Rocky Mountain Family Chiropractic

Using nitric oxide to modulate autoimmune activity

IL-17 does its dirty work of destroying tissue by activating a compound called inducible nitric oxide.

Nitric oxide is a gas in the body that acts as a signaling compound, triggering things to happen. It plays a role in many normal physiological processes, but also in disease. There are three forms of nitric oxide, two of which are beneficial, and one of which is destructive.

Exercise enthusiasts take an amino acid supplement called arginine to boost nitric oxide, as the beneficial forms of nitric oxide promote blood flow and the dilation of blood vessels. Bodybuilders like this because increasing blood flow to their muscles enables them to lift heavier weights, work out longer, and recover faster, thus building more muscle. Good nitric oxide activity has also been shown to lower the risk of cardiovascular disease. [2]

The good and the bad of nitric oxide

Unfortunately, arginine may also increase a very pro-inflammatory and damaging form of nitric oxide called inducible nitric oxide.

Researchers have found that when an autoimmune reaction creates a surge in TH-17 activity, it stimulates an enzyme called inducible nitric oxide synthase (iNOS) to produce more inducible nitric oxide. When TH-17 goes up, iNOS goes up, and inducible nitric oxide sets about destroying body tissue, such as the thyroid gland, erroneously targeted by the dysregulated immune system.[3] [4] [5]

In other words, TH-17 gives the orders to attack, but inducible nitric oxide is the perpetrator that carries out the dirty work. Unfortunately, people who take arginine may be subjecting themselves to unnecessary increases in iNOS activity, and hence more inflammation.

Like TH-17, iNOS isn’t all bad. It’s pro-inflammatory role comes in handy to combat viruses, bacteria, and other pathogens.[6] But the health imbalances that lead to autoimmune disease are the same ones that over stimulate the production of iNOS that destroy body tissue.[7]

We can test TH-17 levels just as we can test for TH-1 and TH-2. This is helpful because if a lab panel shows TH-17 cytokines to be elevated, this tells us tissue is actively being destroyed and it’s vital to quench that process.

The good news and the bad news about nitric oxide

Body builders who take arginine think nitric oxide is good. A practitioner seeking to tame the destruction of an autoimmune process may look upon nitric oxide as bad. Which is it? It depends on the form of nitric oxide the body is producing.

So far I have talked about inducible nitric oxide, which a TH-1 or TH-2 triggered autoimmune attack activates via TH-17 to destroy tissue. For people experiencing autoimmune flare-ups, this system is in overdrive.

However, we can combat this destruction by activating the two beneficial forms (technically called isomers) of nitric oxide called endothelial nitric oxide and neuronal nitric oxide.

Endothelial nitric oxide

Endothelial nitric oxide is found in the lining of blood vessels. It aids in tissue recovery and regeneration, enhances blood flow, dissolves plaques, and dilates blood vessels. One thing that dramatically activates endothelial nitric oxide is exercise. When you exercise, the increase in blood flow turns on the endothelial nitric oxide system, which helps dissolve plaque in the arteries.

Unfortunately, autoimmune disease often compromises this system, thus hindering the delivery of blood to body tissue.[8] This not only makes body tissue, such as the thyroid gland, more vulnerable to inflammation and destruction, but it also makes it more difficult for these tissues to recover and heal.

A weak endothelial nitric oxide system helps explain cold hands and feet, the loss of hair, weak nails prone to fungal infections, and other symptoms frequently found in conjunction with autoimmune diseases.

Poor blood flow robs the brain of blood, and hence oxygen and nutrients, and brain function deteriorates.

Poor blood flow to the digestive tract is one cause of leaky gut and poor gut function. Coupled with inflammation and poor glutathione activity, the person with a chronically activated autoimmune disease can never seem to repair her gut. This is why a strict autoimmune diet to protect the gut is necessary in these cases.

Overall, the research shows endothelial nitric oxide plays a big role in preventing and taming autoimmune disease, due to its inhibition of over activity of both the TH-1 and TH-2 systems.

Neuronal nitric oxide

Neuronal nitric oxide acts on the brain and nervous system, enhancing the ability of the brain and nervous system to adapt to change, communicate between neurons, and recover. Because good brain health is vital to absolutely every organ and system in the body, we want neuronal nitric oxide levels to be sufficient and active.

How to boost the good nitric oxide and dampen the bad

So we know endothelial nitric oxide helps tame the autoimmune response and aids in tissue recovery. We know we have a “bad” nitric oxide, inducible nitric oxide, which is over active during TH-17-stimulated autoimmune attacks. We also know that taking arginine is not desirable, because although it might boost endothelial and neuronal nitric oxide, it may also boost the destructive inducible nitric oxide. These are the facts I considered as a practitioner when I began exploring these mechanisms and how to further help my autoimmune patients.

