A study in the journal of Bone and Mineral Research published in 2010, sought to answer this very question. We already know low sodium is linked to falls and imbalance so if it also causes bone weakness it’s a pretty scary proposition. We also know about 1/3 of total body sodium is in the bones so if your blood sodium is low it’s likely leeching out from your bones to compensate.

The investigators initially looked at a rat model of Hyponatremia (low sodium). They discovered that after only 3 months the bone density was decreased by 30% compared to rats with normal sodium levels. Microscopically what they realized is the low sodium seemed to cause more bone break down and less bone building. This was quite concerning and so they next turned to human data.

The investigators looked at a large cohort of adults aged 50 plus (called NHANES 3), and did some predictive modeling. They discovered a striking 2-3 fold increased risk of osteoporosis in the low sodium group.

Another study published in 2015 in the journal of Clinical Endocrinology and Metabolism found similar results. These investigators looked at a very large cohort of US adults. They used regression models to look at the odds of both recent and chronic low sodium and osteoporosis. They found similarly a 3-4 fold increase risk of osteoporosis and low sodium. They also noted the lower the sodium and the longer the sodium was down the higher the risk for osteoporosis.
​
This data plus the known increased fall and fracture data confirms that even mild Hyponatremia should be treated and monitored closely with special care and attention to overall bone health.

To find good affordable treatment option for low sodium check us out KidneyAide.com


​Here’s links to the articles
https://pubmed.ncbi.nlm.nih.gov/19751154/
https://academic.oup.com/jcem/article/100/8/3021/2830001?login=true

​

Hyponatremia may be associated with Hypothyroidism (low thyroid levels/function), especially with severe hypothyroidism and myxedema. Myxedema is a constellation of symptoms associated with severe hypothyroidism including:

•Confusion
•Swelling
•Hypothermia (low body temperature)
•Bradycardia (slow heart rate)
•Hypotension (low blood pressure)
•Hypoglycemia (low blood sugar)

With this being said thyroid function is often checked, with a simple blood test, to be sure this is not the cause of the low sodium level.

In those with myxedema, it’s the decrease in cardiac output which leads to the release of ADH (anti diuretic hormone) via carotid sinus baroreceptors. The ADH release is the signal that tells the kidney to reclaim and hold on to water, which ultimately dilutes the sodium level in the blood. Slower kidney function (GFR) may also be contributing via the kidneys inability to excrete excess water properly.

It is interesting however, that often these hypothyroid cases mimic SIADH, with high, rather then low urine sodium, despite the low cardiac function.

In closing, we want to be sure that thyroid levels are tested as part of the workup for SIADH/Hyponatremia.

Useful links and sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470237/#__sec2title

​https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450783/

https://www.webmd.com/a-to-z-guides/myxedema-coma#2-3

​https://www.aafp.org/afp/2000/1201/p2485.html

​https://healthjade.net/myxedema-coma/

INTRODUCTION: HYPONATREMIA SIGNS AND SYPMTOMS. Hyponatremia, low blood sodium level, is a relatively common condition. Hyponatremia is the most common electrolyte disturbance to impact patients in clinical settings1. Most often, Hyponatremia is due to the inability of the body to excrete excess water. This excess water accumulates in the blood, dilutes the sodium level, and leads to low blood sodium levels. The effects of Hyponatremia and low blood sodium levels include:

• Drowsiness
• Falls
• Disturbances in bone health
• Slowness of thought
• Seizures
• Brain swelling
• And even death2

The only way for a Hyponatremia diagnosis is with a blood test. Your doctor may also check urine testing, specifically urine electrolytes and osmolarity (concentration). These tests together with a thorough history, medication review and physical examination will help tease out the cause of the water imbalance.

WHAT CAUSES THE BODY TO HOLD WATER TOO TIGHTLY?
There are many possible Hyponatremia causes. The way I like to explain it is to consider our evolution. When we were living in the stone ages and a saber tooth tiger was chasing us, or we were under a great deal of stress due to difficulty finding clean water sources, our body was programmed to hold water tightly, to avoid dehydration.

Fast forward to 2020, and we find different ‘stressors’ that may signal the body to hold water to tightly. These 'stressors' include:

• Lung diseases (COPD, cancer, infection)
• Brain diseases (cancer, strokes, scarring, infections)
• Pain-including arthritis
• And nausea (especially after surgery).

Other potential Hyponatremia etiologies include thyroid disturbances, medications especially thiazide diuretics and anti-seizure, as well as adrenal insufficiency.

The hormone that is secreted in these disease states is called Anti-Diuretic Hormone (ADH). ADH does just what its name implies; it is anti-diuresis (urinate). The urine turns dark and concentrated, and water excretion comes to a near halt.

