Can You Taste with Your Kidneys? Can You See with Your Blood Vessels?

I’ve only seen scurvy once. I was in training at Barnes Hospital in St. Louis, and a homeless man was admitted with weakness, muscle and bone pain, bleeding gums, and shortness of breath. It turned out that his diet consisted solely of hotdogs (no condiments) and Coke. It’s a good thing he came to tertiary care hospital, because scurvy is so rare now that many physicians wouldn’t even consider it in their diagnosis.

I will admit, though, that I’ve been watching a friend of my son for years, expecting to see my second case of scurvy. This friend only eats white rice. Well, he also eats white bread, and a few other things, but only bland things. I thought he would grow out of it but he still hasn’t, and he’s teenager.

I’ve been puzzled about his dietary habits, but I just read something that might explain this.

In The Medical Detective, Roueché describes a baker who suddenly developed a similar problem. The baker, named Rudy, had a perfectly normal sense of smell and taste until one day, he came down with a cold. Then suddenly, his smell and taste perception changed (and persisted). He couldn’t handle the smell in his pizza bakery any more. The ripe tomatoes smelled rotten. The entire kitchen smelled like burnt plastic. He could barely even stay in his house. Everything smelled like skunk. He had to sleep on his back because the smell of feathers in his pillow was overwhelming.

His sense of taste was affected even worse. Everything tasted terrible. Even mildly flavored food burned on his tongue. He had to subsist on cold milk, cold boiled potatoes, and peeled white grapes.

Rudy became an invalid. He couldn’t work. He couldn’t eat. He went from doctor to doctor. The doctors told him he was insane.

Fortunately, he chanced upon  Dr. Robert Henkin at the National Institutes of Health. Henkin happened to be a world expert in this disorder. He put a drop of hydrochloric acid on Rudy’s tongue. When Rudy couldn’t taste it, he knew right away what was afflicting Rudy.

Zinc deficiency.

He started Rudy on zinc and Rudy’s sense of smell and taste returned to normal in two weeks. Coincidence? Perhaps…not. When zinc was stopped, Rudy’s problem came back. And Dr. Henkin documented numerous cases of patients who had a similar response to zinc.

What was perhaps the most remarkable was that at NIH alone, he treated 55 people. NIH at the time had ten thousand employees. That meant that over a million people in the U.S. have this problem, most of whom are undiagnosed. This is corroborated by a study from 1998 that estimated 2.7 million people in the U.S. have a smell-related problem. Some of the patients have mild symptoms, but for many, the symptoms are devastating, even crippling.

Loss of, or alterations in taste, have never attracted as much attention from physicians (or even patients) compared to loss of hearing or sight. Dr. Henkin’s pioneering work, published in the 1970’s, has largely been forgotten. Even his finding that L-histidine can remove zinc from the body, resulting in taste changes, a finding that could be used for weight loss, has been forgotten. This is a shame, because when the field was hot, they were even finding that growth deficiency in children could be due to poor sense of taste, which in turn was due to zinc deficiency.

Henkin called this disorder hypogeusia, which means diminished taste, but modern term for this would be dysgeusia, or altered sense of taste.

Taste disorders are common under certain circumstances. Pregnant women or people who have a cold often have a change in taste–perhaps as result of a transient drop in zinc levels (zinc levels in the saliva, not blood, is what we’re concerned with here, since the zinc helps an enzyme called gustin work properly). Chemotherapy can affect the sense of taste, as can, ironically, cancer. Up to 10% of people who develop taste disorder are subsequently diagnosed with cancer. A lot of drugs, including penicillamine, can cause dysgeusia, often by binding to zinc and reducing overall zinc levels. Permanent changes in taste tend to happen after the flu, in people with hepatitis, or sometimes after surgery.

Smell and Mating

The problem is that smell and taste are still actually very important to us, the concrete jungle-dwelling urban species that we’ve become. Here is one very important role of smell:mate choice.

The evidence is fairly good, though not definitive, that women can smell, and are more attracted to, men whose immune system genes are different from her own. Much of the work has been done on HLA/MHC genes, which are responsible for immunity. People who have different MHC/HLA genes are resistant to different germs and parasites.

This study, Paternally inherited HLA alleles are associated with women’s choice of male odor, showed that women prefer t-shirts with odor from men who had moderately different HLA from their fathers. But not different from their mothers.

In this study, women also preferred the odor of men who were of a different MHC than themselves. Interestingly, their preferences flipped to the opposite when they were on oral contraceptives. In other words, when they’re fertile, they prefer mates who have a different immune gene background from them but when they’re infertile, they prefer to be around men of similar genetic background.

