The Metabolic Syndrome Puzzle: The Vitamin D and MCAS Connection

Metabolic syndrome is an epidemic in the US and around the world. An estimated 36% of adults in the US suffer from metabolic syndrome, and that rate increases to almost 50% in those over the age of 60. Even more concerning is the startling increase in metabolic syndrome among young adults, jumping from 16% to 21% in recent surveys.

Obviously, something is not right.

At the same time as we are observing increasing rates of metabolic syndrome, a significant percentage of the population suffers from a deficiency of vitamin D. An estimated 41% of people have low serum levels (based on research that is over 10 years old, but more recent estimates of certain sub-groups of people bring that number to well over 50%), a number very close to those with metabolic syndrome. I don’t think this is a coincidence.

In the complex patient population I see, vitamin D deficiency, metabolic syndrome, and MCAS are quite common. All three conditions share common threads, and untangling those threads is part of the essential work of bodily repair and healing. As always, the goal is to dig down to the root of multi-system disease so the picture of how to restore health becomes clear.

The more research reveals about vitamin D, the more convinced I am that it is a significant contributor to the decline of health worldwide. And my experience in my own clinic confirms that we ignore vitamin D at our peril.

Let’s take a closer look at the relationship between vitamin D, metabolic syndrome, and MCAS.

What is Metabolic Syndrome?

First formally identified in 1998, metabolic syndrome is a cluster of conditions that feed off each other and increase the risk of serious disease. The criteria for diagnosis of metabolic syndrome include:

• Waist circumference > 94 cm (men) or > 80 cm (women) along with the presence of two or more of the following:

• Blood glucose greater than 5.6 mmol/L (100 mg/dl) or diagnosed diabetes

• HDL cholesterol < 1.0 mmol/L (40 mg/dl) in men, < 1.3 mmol/L (50 mg/dl) in women or drug treatment for low HDL-C

• Blood triglycerides > 1.7 mmol/L (150 mg/dl) or drug treatment for elevated triglycerides

• Blood pressure > 130/85 mmHg or drug treatment for hypertension

Another name for metabolic syndrome is insulin resistance syndrome, which is really the heart of the issue. Whether elevated triglycerides or high blood pressure, each of these conditions is strongly associated with baseline insulin resistance. Individuals with metabolic syndrome often also have type 2 diabetes or may develop type 2 diabetes in the future.

Metabolic syndrome is a clear warning from your body that all is not right. Having a high waist circumference means carrying excess adipose tissue in the belly region, which is more dangerous than carrying extra fat in other areas of the body. Add in two additional risk markers, and there is no doubt the body is in trouble.

Individuals with metabolic syndrome have a high risk of heart attack, stroke, and diabetes, some of today's most debilitating chronic health conditions. Treating and preventing metabolic syndrome is a high priority in my clinic, as reversing the course of present and future diseases must happen for a patient to feel better.

Causes of Metabolic Syndrome

Poor lifestyle habits lay the foundation for metabolic syndrome. Some of the things I look for when investigating metabolic health include:

• Overweight and obesity

• A sedentary lifestyle

• Dietary habits

• Insulin resistance

• Age - risk increases with age

• Genetics - ethnicity and family history play a role

Metabolic syndrome itself has no symptoms, and it is possible for someone to have metabolic syndrome and not know it. Conditions such as high blood pressure and elevated blood glucose, particularly elevated fasting glucose can fly under the radar in the early stages. Often no diagnosis is made until the patient's health has significantly deteriorated.

I never want to see this happen to my patients. When someone comes to my clinic, regardless of what they have already been diagnosed with, I’m always on the lookout for conditions that might be hidden or disguised as something else. A thorough investigation of risk factors for metabolic disease is nonnegotiable.

Another more recent consideration for metabolic syndrome is vitamin D status. While not traditionally linked, the interplay between vitamin D and many of the conditions that make up metabolic syndrome is just now becoming apparent.

The Link Between Metabolic Syndrome and Vitamin D

While metabolic syndrome is strongly associated with lifestyle habits, new information reveals low vitamin D may be a contributing factor. A recent study compared the vitamin D levels and insulin resistance markers of a group of otherwise healthy subjects. Here are the results in the author's own words:

“In this study, we observed consistent results in the general U.S. population, with a greater negative association between VitD3 and insulin resistance, particularly in the general U.S. population with a BMI of 24–28. According to data analysis, each 10-unit increase in VitD3 in this population was associated with a 20% reduction in the risk of insulin resistance, with an odds ratio and 95% CI of 0.8 (0.69, 0.93). “ Rongpeng Gong, Mingxiang Wang, Lei Yang et al. The association between the level of vitamin D3 and insulin resistance in the general adult population of the United States: A cross-sectional study based on the NHANES database, 11 March 2022, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-1410497/v1]

These findings provide a glimpse into vitamin D's role in healthy metabolic function. Individuals low in vitamin D are much more likely to be insulin resistant, with the highest risk among overweight individuals. But regardless of body weight, low vitamin D was associated with higher insulin resistance.

