Magnesium and Vitamin D Metabolism

Ted Hutchinson posted a link in the comments section of my last post, pointing to a page on the Vitamin D Council's website where Dr. John Cannell discusses cofactors required for proper vitamin D metabolism. It's actually the site's home page, highlighting how important he feels this matter is. In this case, 'cofactor' simply means another nutrient that's required for the efficient production and use of vitamin D. They include:

• Magnesium
• Zinc
• Vitamin K2
• Vitamin A
• Boron

And probably others we aren't yet aware of. On another page, Dr. Cannell links to two papers that review the critical interaction between magnesium status and vitamin D metabolism (1, 2). Here's a quote from the abstract of the second paper:

Magnesium... is essential for the normal function of the parathyroid glands, metabolism of vitamin D and adequate sensitivity of target tissues to [parathyroid hormone] and active vitamin D metabolites. Magnesium deficit is usually associated with hypoparathyroidism, low production of active vitamin D metabolites, in particular 1,25(OH)2 vitamin D3 and resistance to PTH and vitamin D. On the contrary, magnesium excess, similar to calcium, inhibits PTH secretion. Bone metabolism is impaired under positive as well as under negative magnesium balance.

Magnesium status is critical for normal vitamin D metabolism, insulin sensitivity, and overall health. Supplemental magnesium blocks atherosclerosis in multiple animal models (3, 4). Most Americans don't get enough magnesium (5).

The bottom line is that no nutrient acts in a vacuum. The effect of every part of one's diet and lifestyle is dependent on every other part. I often talk about single nutrients on this blog, but my core philosophy is that a proper diet focuses on Real Food, not nutrients. Tinkering with nutritional status using supplements is potentially problematic. Despite what some people might tell you, our understanding of nutrition and human health is currently rather crude-- so it's best to respect the accumulated wisdom of cultures that don't get the diseases we're trying to avoid.

Low Vitamin D: Cause or Result of Disease?

Don Matesz at Primal Wisdom put up a post a few days ago that I think is worth reading. It follows an e-mail discussion between us concerning a paper on magnesium restriction in rats (executive summary: moderate Mg restriction reduces the hormone form of vitamin D by half and promotes osteoporosis). In his post, Don cites several papers showing that vitamin D metabolism is influenced by more than just vitamin D intake from the diet and synthesis in the skin.

Celiac disease patients have low 25(OH)D3, the circulating storage form of vitamin D, which spontaneously corrects on a gluten-free diet. There are numerous suggestions in the medical literature that overweight and sickness cause low vitamin D, potentially confounding the interpretation of studies that find lower levels of illness among people with low vitamin D levels.

Don't get me wrong, I still think vitamin D is important in preventing disease. But it does lead me to question the idea that we should force down huge doses of supplemental vitamin D to get our 25(OH)D3 up to 60, 70 or even 80 ng/mL. When the dosage of supplemental D goes beyond what a tan Caucasian could conceivably make on a day at the beach (4,000 IU?), that's when I start becoming skeptical. Check out Don's post for more.

Personal Responsibility and Health: Who Should Pay For Your Cheeseburgers?

Last year one of my "friends" on Facebook posted a status that infuriated me. It said "Why should I pay for health care for people who can't stop eating cheeseburgers from McDonald's?" I'm never one to downplay the importance of individual health behaviors like diet and exercise. In the three years since I met my husband he has gone from eating "less than one" (his words) serving of fruits/vegetables a day to at least four or five a day. And I'm sure that was the result of my gentle "nudging" because I was concerned for his health. However, this oversimplification that all acute or chronic illnesses are caused by "overweight people eating McDonald's" is incredibly ignorant. We cannot have a discussion about facilitators and barriers to good health outcomes without considering a person's environment, economic status, profession, family, peers, attitudes, beliefs, knowledge, etc. The list goes on.

There was an interesting article in The New York Times this week, No Matter What, We Pay for Others' Bad Habits, that explores this very issue of personal responsibility. The story had legs on Facebook and Twitter, so I wanted to incorporate it into the blog. And because I follow such thoughtful and interesting people online, I thought I'd include one of their quotes to demonstrate my point above (I removed her name in case she isn't interested in being a blog celebrity):

• "The notion of personal responsibility becomes almost a moot point if we don't have an environment that supports our ability to responsibly make "the healthy choice". As the Institute of Medicine says, "It is unreasonable to expect that people will change their behavior easily when so many forces in the social, cultural, and physical environments conspire against such change".
  