HYPONATREMIA TREATMENT
For starters, we must be sure there aren't other reasons for the dilution effect. Examples of this include heart failure and liver disease. Both can cause fluid retention due to different mechanisms. These diseases are often treated with a low sodium diet and diuretics (fluid pills). Hyponatremia may also be caused by excessive water intake relative to solid food intake. This is termed primary polydipsia or tea and toast. These diseases are treated with simple fluid restriction and an increase in food intake.

Let's think back to the causes of Hyponatremia. Now that we have talked about the other processes, the term SIADH always gets brought up. This is a syndrome of inappropriate antidiuretic hormone release. A bit confusing, but if you follow the name, it is an improper release of the hormone that does not allow the kidney to release water. This is what occurs in those examples, as mentioned earlier, the lung disease, brain disease, pain, or nausea scenarios.

SIADH will therefore cause the kidney to hold water inside and not release it, diluting the sodium level in the blood and lead to some of those ominous symptoms.

To treat this SIADH process, we must start with a fluid restriction as a part of a Hyponatremia diet. Usually, this would be about 1 liter (32 oz) or less per day. This does include all liquids and not just water. Often that is not enough, and the patient will require further interventions. In previous days we may have used diuretics and salt tablets for Hyponatremia, however more recent studies have shown this to be somewhat ineffective when compared to fluid restriction alone and have significantly more side effects.3

More recently, Tolvaptan has come to market. Tolvaptan is an oral antagonist (blocker) of the ADH receptor in the kidney. This medication works by blocking the signal and thus allowing the body to expel all that excess water.However, this medication's downsides are high cost at over $300 a tablet and low but severe liver injury potential. There are also side effects, including overcorrection of the sodium level (which can be quite dangerous), urinating excessively at night, and extreme thirst with Tolvaptan.

Lastly, there is oral Urea for the treatment of SIADH. Urea works by osmosis. It draws water out naturally through the kidney, ridding the body of excess water without the need for salt tablets or extreme fluid restrictions. Urea is a medical food and is thus allowed to be purchased directly by the patient without a prescription. Medical foods like Urea should be taken only under the supervision of a medical practitioner. Urea has minimal if any side effects. It truly is a natural product, medical food, and not a pharmaceutical agent. Urea has a somewhat intense, slightly salty taste and is thus best made palatable by flavorings.

Our company, KidneyAide.com, maker of UreaAide, is an example of this with a natural refreshing mint flavor, dosed in individual packs, and easily purchased online. We will soon be expanding into other flavors and a low-cost plain version that could be mixed with other flavorings at home. This will offer patients lots of options in terms of flavors and lower the cost for everyone.

In closing, Hyponatremia or low sodium is a common disorder that may cause multiple vague symptoms which only a blood test can detect. A thorough investigation is necessary to tease out the reason for the disturbance. There are several ways to treat Hyponatremia. With the example of SIADH fluid restriction, urea products such as UreaAide, Tolvaptan, or salt plus water pills may all be options to help rid the body of excess water and get the sodium level back into the normal range. Thus alleviating the symptoms of low sodium and getting back to feeling great again.

Citations
1. Upadhyay A, Jaber BL, Madias NE. Incidence and prevalence of hyponatremia. Am J Med. 2006 Jul;119(7 Suppl 1):S30-5. doi: 10.1016/j.amjmed.2006.05.005. PMID: 16843082.
2. Goce Spasovski, Raymond Vanholder, Bruno Allolio, Djillali Annane, Steve Ball, Daniel Bichet, Guy Decaux, Wiebke Fenske, Ewout J. Hoorn, Carole Ichai, Michael Joannidis, Alain Soupart, Robert Zietse, Maria Haller, Sabine van der Veer, Wim Van Biesen, Evi Nagler, on behalf of the Hyponatraemia Guideline Development Group, Clinical practice guideline on diagnosis and treatment of hyponatraemia, Nephrology Dialysis Transplantation, Volume 29, Issue suppl_2, 1 April 2014, Pages i1–i39
3. Efficacy of Furosemide, Oral Sodium Chloride, and Fluid Restriction for Treatment of Syndrome of Inappropriate Antidiuresis (SIAD): An Open-label Randomized Controlled Study (The EFFUSE-FLUID Trial) Krisanapan P., Vongsanim S., Pin-on P., Ruengorn C., Noppakun K. (2020) American Journal of Kidney Diseases, 76 (2) , pp. 203-212.

1. Urea’s molecular formula is CO-(NH2)2. Pubchem.

2. Urea is also known as Carbamide, 57-13-6, Carbonyldiamide, IsoUrea. Pubchem

​3. Urea is found naturally in our skin and is one of our body’s natural moisturizers. Many skin care products contain Urea at various percentages, Eucerin 10% Urea is an example of one.
​
4. Urea has a molecular weight of 60.056 g/mol very similar to Sodium Chloride 58.44 g/mol (that’s why 1 packet of 15 g UreaAide is equal to ~7 salt tablets).

