Say “sodium” in a medical context, and most people will reflexively think “hypertension,” not psoriasis.

But dermatologist Katrina Abuabara and her research team at the University of California San Francisco have amassed considerable evidence suggesting that salt may play a role in development of psoriasis and other inflammatory skin disorders.

Based on data from nearly 469,000 people in the UK Biobank, Dr. Abuabara and her colleagues found that high sodium levels—as estimated by urinary sodium excretion—raise the risk of having psoriasis. Each one-gram increase in sodium conferred an 18% increase in the odds of having this skin disease.

The study was published last month in the Journal of the European Academy of Dermatology and Venereology.

The UCSF researchers saw an even larger correlation in the US-based NHANES data set, though the number of subjects in the NHANES set was vastly smaller. Last year, the team also showed a similar correlation between sodium levels and atopic dermatitis.

“We thought the kidney did all the salt and water balancing. But it turns out that skin probably also plays an important role.”

“We’ve known for a long time that salt affects blood pressure, and cardiovascular risk, and that we should probably all eat less salt than we do. It should not be surprising that salt might affect other organ systems as well,” Dr. Abuabara told Holistic Primary Care.

Skin Stores Salt

The notion that sodium could play an etiologic role in skin disease might sound strange on first hearing. But it makes physiological sense for several reasons. For one, that the skin stores sodium—a lot of it. In fact, the largest amount of exchangeable sodium in the human body is stored in skin, she explained.

“It used to be that we thought the kidney did all the salt and water balancing. But it turns out that skin probably also plays an important role.”

She credits nephrologist Jens Titze with this discovery. Titze was involved in a study of Russian cosmonaut trainees who spent over 300 days in a space simulator, which enabled researchers to monitor everything they ate and drank, and to measure a host of biomarkers, including urinary sodium output.

“They realized that the equations for sodium intake and output didn’t quite add up, and that we are actually storing sodium somewhere in our bodies. Fast-forward, a decade of research later, it turns out that a lot of that is in the skin,” explained Dr. Abuabara.

Sodium & Inflammation

Signals coming from research on animal models for brain disorders like encephalitis and multiple sclerosis suggested that chronically high tissue sodium levels could lead to immune system dysregulation.

“There were studies looking at the role of sodium on Th17 pathways, which have relevance in psoriasis. There’s another more recent paper that looked at sodium and how it affected T-cells. Sodium can trigger some of the Th2 type cytokines that we see in atopic dermatitis.”

High tissue sodium levels modulate immune cell function, both by proinflammatory mechanisms involving M1 macrophages and TH17 cells, and also by abrogating anti-inflammatory responses. Elevated sodium levels inhibit macrophage differentiation and T regulatory cell (Treg) function. One study found skin sodium concentrations were correlated with inflammatory markers and IL-17+ γ𝛿 T cells in the blood of patients with psoriasis.

“So, thinking that we store a lot of sodium in our skin, and that, when it sticks around sodium may cause imbalances in the immune system which have relevance in skin diseases, I thought perhaps there’s a link,” Dr. Abuabara continued.

From an historical perspective, there is a definite pattern.  

“Diseases like atopic dermatitis have increased dramatically over the past 50 years, especially in industrialized, Westernized countries—and it’s true in Asia as well. And this is where we see higher levels of salt consumption. Perhaps it’s not coincidental,” Dr. Abuabara said.

Compelling Correlations

For their newest study, Abuabara and colleagues estimated sodium intake based on 24-hour urine sodium excretion data from 468,913 subjects in the UK Biobank database. These data were collected between 2006 and 2010. The people in the cohort had a mean age of 57, and represented various regions in England, Scotland, and Wales.

The salt estimates were all based on spot urine tests, which are relatively easy and inexpensive, but only reflect sodium levels at a specific point in time. To compensate for that limitation, the UCSF researchers applied the INTERSALT equation, a well-validated method for estimating sodium levels that takes into account age, BMI, sex, and kidney function. “You’re augmenting those single spot measurements based on other things you know about the subjects,” she explained.

Within the UK Biobank cohort, 14,321 people (3.1%) were diagnosed with psoriasis from 2006 to 2010, based on ICD-10 codes. These cases were more or less evenly divided between females and males, and the overwhelming majority (96.5%) of affected people were White.