Some thoughts:

• Perhaps the hourly worker would like to make it to his healthy/yearly check-up at the doctor. However, because his job doesn't offer sick time since he's part-time, he could be fired for missing work. Therefore, he decides to miss his appointment, flu shot, blood pressure check, etc....because his paycheck is more important to his family.
  

• Perhaps there are a large number of people in a lower socioeconomic bracket that eat McDonald's cheeseburgers (as my Facebook "friend" noted above)...but maybe that's because there are no Whole Foods or Trader Joe's Markets in their neighborhoods. And maybe they don't have a car to drive to one and/or the bus route doesn't pass those stores. And I know that those $1 burgers are a little less expensive than the $10 Rotisserie chicken that Whole Foods sells.

• Perhaps a parent wants their child to walk or ride their bike to school for exercise, but their neighborhood isn't safe. What if there are no side walks?
  

• And what about the impact of genetic and environmental factors in disease? A strong family history of cancer and heart disease cannot always be canceled out by eating vegetables and heading to the gym. And what about those people that are exposed to dangerous chemicals in their jobs. What about those that now suffer due to exposure to asbestos in their jobs before we knew how bad it was? Do they not deserve health care?
  

Again, I'm not downplaying personal responsibility. Patient compliance, healthy eating, and exercise are incredibly important. But let's not forget the complex systems which influence the health of individuals.

And to end with a Facebook "friend's" status that made me less angry: "I mean, seriously, if you're getting that angry cuz a fellow human being can now go to the 'effin doctor, you probably could use a few moments of self reflection..."

Talkin' Bout A Revolution...Jamie Oliver is much louder than a whisper!

So I just finished watching the premiere episode of "Jamie Oliver's Food Revolution". It is a new show on ABC that chronicles the journey of English chef Jamie Oliver as he tries to change the eating habits of residents in Huntington, West Virginia. Huntington was recently crowned the most unhealthy city in America.
It is obvious that Jamie has good intentions. He has left his family for several months to work on this project. He is especially concerned about the quality of food being served in the Huntington schools. However, my reaction to the first episode was "No, no, no! Stop what you're doing and talk to these people first!"

The most important part of any public health intervention is getting to know the community you are working with. The worst thing you can do is come in as an "outsider" and start barking orders. Some questions you should ask before getting started are: How does this community operate? Who makes the decisions? What are some of the barriers to serving fresh food in schools? What are the USDA guidelines? (which Jamie knows nothing about) Who are the individuals you want/need to get on board with your idea? How do the parents feel about their children's eating habits? How can you get their buy-in? What would be a realistic timeline for assessment/buy-in before trying to implement change?

Jamie went about this all backwards (which may very well have been to increase drama for a TV show, but it is still a great example of "what not to do"). His first day in town he was told he was viewed as an "outsider" by the trusted radio host...and still proceeded to go into the elementary school and lecture the chefs on how disgusting the food is (after only observing them for one day). And he's surprised he's getting push back on his efforts?! The only small victory he has is creating a partnership with "Pastor Steve" at the local Baptist church. Steve is a trusted leader in the community and knows the families and their challenges very well.

Too bad Jamie did not look to better models of this kind of community effort. Shape Up Somerville (Somerville, MA) began as a community based research study at Tufts University targeting 1^st through 3^rd graders in the Somerville Public Schools. Today there is Coordinator working on active and healthy living programs supported by the Health Department and a Taskforce that is a collaboration of over 11 initiatives and 25 stakeholders involved in working on various interventions across the city. Program components include a focus on the school lunch program, local restaurants, walk ability and safe routes to school, etc. (I'll give a shout out here to one of my public health heroes- Julia Bloom- who helped Tufts bring this model to more rural communities across the country!)

Shape Up Somerville represents a strong program that began with a strong base. The original program engaged key stakeholders and did not try to change the community without first finding out how it worked. The community and parent outreach were an obvious key to success...where that aspect is basically forgotten in the "Food Revolution". Jamie just seems like one man on a mission to change. At the end of the episode Jamie is visibly upset and says "they don't know why I'm here". Yeah- that's because you're an outsider lecturing them on how they should raise their kids!

I'll probably watch the second episode where he actually starts to engage the community...how about you?