​5. Urea is formed naturally in the liver. The liver, via the urea cycle, takes 2 toxic Ammonia molecules from protein breakdown plus Carbon Dioxide to form 1 Urea molecule. Urea May then be excreted safely through the urine.

6. An IV formulation of Urea Ureaphil (40 grams/vial) was available, and first used in the 1960’s for increased intracerebral pressure. Ureaphil was later discontinued in 2006, as other products like mannitol came on to market.

​7. Urea 13-C is a radiolabelled urea molecule used in the diagnosis of stomach ulcers by the bacterium Helicobacter Pylori. H. Pylori contains the enzyme Urease which will break down Urea to Ammonia and radioactive C02 where the CO2 can be detected in the breath. C-13 Urea breath test

​8. Urea is considered extremely safe and there are no reports, to our knowledge, of Osmotic Demyelination with the us of Urea for Hyponatremia.

9. Urea has been used for SIADH since at least 1980 where G Decaux et al. showed it’s effectiveness and published the data in the American Journal of Medicine.

10. Over 90% of oral Urea is absorbed in the upper GI tract. Urea has a half life of only about 2 hours, and an oral dose of Urea is completely excreted by the kidneys by 12 hours. Blood Purif 2020;49:212–218
​

Pseudohyponatremia, as the name implies, is not what we consider true hyponatremia. In fact, it is a laboratory error (pseudo-greek derivation meaning false; feigned). When serum sodium is measured with the standard indirect ion-selective electrode (ISE) method it is measured in an aqueous solution, diluted, and there is always an assumption that plasma is precisely 93% water. When the samples are analyzed and something in the sample is "displacing" the plasma water, then the actual amount of sodium detected will be lower. What can displace the plasma water? Lipids, as in a very high triglyceride levels for starters. These elevated triglyceride levels, typically >1500 mg/dl, are often seen in conjunction with pancreatitis. Elevated proteins may also lead to Pseudohyponatremia; typically seen with diseases like Multiple Myeloma with total proteins in excess of 10 g/dL. Lastly, in severe biliary obstruction we may see very high levels of cholesterol and lipoproteins (lipoprotein x) usually with cholesterol levels over 1000 mg/dL.
This error can be avoided if a whole blood sample is drawn and analyzed with direct ion-selective electrode like the arterial blood gas method. Because this is not true hyponatremia, the treatment is directed at the underlying process and not on the low sodium.

Urea has been used for many years and in many countries for the treatment of SIADH/Hyponatremia. Urea is considered a GRAS (generally recognized as safe) product by the FDA1. In fact, an interesting study took place in Belgium in 2012. They looked at 12 patients with chronic SIADH, with an average sodium of 125 meq/L (low). The first year, they were given the new, very expensive, pharmaceutical drug class Vaptans daily. The average Sodium came up to a normal level of 135 meq/L. 1 patient out of the 12 dropped out due to severe thirst. Next, the patients had an 8 day “holiday” without treatment, and as expected the Sodium went back down (pictured above). Over the next 12 months, the SIADH patients were given oral Urea therapy. The patients now on Urea have a similar normal sodium level of 135 meq/L. However, this time there were no dropouts nor any significant adverse events. The authors, therefore concluded that oral Urea was safe, well tolerated and as effective as the Vaptans at a much lower cost.2 This study impacted the current European best practice guidelines which advocate for Urea over Vaptans for SIADH/Hyponatremia.3
Another study, this time out of Italy, looked back from years 2013-2018 on 36 patients with cancer associated SIADH/Hyponatremia. They were treated with Urea, and had an average sodium 1 point lower at 124 meq/L (low). They noted after only 24 hours of treatment, the sodium improved on average by 5 meq/L. Secondarily, the Italian physician scientists discovered over 90% of patients on 60 days of treatment with Urea, achieved a normal sodium level. The authors, therefore concluded oral Urea was safe, effective beginning first day of treatment, and very well tolerated.4

Urea has been used for many years in multiple countries for SIADH/Hyponatremia. Urea has always shown to be safe and effective even when taken for a year or more. Our version of this miraculous medical food is UreaAide which can be found by clicking here KidneyAide.