Overall, there were no differences in estimated sodium intake between the subgroup with psoriasis and their non-psoriatic counterparts. However, when adjusted for age, sex, race, socioeconomic status, and education level, the data showed a striking pattern: each gram of daily sodium intake raised the odds ratio for psoriasis by 18% (OR 1.18, 95% CI: 1.14–1.21).

The UCSF team also saw some overlap between psoriasis and other salt-related disorders. For example, among people with hypertension, 3.7% had psoriasis, versus 2.7% among the non-hypertensive population.

“What we can say is that there seems to be an association, which is really interesting, and should drive more research.”

Similarly, psoriasis was present among 4.6% of those with chronic renal failure, versus 3% of those with normal kidney function. Among those with diabetes, 4.4% had psoriasis, versus 2.9% of the non-diabetic participants.  The study was authored by Aheli Chattopadhyay, MD, who worked in the Abuabara lab during her medical training at UCSF.

Abuabara’s team made a similar analysis of data from 2,393 subjects in the Center for Disease Control’s NHANES database. Of these, 62 (2.6%) had self-reported physician-diagnosed psoriasis, and another 63 (2.6%) had psoriasis diagnoses confirmed by direct examination.

Using the same method to estimate daily sodium intake, the UCSF group found that each additional gram of salt per day increased the odds of exam-confirmed psoriasis by 47% (OR: 1.47, 95% CI: 1.19-1.83). For self-reported psoriasis, the odds increased by 31% per additional estimated gram (OR: 1.31, 95% CI: 1.01-1.69).

Given that from a hypertension perspective, some people are more salt-sensitive than others, Abuabara and colleagues wondered if there might be certain sub-populations that have a similar sort of salt-sensitivity in the skin. It’s an intriguing concept. But when they looked the data, they found that the magnitude of the correlation between salt and psoriasis was more or less consistent across racial, ethnic, and age subgroups.

“Based on data to date, we don’t have a strong ‘smoking gun’ to suggest that this is most relevant for any particular sub-population.”

Is There a Causal Relationship?

Dr. Abuabara said she hesitates to speculate about why the apparent effect size was so different between the two databases, other than to say that the US NHANES cohort was far smaller, but much more racially and ethnically diverse than the UK Biobank. Further, the methods for assessing sodium differed between NHANES and UK Biobank.

She was also reluctant to draw any firm conclusions about a causal relationship between salt and psoriasis.

“What we can say is that there seems to be an association, which is really interesting, and should drive more research. To be clear, all we’ve shown in the population-based data is that there is an association between urine biomarkers of sodium, and psoriasis. We were not looking at psoriasis onset or severity. Based on the existing data, we can’t say which way it goes–whether psoriasis would cause more sodium in the urine, or vice versa. Or perhaps, having psoriasis, people eat differently. We’re not able to determine any of that based on the existing population data.”

That said, the psoriasis findings dovetail nicely with the UCSF group’s prior work on atopic dermatitis. Using data from a subset of 215,832 UK Biobank subjects, they made similar estimates of sodium excretion, and found that each one-gram increase raised the odds of having atopic dermatitis by 11% (adjusted odds ratio 1.11; 95% CI, 1.07-1.14). They also reported a pattern of increased severity of atopic dermatitis in association with higher sodium excretion levels.

Measurement Challenges

Though there’s good evidence that the skin does store salt, researchers are still working out the physiological mechanisms that regulate this process. It is not an easy thing to study, in part because there is no simple, clinically practical method for directly measuring salt levels in skin.

“If you anesthetize someone and take a biopsy, that messes up all the concentration gradients of ions,” Dr. Abuabara said.

Blood sodium measurements are of little use in this context. “Sodium levels are very changeable over a day. If we want to understand what people eat, we need to look at the sodium that comes out in their urine. It’s a better reflection. If you eat a lot of sodium one day, your body processes it, and the blood level will stay more or less constant. But the sodium in your urine will go up.”

She added that, “We don’t yet understand how all this relates to sodium in the skin. This is really a new field.”

New developments in MRI technology could make direct measurement much more practical, at least in research settings.

“Rather than a normal MRI machine, which is based on a magnet looking at the reflection of hydrogen atoms, you can get a special sodium coil and non-invasively measure the precise amount of sodium in someone’s skin,” said Dr. Abuabara. The UCSF department of dermatology has obtained grants to build one such machine, which are still few and far between.

