of the normal range year-round. Don’t guess.

Related Links

Vitamin D Deficiency Common Among Pregnant Women, Newborns

Researchers Call for Increase in Vitamin D Levels

Higher Vitamin D Levels May Greatly Lower Breast, Colon Cancer Risk

Epidemic Influenza and Vitamin D

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Discover How Nutrition Can Make a Difference in Your Life …

Marc Joseph Nutrition

Methylation, the donation of methyl (CH3) molecules, is a primary mechanism by which genes in a cell’s DNA are turned off. Lack of methyl groups or removal of methyl groups (demethylation) causes genes to remain or become activated.

In a process called epigenetics, cells also use methylation to specialize later in development without relying upon the instructions contained in the cell’s DNA. This type of specialization is especially vulnerable to environmental factors, such as nutritional deficiencies and exposure to toxins.

In a recent study published in the journal Neuron, researchers suggest that this type of epigenetic methylation may be key in forming memories.

In their experiments, the researchers conditioned fearful memories in rats by giving the animals mild shocks when they were in a specific training chamber. The researchers could then test whether the rats remembered the conditioning by observing whether they froze when placed in the chamber.

Using drugs that inhibit methylation, the researchers showed that methylation was necessary for rats to form such memories. Particularly importantly, the researchers found that the level of methylation directly controlled the activity of genes known to either suppress or promote memory formation. The memory suppressor gene they studied is called protein phosphatase 1, and the memory-promoting gene is called reelin.

“To our knowledge, this study is the first to present evidence that DNA methylation, once thought to be a static process after cellular differentiation, is not only dynamically regulated in the adult nervous system but also plays an integral role in memory formation,” concluded Miller and Sweatt. They wrote that their findings indicate that DNA methylation has been co-opted by the central nervous system as a “crucial step” in regulating gene activity involved in memory formation.

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Last Fall, I posted on a study that looked at vitamin D deficiency among pregnant women in Northern Europe:

Vitamin D Deficiency During Pregnancy

And now, a new North American study has been released that both confirms and heightens the need for concern regarding vitamin D levels in both pregnant women and their newborns.

In this latest study published in the Journal of Nutrition, researchers looked at vitamin D levels in both black and white women and their newborns in Pittsburgh, PA. Over 90 percent of the women took prenatal vitamins during pregnancy.

What the researchers found was simply amazing:

• More than 83 percent of black women and 47 percent of white women had insufficient or deficient levels* of vitamin D at delivery.
• More than 92 percent of black newborns and 66 percent of white newborns had insufficient or deficient levels* of vitamin D at delivery.

* In this study, deficiency and insufficiency levels were defined as <37.5 nmol/L and 37.5 to 80 nmol/L, respectively. 80 nmol/L is recognized by most leading vitamin D researchers as a minimum level of sufficiency, with higher levels (e.g., 110 to 125 nmol/L) likely being more optimal.

Clearly, the current vitamin D intake recommendation for pregnant women (600 IU/day) is not adequate. Remember, nearly all of the mothers in this study were also taking prenatal supplements.

The results of this study give even more urgency to the call earlier this year for an increase in the vitamin D upper-limit (UL) recommendation.

Bottom line

Mothers and their newborns in Northern latitudes are at significant risk for vitamin D deficiency. Sunshine (UVB rays) hitting the skin is the primary source of vitamin D. And with many adults in sunnier climates diligently avoiding the sun and using high-number sunscreens, even mothers living in Southern latitudes are potentially at risk for deficiency.

As discussed here, adequate daily intake levels may be at least 2,000 IU/day, and possibly higher, for individuals not getting regular, limited sun exposure.

Ideally, you want to target a vitamin D (25-hydroxyvitamin D) blood level toward the high-end of the sufficiency range (45 to 50 ng/mL or 112 to 125 nmol/L).

Vitamin D isn’t just important for pregnant women and their children. It’s also key in helping to reduce the risk of:

• Several types of cancer (colon, breast, pancreatic, prostate, ovarian, etc.)
• Multiple sclerosis
• Influenza
• Nursing home admission
• And more …

Vitamin D is one nutrient in which you definitely don’t want to be deficient.

Over the course of the last couple of years, there have been numerous articles and reports in the mainstream press on the negative effects of taking supplements. The most recent subject of scorn are antioxdiant supplements, which, according to a study published in the Journal of the American Medical Association (JAMA), apparently increase our risk of death.

The analysis, which pooled data from 68 studies involving more than 232,000 people, found no evidence that taking beta carotene, Vitamin A or Vitamin E extends life span and, in fact, indicated that the supplements increase the likelihood of dying by about 5 percent. Vitamin C and selenium appeared to have no impact — either way — on longevity …

… “The message is: We shouldn’t be putting anything in our mouths until we know whether it works,” said Christian Gluud of the Copenhagen University Hospital in Denmark, who led the study. “It appears as if these substances may be harmful.”

The Whole Story?

As a meta-review analysis (essentially an analysis of the existing body of research in aggregate), a key factor determining this study’s outcome is the selection of the studies to include in the analysis. As the study’s abstract notes, the meta-review included all randomized studies examining antioxidants in primary and secondary prevention trials published prior to October 2005.

But the researchers didn’t stop there. They then …

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Last month, I had a post discussing the importance of ensuring adequate levels of both folic acid and vitamin B12 to help prevent cognitive decline:

Key Nutrients in Helping to Prevent Cognitive Decline

In a new study out this month in the American Journal of Clinical Nutrition, researchers evaluated 1779 Mexican Americans between the ages of 60 and 101, and found that those individuals with high homocysteine levels and low vitamin B12 levels were at significantly greater risk of developing dementia.

Specifically, study participants with high homocysteine levels had more than double (139%) the risk of developing dementia than individuals with normal homocysteine values. And, participants whose serum vitamin B12 levels were in the lowest third of those measured had more than 60 percent greater risk of dementia.

Vitamin B12 is used in the primary pathway conversion of homocysteine back to methionine in the methylation cycle. (Betaine, or tri-methyl-glycine, is used in the secondary pathway converting homocysteine to methionine.) Methylation reactions are fundamental to many cellular processes, including expression of genes and proteins. Without adequate vitamin B12 intake, absorption, and utilization, homocysteine levels rise and the methylation cycle is impaired.

Vitamin B12 is also critically important in the methylation reactions involved in the proper formation of myelin, the “insulation” that coats nerve cells and is necessary for proper communication between them.

An interesting note about this study is that the researchers found a significant negative relationship between vitamin B12 and dementia (low vitamin B12, high dementia risk) looking only at serum vitamin B12 levels. That’s certainly one measure of potential deficiency, but a more reliable approach would be to measure methylmalonic acid (MMA), which builds up when vitamin B12 is low and is a sensitive, early deficiency marker. Your best bet for assessing vitamin B12 deficiency is to look at serum vitamin B12, MMA, and homocysteine levels in aggregate, rather than just relying on one measure.

Vitamin deficiencies (e.g., vitamin B12, folate) may be involved in dementia and cognitive decline, but they are not the only potential causes. For more on other contributing factors, see here.