Boosting Insulin Sensitivity with Nitric Oxide

We have four main homeostatic regulators of the body; pH, temperature, O2/CO2, and blood sugar. Insulin plays a vital role in maintaining our blood sugar. Because of this, staying insulin sensitive is vital to human health. Over the course of a lifetime, as your cells stop responding to insulin (from a high processed/high sugar diet) we become pre-diabetic, then progress to diabetes. All cells of the body have insulin receptors, so when they stop responding to insulin, a whole host of problems can arise. Luckily, there are lots of natural ways to improve insulin sensitivity. As it turns out, a molecule called nitric oxide (NO) is one of many ways to improve insulin sensitivity.

Nitric oxide is a gaseous signaling molecule that is produced by the endothelial cells lining your blood vessels. It has a number of important physiological functions, most notably its ability to dilate blood vessels, which improves blood flow. This process is called vasodilation, and it allows for better circulation and the delivery of oxygen and nutrients to tissues throughout the body.

Nitric oxide also has an impact on cellular function, including its effects on metabolism and insulin sensitivity. It plays a crucial role in helping your body utilize insulin more efficiently, which is why it's increasingly being recognized as an important factor in managing and preventing metabolic conditions like insulin resistance.

Nitric oxide enhances insulin action by improving blood flow and promoting the transport of glucose into cells. Here’s how it works:

1. Improved Blood Flow and Glucose Delivery: As nitric oxide causes vasodilation, it increases the blood flow to muscles and tissues. This means that glucose, which is transported through the bloodstream, can reach cells more efficiently. As a result, the cells are better able to respond to insulin, allowing for more effective glucose uptake and better blood sugar regulation.
   

2. Reduced Inflammation: Chronic inflammation is a key contributor to insulin resistance. Nitric oxide has anti-inflammatory properties, which can help lower levels of inflammation in the body. By reducing inflammation, nitric oxide can help prevent the onset of insulin resistance and improve overall metabolic health.
   

3. Muscle Function and Insulin Sensitivity: Nitric oxide has also been shown to improve muscle function and energy production. Since muscles are key players in glucose uptake and storage, improved muscle function can enhance insulin sensitivity. When muscles are more responsive to insulin, they can better absorb glucose and store it as glycogen, thus helping to maintain balanced blood sugar levels.
   

4. Endothelial Health: Nitric oxide is crucial for maintaining the health of the endothelium (the lining of your blood vessels). A healthy endothelium ensures proper blood flow and circulation, which is vital for nutrient and oxygen delivery. Proper endothelial function is directly tied to insulin sensitivity, as poor circulation can impair glucose and insulin transport.
   

Natural Ways to Boost Nitric Oxide

While your body naturally produces nitric oxide, lifestyle factors like diet, exercise, and sleep can influence its production. Here are some natural ways to boost nitric oxide levels in your body:

1. Nitrate-Rich Foods

Nitrates, which are found in certain vegetables, are converted into nitric oxide in the body. Foods that are particularly high in nitrates include:

• Beets: Beets are packed with nitrates, which are quickly converted to nitric oxide. Consuming beet juice or roasted beets can have a profound effect on nitric oxide levels.
  

• Leafy Greens: Vegetables like spinach, arugula, kale, and swiss chard are also rich in nitrates.
  

• Radishes: Another nitrate-rich vegetable that can contribute to increased nitric oxide levels.
  

2. Foods High in Antioxidants

Antioxidants play an important role in protecting nitric oxide from being broken down by free radicals. Certain foods can enhance nitric oxide production and protect it from oxidative stress. Some of the best foods for boosting nitric oxide include:

• Berries (blueberries, strawberries, raspberries)
  

• Citrus fruits (oranges, grapefruits, lemons)
  

• Dark chocolate (in moderation, with at least 70% cocoa)
  

• Pomegranate: This fruit is rich in antioxidants and has been shown to improve nitric oxide levels.
  

3. Exercise Regularly

Exercise, particularly aerobic and resistance training, can naturally boost nitric oxide production. Physical activity stimulates the endothelial cells to release more nitric oxide, which leads to better circulation and improved insulin sensitivity.

• High-intensity interval training (HIIT) has been shown to be particularly effective at boosting nitric oxide production and improving insulin sensitivity.
  

• Even moderate exercise, such as walking or swimming, can have a positive impact on nitric oxide levels.
  

4. Get Enough Sleep

Adequate sleep is essential for maintaining healthy nitric oxide levels. Sleep deprivation can impair the body’s ability to produce nitric oxide, which can negatively impact insulin sensitivity and overall metabolic health. Aim for 7-9 hours of quality sleep each night to help regulate nitric oxide production.

5. L-Arginine and L-Citrulline 

L-Arginine and L-Citrulline are amino acids that act as precursors to nitric oxide. By consuming foods rich in these amino acids or taking supplements, you can boost nitric oxide levels. Some good sources of L-Arginine and L-Citrulline include:

• Watermelon: This fruit is a rich source of L-Citrulline, which can enhance nitric oxide production.
  

• Nuts and seeds: Almonds, walnuts, and sunflower seeds are good sources of L-Arginine.
  