“We’re starting studies to look more directly at what people consume, and how that relates to sodium in their skin, and how that, in turn, relates to skin disease. So, we’re really trying to put the pieces together. We’re also working with cardiologists and immunologists to understand how sodium specifically affects the immune profile in the skin and in the blood in relation to how much is salt stored.”

Protection Gone Awry?

Dr. Abuabara thinks cutaneous salt storage might be a physiological strategy for preventing water loss. A higher cutaneous salt concentration would form an ion gradient favorable to retention of water in the tissue.

Skin diseases like psoriasis and atopic dermatitis compromise skin barrier function, meaning that the skin is less able to retain water. In this situation, salt storage could be a physiological attempt to compensate for the impaired barrier function.

But, since salt can be pro-inflammatory, this defense mechanism easily becomes a destructive feedback loop in which the higher salt levels end up triggering more inflammation, tissue damage, and water loss. In a sense, this is a protective mechanism gone awry.

Though this model is still largely hypothetical, Dr. Abuabara pointed out that as people age their skin barrier function tends to decline. Concurrently, there’s an age-related increase in cutaneous sodium storage. The two phenomena may, in fact, be linked.

Clinical Concerns

We’ll see if future research gives credence to the notion that salt has an etiologic role in skin disease. For now, the best available research suggests four things:

• Skin is a major physiological store of sodium;
• Sodium in skin and other tissues can trigger inflammatory changes relevant to the pathogenesis of some cutaneous diseases;
• There are historical correlations between increased dietary sodium and prevalence of inflammatory skin diseases at the population level;
• Analysis of large population databases suggest correlations—though not causal relationships—between increased sodium and likelihood of psoriasis and atopic dermatitis at the individual level.

Low Salt: Good for Skin?

From a clinical perspective, the big question is whether reducing sodium intake could prevent, mitigate, or even reverse psoriasis, dermatitis, or other forms of skin disease.

Dr. Abuabara stressed that it is far too soon to answer that question.

“We don’t know what the impact of changing your dietary sodium would be. That said, we do know from public health research that most people eat far more sodium than is recommended. That guideline is to keep it under 2.3 grams (2300 mg) per day. But average salt intake in the US is far higher than that. We know that reducing sodium intake to the recommended levels has cardiovascular benefits. So, from a skin perspective, it probably can’t hurt to try it.”

Though she does not routinely push patients to cut salt from their diets, she said that she will review this research with patients who ask about how dietary factors might be affecting their skin. And she generally advises people to follow a healthy, plant-rich diet low in processed foods, to drink plenty of water, and to adhere to the established 2300 mg per day sodium guidelines.

“We don’t know what the impact of changing your dietary sodium would be. That said, we do know from public health research that most people eat far more sodium than is recommended. From a skin perspective, it probably can’t hurt to try it.”

Dr. Abuabara acknowledged that living with a chronic skin disease can be extremely frustrating and discouraging for patients, especially because symptoms often flare unpredictably, and triggers are seldom obvious. “People come in wanting suggestions on what do differently nutrition-wise, and unfortunately I don’t think we have a ton of evidence-based guidance.”

Salt intake is a modifiable factor. Though it is not always easy for people to reduce their salt intake, it is certainly a low-cost intervention with a lot of potential upsides for overall health, and no real downsides—unless someone is at risk for hyponatremia. If salt does prove to be an exacerbating factor in skin disease, affected patients might feel strong motivation to reduce their sodium consumption, especially if doing so leads to symptom relief and lesion resolution.

Future Directions

In the future, there might also be some pharmaceutical options for altering cutaneous salt levels. Dr. Abuabara said there’s some early stage work suggesting that the  Sodium Glucose Cotransporter (SGLT)-2 inhibitors sometimes used to treat diabetes, may reduce the amount of sodium in the skin.

“Typically, we don’t think about treating psoriasis or atopic dermatitis patients with those types of drugs. In the future, we would be interested in studying the impact of those drugs on skin disease. Perhaps they might complement some of our current treatment strategies.”

The discovery that salt is stored in the skin, and that it correlates with risk of skin diseases opens “a whole different paradigm” for both research and clinical care.

“So much research focuses on things that turn down the immune system. We have all kinds of wonderful new biologics and small molecules that can dramatically impact the lives of people with skin diseases like atopic dermatitis and psoriasis. But there’s far less research on what triggers the immunological change in the first place,” she said.

Salt may very well prove to be one of the most common triggers. It’s a subject that merits further study.

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