Interesting Articles in the AJCN

I just received an RSS alert for the American Journal of Clinical Nutrition's latest articles. This upcoming issue is full of very interesting material:

1. Dr. Neil D. Barnard reviews food consumption patterns in the US from 1909 to 2007 (1). This is something I've written about a number of times. The most notable change is that industrial seed oil use has increased by more than 3-fold in the last 40 years, and even more in the last 100 although he doesn't provide those numbers. Butter and lard use declined sharply. Meat consumption is up, but the increase comes exclusively from poultry because we're eating the same amount of red meat we always have. Grain consumption is down, although it peaked around 1900 so it may not be a fair comparison with today:

In the late 1800s, wheat flours became more popular and available due to the introduction of new [high-gluten] wheat varieties, [low extraction] milling techniques, and transport methods, and during this time new breakfast cereals were introduced by John Harvey Kellogg, CW Post, and the Quaker Oats Company. Thereafter, however, per capita availability of flour and cereal products gradually dropped as increased prosperity, improved mechanization, and transport (eg, refrigerated railway cars) increased competition from other food groups. [Then they partially rebounded in the last 40 years]

2. Dr. S.C. Larsson published a paper showing that in Sweden, multivitamin use is associated with a slightly higher risk of breast cancer (2).

3. Soy protein and isoflavones, which have been proposed to do everything from increase bone mineral density to fight cancer, are slowly falling out of favor. Dr. Z.M. Liu and colleagues show that soy protein and/or isoflavone supplementation has no effect on insulin sensitivity or glucose tolerance in a 6 month trial (3). This follows a recent trial showing that isoflavones have no effect on bone mineral density.

4. Dr. Ines Birlouez-Aragon and colleagues showed that high-heat cooked (fried and sauteed) foods increase risk factors for diabetes and cardiovascular disease (insulin resistance, cholesterol, triglycerides), compared to low-heat cooked foods (steamed, stewed) in a one-month trial (4). The high-heat diet also reduced serum levels of long-chain omega-3 fatty acids and vitamins C and E.

5. Dr. Katharina Nimptsch and colleagues showed that higher menaquinone (vitamin K2) intake is associated with a lower cancer incidence and lower cancer mortality in Europeans (5). Most of their K2 came from cheese.

6. And finally, Dr. Zhaoping Li and colleagues showed that cooking meat with an herb and spice blend reduced the levels of oxidized fat during cooking, and reduced serum and urinary markers of lipid oxidation in people eating the meat (6).

New Review of Controlled Trials Replacing Saturated fat with Industrial Seed Oils

Readers Stanley and JBG just informed me of a new review paper by Dr. Dariush Mozaffarian and colleagues. Dr. Mozaffarian is one of the Harvard epidemiologists responsible for the Nurse's Health study. The authors claim that overall, the controlled trials show that replacing saturated fat with polyunsaturated fat from industrial seed oils, but not carbohydrate or monounsaturated fat (as in olive oil), slightly reduces the risk of having a heart attack:

These findings provide evidence that consuming PUFA in place of SFA reduces CHD events in RCTs. This suggests that rather than trying to lower PUFA consumption, a shift toward greater population PUFA consumption in place of SFA would significantly reduce rates of CHD.

Looking at the studies they included in their analysis (and at those they excluded), it looks like they did a nice job cherry picking. For example:

• They included the Finnish Mental Hospital trial, which is a terrible trial for a number of reasons. It wasn't randomized, properly controlled, or blinded*. Thus, it doesn't fit the authors' stated inclusion criteria, but they included it in their analysis anyway**. Besides, the magnitude of the result has never been replicated by better trials-- not even close.
• They included two trials that changed more than just the proportion of SFA to PUFA. For example, the Oslo Diet-heart trial replaced animal fat with seed oils, but also increased fruit, nut, vegetable and fish intake, while reducing trans fat margarine intake. The STARS trial increased both omega-6 and omega-3, reduced processed food intake, and increased fruit and vegetable intake. These obviously aren't controlled trials isolating the issue of dietary fat substitution. If you subtract the four inappropriate trials from their analysis, which is half the studies they analyzed, the significant result disappears. Those four just happened to show the largest reduction in heart attack mortality...
• They excluded the Rose et al. corn oil trial and the Sydney Diet-heart trial. Both found a large increase in total mortality from replacing animal fat with seed oils, and the Rose trial found a large increase in heart attack deaths (the Sydney trial reported total mortality but not CHD deaths).