• Lean meats and fish: Chicken, turkey, and salmon also contain L-Arginine.
  

6. Stay Hydrated

Dehydration can impair nitric oxide production, so it’s important to stay hydrated throughout the day. Drink plenty of water to support the body's natural functions, including the production of nitric oxide.

What Really Causes Gout?

Gout is a type of inflammatory arthritis that typically attacks the big toe and ankle. Gout primarily occurs when there is an accumulation of uric acid crystals in the joints, leading to inflammation and intense pain. Uric acid is a normal waste product that forms when the body breaks down purines, substances found in certain foods and also produced by the body. Normally, uric acid dissolves in the blood and passes through the kidneys into the urine. However, if too much uric acid is produced or if the kidneys do not eliminate enough of it, uric acid can build up, leading to gout.

It tends to attack the feet and toes because of temperature and gravity. The peripheral parts of the body are cooler than the core which allows uric acid to crystalize. It’s classically called a “disease of kings” because of the association of rich diets and alcohol. How accurate is this? Like most conditions of the body, there is more nuance to this. Research has confirmed that purine rich foods can contribute to the development of gout, but many of these foods are animal products such as red meat, turkey, organ meat etcetera, that are nutrient dense. Do we need to give these foods? This is a classic case of correlation does not equal causation. 

Some studies have found that ingesting high levels of purines is not enough to provoke a gout attack (Zhang, 2021). Other studies found that consumption of purines and proteins increases the excretion of uric acid and is associated with increased inflammatory markers such as CRP and IL-6 (Urano et al., 2002). So what is going on here?

This is a bit of an innocent bystander effect and is similar to the sugar and salt debate as it pertains to high blood pressure. Salt does increase blood volume but normally the kidneys are able to regulate salt levels. However, in the context of a high sugar diet and insulin resistance, the kidneys lose this regulating ability and retain too much salt. So salt takes the blame, when insulin resistance is the real problem. This is more or less the same situation, and it appears, possibly the same culprit; insulin resistance. Hyperinsulinemia causes a decrease in urinary excretion of uric acid (Galvan, 1995). So it appears that high levels of purines result in elevated uric acid which the kidneys will normally excrete. In an insulin resistant state, we do not excrete adequate levels of uric acid leading to a “back up” effect.

There are some other players that may be contributors to gout flare ups. Fructose (as in high fructose corn syrup) appears to have a role. It can increase serum uric acid levels by enhancing the production of purines and reducing uric acid excretion. Iron is another marker that tends to be elevated which is no surprise given the correlation between increased iron and diabetes.

So what can we do about this? Lowering sugar levels and alcohol intake will certainly help. Vitamin C increases the excretion of uric acid and this is part of why cherry juice is recommended for gout. Blood donation reduces iron levels, so it would stand to reason it would reduce gout. In 2003, a study by Facchini found that phlebotomy to a near iron deficient state affected gout ranging from a complete remission to a marked reduction of incidence and severity of gouty attacks.

So if you do get a gout attack, it’s probably a good idea to get a blood panel. Besides uric acid, I’d be looking out for blood sugar markers, as this may be a sign of insulin resistance. I’d look at inflammatory markers, and iron/ferritin levels. 

Want more help? Let’s get on a free consult call:

References:

Facchini FS. Near-iron deficiency-induced remission of gouty arthritis. Rheumatology (Oxford). 2003 Dec;42(12):1550-5. doi: 10.1093/rheumatology/keg402. Epub 2003 Jun 27. PMID: 12832712.

Quiñones Galvan A, Natali A, Baldi S, Frascerra S, Sanna G, Ciociaro D, Ferrannini E. Effect of insulin on uric acid excretion in humans. Am J Physiol. 1995 Jan;268(1 Pt 1):E1-5. doi: 10.1152/ajpendo.1995.268.1.E1. PMID: 7840165.

Wako Urano, Hisashi Yamanaka, Hiroshi Tsutani, Hiroshi Nakajima, Yuko Matsuda, Atsuo Taniguchi, Masako Hara, Naoyuki Kamatani

The Journal of Rheumatology Sep 2002, 29 (9) 1950-1953;

Zhang WZ. Why Does Hyperuricemia Not Necessarily Induce Gout? Biomolecules. 2021 Feb 14;11(2):280. doi: 10.3390/biom11020280. PMID: 33672821; PMCID: PMC7918342.

High Blood Pressure? Drop the Sugar.

For years, we’ve been told to avoid salt as it increases blood pressure. There is more to the story than that. After all, there is what is known as “salt sensitive hypertensives”. So why do some people seem to be sensitive to salt, and others are not? Whenever this pattern arises, there is some more digging to be done. Perhaps the link is sugar.

But first, let’s discuss how salt can raise blood pressure. Salt is necessary for human life and it’s part of muscle contraction. Our bodies rely on a balance of water and salt. This balance is detected in our kidneys, which signals to our endocrine system where the balance stands. Too much salt, the pituitary secretes vasopressin to tell the kidneys to hold on to water. Not enough salt, the adrenal glands secrete aldosterone to tell the kidneys to hold on to salt. 