In animals, though, the data for this preference for males of different genetic background is very clear, across mice, rats, horses, fish, and birds.

This preference is consistent with the Red Queen Hypothesis, that postulates that the reason we have sexual reproduction is to increase the parasite resistance heterogeneity.

So if you can’t smell, then your choice of mate may be compromised. Who knew?

Smell Receptors in Our Kidneys?

But wait, that’s not all. It turns out that smell and taste receptors are not just in our nose and mouth. They’re all over the body.

In fact, it seems to be a general theme that receptors are repurposed for uses all over the body, because even light receptors are found in our blood vessels.  This is an interesting aside, so with your indulgence, I’m going to take a small detour in our story. Dr. Dan Berkowitz at Johns Hopkins University was studying blood vessel constriction in mice.

“But, after … [the] blood vessel analysis equipment was moved into a new space, the new room had motion detection lights, unlike the lab before. Dr. Sikka and the team noticed the tension in the blood vessels would decrease when the motion detection lights came on. Noticing this, the team decided to look further into this phenomenon.”

-from Johns Hopkins PR

Sikka and Berkowitz decided to explore a crazy idea, that blood vessels could “see” light. And shockingly, they found that the vessel constriction was controlled by opsin4, a light receptor thought only found in the eye, but actually expressed in blood vessels as well. This obviously opens up the exciting possibility that you might be able control hypertension and other blood vessel problems with light.

Further work buy another group even found the photoreceptor in the fat cells in our body. Light on a sunny day is sufficient to penetrate through the skin into the fat cells. When the fat cells sense light, they start lowering the amount of fat droplets in the cells. In effect, exposure to bright sunlight makes you thinner. This also fits with the hibernation theory of diabetes, and may partly explain why mammals, including humans, get fatter in the autumn/winter.

But back to our previous scheduled programming. It turns out that taste and smell receptors are all over our body. It was a shock when they were found in sperm, but then they were detected in the kidneys, brain, lung and a host of other organs. We have sour receptors in our spine, sweet receptors in our bladder and gut, bitter receptors in our sinuses, lungs, and brain, and so on. Some of these make sense. For example, when the lung senses a bitter compound, it tries to expel the compound. That makes sense, because many bitter compounds are poisonous.

What about the others? Well, here is the story of scent receptors in the brain

“In 2005 Jennifer Pluznick hypothesised that a gene known to play a role in a common form of kidney disease did so by acting as a master switch for other genes. Lab tests supported her theory; however, when she looked at which genes it acted on, she did a double take. Among them were several that encode scent receptors, the chemical sensors that allow us to identify smells.

“At first Pluznick didn’t believe her eyes. As far as we know, kidneys filter waste from our blood and get rid of it in urine. They are not sensory organs. “I wasn’t sure if we could believe the data,” she says. “It seemed really spurious.” Thinking there had to be a mistake, Pluznick, then a researcher at Yale School of Medicine, in New Haven, Connecticut, carried out another experiment. She soaked a slice of kidney in a fluid that would make scent-system proteins glow fluorescently under a microscope. When she peered down the eyepiece, it was lit up like a Christmas tree.”

– from BBC.com

It turns out that the kidney uses smell receptors to monitor the blood, and adjusts the filtration accordingly. If you knock out those receptors, the kidney doesn’t work properly.

Researchers are untangling some of the other roles. For example, the sour receptor appears to be important for regulating the pH in the CSF, the fluid that surrounds the brain and the spinal cord. It seems to regulate fat cells as well.

Subsequently, Pluznick has found that one smell receptor may allow our body to sense our gut microbiome, and control blood pressure in response to specific type of germs in our gut!

Here is her Ted talk, it’s worth a listen.

What Does This Mean?

There are several implications of this. First is that our body seems to sense what we eat, and reacts accordingly. Specifically, it seems to “taste” the kind of food we eat. This supports Michael Pollan’s argument that we can’t simplistically break down what we into “carbohydrates”,”protein”, and “fat.” Our body seems to sense what kind of fat we eat, taste the specific kind of fruit we eat, and act accordingly. When we eat a lot of autumn food (grains, sugar), our body seems to act as if it’s autumn, and start storing away fat for the winter, for example.

Second, losing our sense of smell may be really important for our overall health. Normal sense of smell and taste may not be just a nice-to-have.

Third, drinking diet soda ain’t gonna help you. In fact, studies have shown that drinking diet soda may have no impact on the incidence of diabetes or weight, though the results are mixed. There are sweet taste receptors in the gut, and diet drinks stimulate those receptors, triggering release of insulin. Insulin, as I’ve mentioned before, directly stimulates fat storage.

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