​
Links to the FDA, CJASN and Endocrinology studies + European guidelines for Hyponatremia.
1.https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1923

2.https://cjasn.asnjournals.org/content/7/5/742

3. http://www.european-renal-best-practice.org/sites/default/files/u33/short%20version%20hyponatraemia%20English%20FINAL.pdf

4.https://onlinelibrary.wiley.com/doi/full/10.1111/cen.13966

Hyponatremia, or low sodium, is quite common affecting estimates of 1.7-2.1% of the US population1. There are many causes of Hyponatremia (low serum sodium). For completeness, there are less common causes of Hyponatremia, such as the type associated with hyperglycemia (very high blood sugar) or seen with extremely high lipids or protein levels termed ‘’pseudohyponatremia’. These types are looked at and treated differently then the more common hypotonic Hyponatremia that most patients have.
It’s very important that we recognize something first, nearly all Hyponatremia is caused by the dilution effect of excess water in the blood. This excess water dilutes the sodium level to below 135 meq/L. It’s in this context that we discuss the major causes of Hyponatremia.

Lets start with medications. There are many medications that lead to Hyponatremia, thiazides diuretics being the most common culprits.
Other drugs commonly implicated are antidepressants and anticonvulsants. Street drugs such as ecstasy, bath salts, and amphetamines are also possible causes.

One question that is often brought up is, ‘doctor can I drink too much water?’
Answer, a resounding yes with some caveats.
​Its relative to the solute or food you consume. Your kidney can usually do a great job of ridding your body of excess water. Even the great kidneys, however, have their limits. The lowest dilution the kidneys can ever get down to is 50. 50 what you ask? 50 milliosmoles/Liter (mOsm/L). This implies that your kidney needs at least 50 mOsm/L of ‘stuff’ to get rid of that Liter of water you drank. The ‘stuff’ is food like protein (Urea), salt and potassium. The average person eats about 900 mOsm per day. So consider that scenario of 50 osm/L. The implication here is 900 mOsm/50 mOsm/L is 18 liters a day of water one could excrete. That’s over 4 gallons! So if your eating normally you’d have to drink an awful lot to dilute your sodium. This is actually termed psychogenic polydypsia when it happens. On the other hand, if your not eating all that well, say only 250 mOsm/day, then it’s 250/50= 5 liters. Often however, as we age the kidney may only get down to 100 osm dilution. Now 250/100 is only 2.5 liters of water before you start diluting. This type of Hyponatremia is called ‘’tea and toast’ or ‘beer potomania’ (when it’s beer as the main liquid). So yes you can drink too much water even if your kidney is doing it’s very best. Now what if your kidney is getting the wrong signal?

Syndrome of inappropriate ADH secretion or SIADH is just that, inappropriate signal. ADH is anti-diuretic hormone, meaning when it’s around you anti diurese (make less urine). When ADH is on board the kidney holds water very tight and your urine turns darker and more concentrated. Over several days of drinking water and other liquids, your serum sodium will become diluted.
​
So what causes the ADH to be excreted?
Common triggers for ADH are nausea and pain; that’s why we often see SIADH after surgeries. Other triggers are Lung disease including cancer (especially small cell) and brain diseases such as stroke, bleed, or infection. These SIADH scenarios respond best to UreaAide because the Urea induces a nice osmotic diuresis. The osmotic diuresis will counteract the dilution effect and raise the serum sodium level.

Another cause of low sodium levels are true volume depletion from vomiting and diarrhea. Here your body will also excrete ADH but this time the signal is appropriate. This is termed effective arterial volume depletion. This type of hypovolemic Hyponatremia usually corrects with iv fluids.

Other reasons your sodium could be low include: heart failure, cirrhosis of the liver, hypothyroidism, and adrenal Insufficiency. These tend to be obvious in terms of heart or liver disease, however thyroid or adrenal must be considered and tested for.

As you see their are a lot of scenarios in which the sodium may drop and your doctor will work with you to figure out why. The key is making the correct diagnosis and then recommending the best treatment.



1. Am J Med. 2013 Dec; 126(12): 1127–37.e1.
doi: 10.1016/j.amjmed.2013.07.021
PMID:24262726

There is no such thing as asymptomatic Hyponatremia. We were all taught this in medical school and residency, but what are the problems of leaving your serum sodium a little on the low side?
Based on many different studies both observational and randomized ie: SALT-1 and SALT-2, below are 5 of the more common and ominous risks associated with Hyponatremia especially, a Sodium <130 meq/L

1. Increased risk of osteoporosis-bone disease

2. Increased risk of falls and hospitalizations

3. Increased risk of kidney stones

​4. Increased risk of confusion/lethargy/weakness

5. Increased risk of mortality-dying

The good news is there is a simple, safe, and effective way to get your sodium back to normal with UreaAide!

Check it out here click the button below

UreaAide works by osmosis. It really is that simple. When you have excess water (SIADH/Hyponatremia) it is that excess water that is diluting your sodium and causing the number to be low. UreaAide works by increasing the osmolarity (concentration) in the urine which will ultimately draw water to flow in the urine out of the body. As this water leaves the body the dilution effect decreases and the sodium rises. It really is that easy.