Magnesium and Insulin Sensitivity

From a paper based on US NHANES nutrition and health survey data (1):

During 1999–2000, the diet of a large proportion of the U.S. population did not contain adequate magnesium... Furthermore, racial or ethnic differences in magnesium persist and may contribute to some health disparities.... Because magnesium intake is low among many people in the United States and inadequate magnesium status is associated with increased risk of acute and chronic conditions, an urgent need exists to perform a current survey to assess the physiologic status of magnesium in the U.S. population.

Magnesium is an essential mineral that's slowly disappearing from the modern diet, as industrial agriculture and industrial food processing increasingly dominate our food choices. One of the many things it's necessary for in mammals is proper insulin sensitivity and glucose control. A loss of glucose control due to insulin resistance can eventually lead to diabetes and all its complications.

Magnesium status is associated with insulin sensitivity (2, 3), and a low magnesium intake predicts the development of type II diabetes in most studies (4, 5) but not all (6). Magnesium supplements largely prevent diabetes in a rat model* (7). Interestingly, excess blood glucose and insulin themselves seem to reduce magnesium status, possibly creating a vicious cycle.

In a 1993 trial, a low-magnesium diet reduced insulin sensitivity in healthy volunteers by 25% in just four weeks (8). It also increased urinary thromboxane concentration, a potential concern for cardiovascular health**.

At least three trials have shown that magnesium supplementation increases insulin sensitivity in insulin-resistant diabetics and non-diabetics (9, 10, 11). In some cases, the results were remarkable. In type II diabetics, 16 weeks of magnesium supplementation improved fasting glucose, calculated insulin sensitivity and HbA1c*** (12). HbA1c dropped by 22 percent.

In insulin resistant volunteers with low blood magnesium, magnesium supplementation for four months reduced estimated insulin resistance by 43 percent and decreased fasting insulin by 32 percent (13). This suggests to me that magnesium deficiency was probably one of the main reasons they were insulin resistant in the first place. But the study had another very interesting finding: magnesium improved the subjects' blood lipid profile remarkably. Total cholesterol decreased, LDL decreased, HDL increased and triglycerides decreased by a whopping 39 percent. The same thing had been reported in the medical literature decades earlier when doctors used magnesium injections to treat heart disease, and also in animals treated with magnesium. Magnesium supplementation also suppresses atherosclerosis (thickening and hardening of the arteries) in animal models, a fact that I may discuss in more detail at some point (14, 15).

In the previous study, participants were given 2.5 g magnesium chloride (MgCl2) per day. That's a bit more than the USDA recommended daily allowance (MgCl2 is mostly chloride by weight), in addition to what they were already getting from their diet. Most of a person's magnesium is in their bones, so correcting a deficiency by eating a nutritious diet may take a while.

Speaking of nutritious diets, how does one get magnesium? Good sources include halibut, leafy greens, chocolate and nuts. Bone broths are also an excellent source of highly absorbable magnesium. Whole grains and beans are also fairly good sources, while refined grains lack most of the magnesium in the whole grain. Organic foods, particularly artisanally produced foods from a farmer's market, are richer in magnesium because they grow on better soil and often use older varieties that are more nutritious.

The problem with seeds such as grains, beans and nuts is that they also contain phytic acid which prevents the absorption of magnesium and other minerals (16). Healthy non-industrial societies that relied on grains took great care in their preparation: they soaked them, often fermented them, and also frequently removed a portion of the bran before cooking (17). These steps all served to reduce the level of phytic acid and other anti-nutrients. I've posted a method for effectively reducing the amount of phytic acid in brown rice (18). Beans should ideally be soaked for 24 hours before cooking, preferably in warm water.

Industrial agriculture has systematically depleted our soil of many minerals, due to high-yield crop varieties and the fact that synthetic fertilizers only replace a few minerals. The mineral content of foods in the US, including magnesium, has dropped sharply in the last 50 years. The reason we need to use fertilizers in the first place is that we've broken the natural nutrient cycle in which minerals always return to the soil in the same place they were removed. In 21st century America, minerals are removed from the soil, pass through our toilets, and end up in the landfill or in waste water. This will continue until we find an acceptable way to return human feces and urine to agricultural soil, as many cultures do to this day****.

I believe that an adequate magnesium intake is critical for proper insulin sensitivity and overall health.


* Zucker rats that lack leptin signaling

** Thromboxane A2 is an omega-6 derived eicosanoid that potently constricts blood vessels and promotes blood clotting. It's interesting that magnesium has such a strong effect on it. It indicates that fatty acid balance is not the only major influence on eicosanoid production.

*** Glycated hemoglobin. A measure of the average blood glucose level over the past few weeks.

**** Anyone interested in further reading on this should look up The Humanure Handbook

Dissolve Away those Pesky Bones with Corn Oil

I just read an interesting paper from Gabriel Fernandes's group at the University of Texas. It's titled "High fat diet-induced animal model of age-associated obesity and osteoporosis". I was expecting this to be the usual "we fed mice industrial lard for 60% of calories and they got sick" paper, but I was pleasantly surprised. From the introduction:

CO [corn oil] is known to promote bone loss, obesity, impaired glucose tolerance, insulin resistance and thus represents a useful model for studying the early stages in the development of obesity, hyperglycemia, Type 2 diabetes [23] and osteoporosis. We have used omega-6 fatty acids enriched diet as a fat source which is commonly observed in today's Western diets basically responsible for the pathogenesis of many diseases [24].

Just 10% of the diet as corn oil (roughly 20% of calories), with no added omega-3, on top of an otherwise poor laboratory diet, caused:

• Obesity
• Osteoporosis
• The replacement of bone marrow with fat cells
  
• Diabetes
• Insulin resistance
  
• Generalized inflammation
• Elevated liver weight (possibly indicating fatty liver)
  

Hmm, some of these sound familiar... We can add them to the findings that omega-6 also promotes various types of cancer in rodents (1).