Whereas metabolic syndrome and insulin resistance have previously been considered conditions of the overweight (although we now understand that you can have both while being of normal weight and BMI), the revelation that low vitamin D is an independent risk factor gives us a new perspective.

We can leverage this information to improve insulin sensitivity not only for patients with metabolic syndrome but also for those at risk. I love to see quality research of this nature shed light on complex health conditions. Vitamin D is such a simple nutrient, yet its actions in our body are anything but.

Vitamin D, Inflammation, and Insulin Resistance

Vitamin D is critical for so much more than bone health. As the above study demonstrates, inadequate vitamin D has a ripple effect on many essential metabolic processes. The outcome can be severe.

Systemic inflammation is one pathway by which insulin resistance is caused or exacerbated. When the body is in a chronic state of inflammation, cells develop decreased sensitivity to insulin. Inflammatory cytokines interfere with the normal cascade of signals insulin sends when it binds with cell membranes. As a result, cells are unable to absorb glucose from the bloodstream, leading to elevated blood glucose levels and an increased risk of high blood pressure, hyperlipidemia, and type 2 diabetes. In essence, inflammation and metabolic syndrome go together.

Vitamin D has a strong influence on systemic inflammation. Adequate vitamin D is necessary to promote the production of anti-inflammatory cytokines. In addition, vitamin D reduces the release of pro-inflammatory cytokines, leading to a healthy check on inflammation in the body.

This link between vitamin D, inflammation, and insulin resistance is where MCAS comes into play.

MCAS. The Missing Piece of the Puzzle?

Mast cell activation syndrome (MCAS) doesn’t get a lot of attention for its role in metabolic syndrome, but if we connect the dots, you might be surprised by what emerges.

Inappropriately activated mast cells are among the biggest offenders in inflammatory states. In MCAS, mast cells release cytokines and other mediators that stimulate inflammation. Because MCAS is a chronic inflammatory condition, over time, inflammation damages tissues and organs and may contribute to the development of insulin resistance.

MCAS is a complex condition that often stems from more than one root cause. However, vitamin D deficiency is a common presentation in the patients I see with MCAS. This is no surprise as such a high proportion of the population is deficient in vitamin D. But the issue goes even deeper.

Vitamin D interacts with mast cells to make the mast cells less reactive and less likely to activate inappropriately. In the absence of the necessary vitamin D, mast cells lack this calming influence. The result is mast cells ripe for confusion and overreaction.

So, here we have a cluster of conditions that intertwine to form a complex picture with vitamin D at its center. Insufficient vitamin D can lead to inappropriately activated mast cells, leading to an inflammatory state that causes insulin resistance. As we know, insulin resistance is at the heart of metabolic syndrome. Whew.

It can be a lot to puzzle out! And there’s more to this story of the link between metabolic syndrome and MCAS (stay tuned for a future article on this). I have full sympathy for my patients who have struggled to find answers, sometimes for many years. Sorting through the research and understanding the cellular mechanisms is a full-time job.

That is why I have devoted my work to sifting through the data and partnering with complex patients to gain insight into all the pieces of the puzzle and how they fit together. In my many years of practice, it has become obvious that the pieces really do fit together! And once we can see what we are looking at, finding effective treatment becomes much simpler.

Where To Go from Here

Conventional treatment for metabolic syndrome typically focuses on medication management and often half-hearted encouragement of lifestyle changes.

I think we can do better.

When a patient comes to see me, either with a diagnosis of metabolic syndrome or with multiple risk factors, I always look deeper. Testing vitamin D levels is essential. In addition, evaluating mast cell function and inflammatory markers can shed further light on their condition.

Lifestyle changes are a cornerstone of successful management of any metabolic condition, but especially metabolic syndrome. While conventional medicine is not designed to walk patients through establishing healthy eating, activity, and stress management patterns, functional medicine is incomplete without it.

Treating the whole person requires a focus not just on the physiology of complex, multisystem disease but also on the environment from which it arises. In order to improve vitamin D levels and reverse metabolic syndrome, we have to look at all the influences from the life environment that may trigger mast cells or promote inflammation.

While vitamin D and MCAS are not the be-all end-all for everything that ails us, they are big pieces of the puzzle of many chronic health conditions. I’m committed to working with my patients to piece everything together and set them on the path to healing.

I would love to partner with you on your journey to better health. Contact me today and start the process of feeling better.