New research out of Stanford School of Medicine has revealed that insulin resistance can double a person’s risk of having major depressive disorder.

What’s more, that risk applies, regardless of whether you’ve ever suffered from depression before.

“If you’re insulin-resistant, your risk of developing major depressive disorder is double that of someone who’s not insulin-resistant, even if you’ve never experienced depression before,” said Natalie Rasgon, one of the researchers.

Insulin resistance: a major risk for major depressive disorder

insulin resistance

Studies suggest that at least 1 in 3 people is suffering from insulin resistance, and many don’t even know it. Unlike Type 1 diabetes, which arises from the pancreas’s inability to secrete insulin into the blood, insulin resistance is caused when the cells of the body become unable to respond to the hormone’s signalling.

Insulin tells our cells to process the glucose that’s in our blood, whether due to dietary intake, or its manufacture in the liver or both. Every cell in the body uses glucose as a fuel source. Receptors on the surface of every cell bind to insulin, which in turn signals the cell to ingest the precious energy source.

For a number of reasons, such as excessive caloric intake, a sedentary lifestyle, stress and even lack of sleep, these insulin receptors can fail to bind to insulin properly. This is what we mean by insulin resistance.

Over time, a person’s blood-sugar levels may become chronically high. Beyond a certain threshold, the diagnosis becomes Type 2 diabetes, a treatable but incurable condition that can lead to cardiovascular and cerebrovascular disorders, neuropathy, kidney disease, limb amputations and worse.

Links between insulin resistance and a number of different mental disorders have already been established. It’s been shown, for instance, that about 40% of patients suffering from mood disorders are insulin-resistant, according to Rasgon. We’ve already talked about the relationship between insulin resistance and testosterone levels, for instance, which have a strong effect on mood.

A short-term change to a paleo diet can significantly improve various health markers, including insulin sensitivity


paleo diet

These were the findings from a fascinating 2009 study we discussed in detail recently.

Nine non-obese but sedentary volunteers were selected for the study. The participants consumed their usual diet for 3 days, three ramp-up diets of increasing potassium and fiber for 7 days, then a paleo-type diet made up of lean meat, fruits, vegetables and nuts, and excluding ‘non-paleo’ foods, such as cereal grains, dairy or legumes, for 10 days. The diets were calorie-controlled to ensure no weight loss by daily weight.

The results were striking, across the board. In particular, there were significant reductions in blood pressure, significant increases in insulin-sensitivity markers and improvements to blood lipid profiles, especially triglycerides. Some of the results are presented in the table below.

The majority of such assessments have been based on cross-sectional studies, however, which are snapshots of populations at a single point in time. This makes it difficult to disentangle causes from effects. What is needed to do this are longitudinal studies, which follow subjects over a period of years or sometimes even decades.

The new insulin-depression study came out of the Netherlands Study of Depression and Anxiety, an ongoing longitudinal study monitoring more than 3,000 participants in close detail to learn about the causes and effects of depression.

The Stanford team analyzed data from 601 men and women who served as control subjects for the Netherlands study. At the time of their enrollment, none had ever had depression or anxiety. Their average age was 41 years.

The team measured three markers of insulin resistance: fasting blood glucose levels, waist circumference, and the ratio of circulating triglyceride levels to those of circulating high-density lipoprotein (HDL cholesterol).

They looked at the data to see if the subjects found to be insulin-resistant had a heightened nine-year risk of developing major depressive disorder. The answer was yes on all three counts: a moderate increase in insulin resistance, as measured by the triglyceride-to-HDL ratio, was linked to an 89% increase in the rate of new cases of major depressive disorder. Likewise, a 5-centimeter increase in abdominal fat was related to an 11% higher rate of depression, and an increase in fasting plasma glucose of 18 milligrams per deciliter of blood was associated with a 37% higher rate of depression.

Depression and obesity (and therefore insulin resistance) linked to vitamin D deficiency


See the source image

A recent study also showed that depression and obesity are linked to vitamin deficiency. Alarmingly, perhaps as much as 40% of the population is deficient.

While vitamin D can be consumed through dietary sources, most experts agree that it is difficult to reach the recommended daily amounts through diet alone. As a result, exposure to sunlight or supplementation is necessary to consume enough. 

With regard to sunlight exposure, the time of year, time of day, geographic latitude, cloud cover, pollution, skin melanin content (i.e. skin darkness), and sunscreen use all affect UV radiation exposure and vitamin D synthesis. For many, as a result, it will be necessary to supplement with vitamin D to ensure recommended daily amounts are met.

The issue of vitamin D deficiency has taken on an added significance during the current Coronavirus pandemic, in light of a recent Spanish study on the effects of oral administration of fortified vitamin D to Coronavirus patients

Some of the subjects were already insulin-resistant at the beginning of the study, so the researchers limited the next phase of their analysis to the roughly 400 subjects who, in addition to never having experienced major depression, also showed no sign of insulin resistance at the study’s onset.

During the first two years of the study, almost a quarter of these participants became insulin-resistant. The researchers compared this group’s likelihood of developing major depressive disorder in the next seven years with that of the participants who hadn’t yet become insulin-resistant at the two-year point.

Although the number of participants was not large enough to establish statistical significance for waist circumference and the triglyceride-to-HDL ratio, the results for fasting glucose were not only statistically significant but also clinically meaningful. Those who had developed prediabetes within the first two years of the study had 2.66 times the risk for major depression by the nine-year follow-up point, compared with those who had normal fasting-glucose test results at the two-year point.

The takeaway: insulin resistance is a strong risk factor not just for the serious problems we already know about, such as Type 2 diabetes, but also depression.

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