20% fat is less than the amount it typically takes to make a rodent this sick. This leads me to conclude that corn oil is particularly good at causing mouse versions of some of the most common facets of the "diseases of civilization". It's exceptionally high in omega-6 (linoleic acid) with virtually no omega-3.

Make sure to eat your heart-healthy corn oil! It's made in the USA, dirt cheap and it even lowers cholesterol!

Saturated Fat and Insulin Sensitivity

Insulin sensitivity is a measure of the tissue response to insulin. Typically, it refers to insulin's ability to cause tissues to absorb glucose from the blood. A loss of insulin sensitivity, also called insulin resistance, is a core part of the metabolic disorder that affects many people in industrial nations.

I don't know how many times I've seen the claim in journal articles and on the internet that saturated fat reduces insulin sensitivity. The idea is that saturated fat reduces the body's ability to handle glucose effectively, placing people on the road to diabetes, obesity and heart disease. Given the "selective citation disorder" that plagues the diet-health literature, perhaps this particular claim deserves a closer look.

The Evidence

I found a review article from 2008 that addressed this question (1). I like this review because it only includes high-quality trials that used reliable methods of determining insulin sensitivity*.

On to the meat of it. There were 5 studies in which non-diabetic people were fed diets rich in saturated fat, and compared with a group eating a diet rich in monounsaturated (like olive oil) or polyunsaturated (like corn oil) fat. They ranged in duration from one week to 3 months. Four of the five studies found that fat quality did not affect insulin sensitivity, including one of the 3-month studies.

The fifth study, which is the one that's nearly always cited in the diet-health literature, requires some discussion. This was the KANWU study (2). Over the course of three months, investigators fed 163 volunteers a diet rich in either saturated fat or monounsaturated fat.

The SAFA diet included butter and a table margarine containing a relatively high proportion of SAFAs. The MUFA diet included a spread and a margarine containing high proportions of oleic acid derived from high-oleic sunflower oil and negligible amounts of trans fatty acids and n-3 fatty acids and olive oil.

Yummy. After three months of these diets, there was no significant difference in insulin sensitivity between the saturated fat group and the monounsaturated fat group. Yes, you read that right. Even the study that's selectively cited as evidence that saturated fat causes insulin resistance found no significant difference between the diets. You might not get this by reading the misleading abstract. I'll be generous and acknowledge that the (small) difference was almost statistically significant (p = 0.053).

What the authors decided to focus on instead is the fact that insulin sensitivity declined slightly but significantly on the saturated fat diet compared with the pre-diet baseline. That's why this study is cited as evidence that saturated fat impairs insulin sensitivity. But anyone who has a basic science background will see where this reasoning is flawed (warning: nerd attack. skip the rest of the paragraph if you're not interested). You need a control group for comparison, to take into account normal fluctuations caused by such things as the season, eating mostly cafeteria food, and having a doctor hooking you up to machines. That control group was the group eating monounsaturated fat. The comparison between diet groups was the 'primary outcome', in statistics lingo. That's the comparison that matters, and it wasn't significant. To interpret the study otherwise is to ignore the basic conventions of statistics, which the authors were happy to do. There's a name for it: 'moving the goalpost'. The reviewers shouldn't have let this kind of shenanigans slide.

So we have five studies through 2008, none of which support the idea that saturated fat reduces insulin sensitivity in non-diabetics. Since the review paper was published, I know of one subsequent study that asked the same question (3). Susan J. van Dijk and colleagues fed volunteers with abdominal overweight (beer gut) a diet rich in either saturated fat or monounsaturated fat. I e-mailed the senior author and she said the saturated fat diet was "mostly butter". The specific fats used in the diets weren't mentioned anywhere in the paper, which is a major omission**. In any case, after 8 weeks, insulin sensitivity was virtually identical between the two groups. This study appeared well controlled and used the gold standard method for assessing insulin sensitivity, called the euglycemic-hyperinsulinemic clamp technique***.

The evidence from controlled trials is rather consistent that saturated fat has no appreciable effect on insulin sensitivity.

Why Are We so Focused on Saturated Fat?

Answer: because it's the nutrient everyone loves to hate. As an exercise in completeness, I'm going to mention three dietary factors that actually reduce insulin sensitivity, and get a lot less air time than saturated fat.

#1: Caffeine. That's right, controlled trials show that your favorite murky beverage reduces insulin sensitivity (4, 5). Is it actually relevant to real life? I doubt it. The doses used were large and the studies short-term.

#2: Magnesium deficiency. A low-magnesium diet reduced insulin sensitivity by 25% over the course of three weeks (6). I think this is probably relevant to long-term insulin sensitivity and overall health, although it would be good to have longer-term data. Magnesium deficiency is widespread in industrial nations, due to our over-reliance on refined foods such as sugar, white flour and oils.

#3: Sugar. Fructose reduces insulin sensitivity in humans, along with many other harmful effects (7).

As long as we continue to focus our energy on indicting saturated fat, it will continue distracting us from the real causes of disease.

* For the nerds: euglycemic-hyperinsulinemic clamp (the gold standard), insulin suppression test, or intravenous glucose tolerance test with Minimal Model. They didn't include studies that reported HOMA as their only measure, because it's not very accurate.

** There's this idea that pervades the diet-health literature that all saturated fats are roughly equivalent, all monounsaturated fats are equivalent, etc., therefore it doesn't matter what the source was. This is beyond absurd and reflects our cultural obsession with saturated fat. It really irks me that the reviewers didn't demand this information.

*** They did find that markers of inflammation in fat tissue were higher after the saturated fat diet.