Water chases salt, so where there is more salt, there is more water, and total blood volume increases. This means blood pressure will increase as well. Increased insulin levels raise aldosterone (Kubzansky & Adler, 2009). A diet that is chronically high in carbohydrates will lead to insulin resistance, and therefore more aldosterone when carbs are eaten. So this may explain why some are sensitive to salt, and some are not. Perhaps those that are salt sensitive, are insulin resistant. Quite simply: a diet high in carbs>insulin resistance>increased aldosterone>increased salt and water retention>elevated blood pressure. 

Another way that sugars may increase blood pressure is through its effect on the blood vessels. Insulin has two important effects on the vasculature. Normally, insulin suppresses cytokines, adhesion molecules, and reactive oxygen species (the damaging stuff for vessels). It also stimulates nitric oxide release, a known vasodilator (widens the vessel). In an insulin resistant state, this hormone no longer exhibits its effects (Fonseca, 2007). So now you have a tube that is thickened from the inside, and narrowed because of the lack of nitric oxide; a double whammy.

That’s 3 ways that sugars can increase blood pressure. And that’s just what we know of. Time and time again, we learn that the farther we stray from how our ancestors ate, the worse our health becomes. 

References:

Fonseca VA. The effects of insulin on the endothelium. Endocrinol Metab Clin North Am. 2007 Dec;36 Suppl 2:20-6. doi: 10.1016/s0889-8529(07)80009-0. PMID: 18407031.

Kubzansky LD, Adler GK. Aldosterone: a forgotten mediator of the relationship between psychological stress and heart disease. Neurosci Biobehav Rev. 2010;34(1):80-86. doi:10.1016/j.neubiorev.2009.07.005

Type 3 Diabetes

Type 3 diabetes is a new (and not quite accepted yet) term to describe the effects that diabetes can have on the brain. It describes the progression of diabetes to Alzheimer’s disease. The correlation between diabetes and Alzheimer’s is well documented, and this blog will aim to describe the proposed mechanism.

Just a quick reminder; diabetes is directly affected by insulin. There is either not enough insulin (type 1), or too much production due to insulin resistance (type 2). Type 2 diabetes is the one that is implicated in Alzheimer’s disease. 

Alzheimer’s is complicated, and the current understanding of the disease process postulates that progression is due to a build up of a protein called amyloid beta peptide. These form plaques that affect brain function. Your brain cells have receptors of insulin, so when it is released from the pancreas, it has a direct effect on the brain. When the brain becomes insulin resistant, more insulin has to be released to have the intended response. The plaques in patients with Alzheimer’s are formed in the space between nerves of the brain, not inside the nerves. An overabundance of insulin causes the nerves to release the amyloid beta protein into the space between the nerves (Gasparini et al., 2001). 

Alzheimer’s accounts for about 80% of all dementia. Vascular dementia is another form where the blood vessels aren’t functioning normally. There is a cause and effect relationship between hyperinsulinemia and hypertension. Insulin increases blood pressure by increasing sodium absorption in the kidneys, activating the fight or flight nervous system, and causing the blood vessels to thicken. Conversely, high blood pressure causes decreased delivery of insulin and glucose to the muscle cells, resulting in impaired glucose uptake (Salvetti et al., 1993). 

These are just a few of the mechanisms of how insulin resistance may be causing dementia. The more you read on insulin resistance, the more you learn just how horrible it is. For example, too much insulin will make you gain weight. Fat cells are like endocrine organs, meaning they can secrete signaling molecules. One of the molecules they secrete is cytokines, which cause inflammation. Inflammation causes further insulin resistance, which causes more inflammation, and the cycle repeats. This chronic systemic inflammation eventually reaches the brain. 

Another problem is that many people are insulin resistant and have not been diagnosed. If you are overweight and have high blood pressure, you are very likely to have insulin resistance. A few other signs of insulin resistance are dark patches of skin around the armpits and neck, and also skin tags which are little growths of skin. By the way, you don’t have to be overweight to be insulin resistant. You can be T.O.F.I., which stands for “thin on the outside, fat on the inside”. Fat can form around your organs. 

If you have some of these symptoms, you may want to speak to your physician about adopting a low carb, high fat diet. Also, you can order a self test kit to check your A1C. Find the test here, and use the code DPT20 for 20% off. 

References: 

Gasparini, L., Gouras, G. K., Wang, R., Gross, R. S., Beal, M. F., Greengard, P., & Xu, H. (2001). Stimulation of β-Amyloid Precursor Protein Trafficking by Insulin Reduces Intraneuronal β-Amyloid and Requires Mitogen-Activated Protein Kinase Signaling. The Journal of Neuroscience, 21(8), 2561–2570. https://doi.org/10.1523/jneurosci.21-08-02561.2001 

Salvetti, A., Brogi, G., Di Legge, V., & Bernini, G. P. (1993). The Inter-Relationship between Insulin Resistance and Hypertension. Drugs, 46(Supplement 2), 149–159. https://doi.org/10.2165/00003495-199300462-00024