The authors claim, based on their analysis, that replacing 5% of calories as saturated fat with polyunsaturated fat would reduce the risk of having a heart attack by 10%. Take a minute to think about the implications of that statement. For the average American, that means cutting saturated fat nearly in half to 6% of energy, which is a challenge if you want to eat a normal diet. It also means nearly doubling PUFA intake, which will come mostly from seed oils if you follow the authors' advice.

So basically, even if the authors' conclusion were correct, you overhaul your whole diet and replace natural foods with industrial foods, and...? You reduce your 10-year risk of having a heart attack from 10 percent to 9 percent. Without affecting your overall risk of dying. The paper states that the interventions didn't affect overall mortality.


* Not even single blinded.  Autopsies were not conducted in a blinded manner. Physicians knew which hospital the cadavers came from, because autopsies were done on-site. There is some confusion about this point because the second paper states that physicians interpreted the autopsy reports in a blinded manner. But that doesn't make it blinded, since the autopsies weren't blinded. The patients were also not blinded, though this is hard to accomplish with a study like this.

** They refer to it as "cluster randomized", which I feel is a misuse of that term.  The investigators definitely didn't randomize the individual patients: whichever hospital a person was being treated in, that's the food he/she ate. There were only two hospitals, so "cluster randomization" in this case would just refer to deciding which hospital got the intervention first. I don't think this counts as cluster randomization.  An example of cluster randomization would be if you had 10 hospitals, and you randomized which hospital received which treatment first.  It's analogous to individual randomization but on a group scale.

Fatty Liver: It's not Just for Grown-ups Anymore

The epidemic of non-alcoholic fatty liver disease (NAFLD) is one of my favorite topics on this blog, due to the liver's role as the body's metabolic "grand central station", as Dr. Philip Wood puts it. The liver plays a critical part in the regulation of sugar, insulin, and lipid levels in the blood. Many of the routine blood tests administered in the doctor's office (blood glucose, cholesterol, etc.) partially reflect liver function.

NAFLD is an excessive accumulation of fat in the liver that impairs its function and can lead to severe liver inflammation (NASH), and in a small percentage of people, liver cancer. An estimated 20-30% of people in industrial nations suffer from NAFLD, a shockingly high prevalence (1).

I previously posted on dietary factors I believe are involved in NAFLD. In rodents, feeding a large amount of sugar or industrial seed oils (corn oil, etc.) promotes NAFLD, whereas fats such as butter and coconut oil do not (2). In human infants, enteric feeding with industrial seed oils causes severe liver damage, whereas the same amount of fat from fish oil doesn't, and can even reverse the damage done by seed oils (3). [2013 update: obesity is probably the main contributor to NAFLD.  Obesity is associated with ectopic fat deposition in a number of organs, including the liver]

So basically, I think excessive sugar and industrial oils could be involved NAFLD, and if you look at diet trends in the US over the last 40 years, they're consistent with the idea.

I recently came across a study that examined the diet of Canadian children with NAFLD (6). The children had a high sugar intake, a typical (i.e., high) omega-6 intake, and a low omega-3 intake. The authors claimed that the children also had a high saturated fat intake, but at 10.5% of calories, they were almost eating to the American Heart Association's "Step I" diet recommendations**! Total fat intake was also low.

High sugar consumption was associated with a larger waist circumference, insulin resistance, lower adiponectin and elevated markers of inflammation. High omega-6 intake was associated with markers of inflammation. Low omega-3 intake was associated with insulin resistance and elevated liver enzymes. Saturated fat intake presumably had no relation to any of these markers, since they didn't mention it in the text.

These children with NAFLD, who were all insulin resistant and mostly obese, had diets high in omega-6, high in sugar, and low in omega-3. This is consistent with the idea that these three factors, which have all been moving in the wrong direction in the last 40 years, contribute to NAFLD.


* Fatty liver was assessed by liver enzymes, admittedly not a perfect test. However, elevated liver enzymes do correlate fairly well with NAFLD.

** Steps I and II were replaced by new diet advice in 2000. The AHA now recommends keeping saturated fat below 7% of calories.  However, the new recommendations focus mostly on eating real food rather than avoiding saturated fat and cholesterol.