The clinical goal is to modulate the TH-1, TH-2, TH-3, and TH-17 systems (by modulate, I mean influence them to behave appropriately), increase endothelial nitric oxide, and dampen the inducible nitric oxide response.

Eventually, after my ongoing review of the research and clinical experience, it became apparent glutathione pathway integrity and nitric oxide modulation (boosting the good and dampening the harmful) offered profound responses.

Nutritional compounds for nitric oxide modulation

Through reading published studies, I found a variety of nutritional compounds that have been shown to boost endothelial nitric oxide without also boosting the pro-inflammatory inducible nitric oxide. I use these nutrients together as I find they have the best effects when working synergistically:

• Adenosine
• Huperzine A
• Vinpocetine
• Alpha Glycerylphosphorylcholine (Alpha GPC)
• Xanthinol niacinate
• L-Acetylcarnitine

In my practice the use of these compounds together in an emulsified liquid formula has had profound effects in managing some of my most severe autoimmune cases, and, together with glutathione recycling, has been an exciting discovery for me as a practitioner.

For the best results take these compounds before exercise, even if it’s a walk around the block. Exercise will get the blood flowing and enhance the effects of the endothelial and neuronal nitric oxide activation.

Glutathione recycling and nitric oxide modulation—a beautiful partnership

A nitric oxide modulating and glutathione recycling approach is available through a qualified health care practitioner trained in these approaches.

The nice thing about supporting glutathione recycling and nitric oxide is that it doesn’t matter whether you are TH-1 or TH-2 dominant.

I find these approaches have been successful with my very fragile patients who react to so many foods and supplements and can’t handle the TH-1 or TH-2 stimulating compounds.

An article in the Seattle Times argues that Bill Gates’ support of genetically modified (GM) crops as a solution for world hunger is based on unsound science.  A team of 900 scientists funded by the World Bank and United Nations over the course of three years determined that the use of GM crops is not a meaningful solution to the complex situation of world hunger.

The scientists suggested that “agro-ecological” methods would provide the most viable means to ensure global food security, including the use of traditional seed varieties and local farming practices already adapted to the local ecology.

According to the Seattle Times:

“Agro-ecology has consistently proven capable of sustainably increasing productivity. Conversely, the present GM crops generally have not increased yields over the long run, despite their increased costs and dependence on agricultural chemicals”.

A new study, which examined data from 14 years’ worth of mammography screening, found that the increased incidence of breast cancer observed in that period was due to over-diagnosis.  In the absence of screenings, many of the tumors found would never have given rise to clinical illness.

The researchers noted that the effect of hormone replacement therapy could not have been responsible for the increase in breast cancer diagnoses, as the increase occurred during a period when the use of such hormones fell by 70 percent.

According to Green Med Info:

“This latest study confirms … that breast screening may have caused net harm for up to 10 years after their widespread introduction.”

By Dr. Mercola

The United States imports one-fourth of its raw sugar from Central America, a region known as much for its sandy beaches and lush rainforests as its many acres of sugar plantations.

In Central American countries like Nicaragua, finding employment is a challenge, and many residents begin working in the sugar fields when they are still children, as young as 10 years old.

It’s labor-intensive work, requiring long hours of manual labor under hot sun and high temperatures, often with few or no breaks in between.

Now, chronic kidney disease is claiming the lives of many of these young workers — to the extent that some are labeling the condition “Sugar Cane Kidney Disease” –  and researchers are scrambling to uncover the cause as the death toll steadily rises.

“The Island of the Widows”

In the United States, chronic kidney disease is typically caused by diabetes and high blood pressure, conditions that are generally not impacting the young victims in Central America.

Still, the rate of chronic kidney disease in Nicaragua is 10 times higher than in the U.S.

Furthermore, while the condition is considered treatable if detected early, in rural Central America access to medical care such as dialysis or kidney transplants is limited, and so the kidney disease advances quickly and is almost always fatal.

Daniel Brooks, a professor of epidemiology at Boston University School of Public Health, who has been investigating the mystery, told Fox News Latino:ⁱ

“Once someone gets it, it’s basically a death sentence.”

According to an analysis of health data by the International Consortium of Investigative Journalists, more than 2,800 men have died from kidney failure in Central America each year from 2005-2009. As iWatch News reported:ⁱⁱ

“In El Salvador and Nicaragua alone over the last two decades, the number of men dying from kidney disease has risen fivefold. Now more men are dying from the ailment than from HIV/AIDS, diabetes and leukemia combined.

… The surge of kidney disease is overwhelming hospitals, depleting health budgets, and leaving a trail of widows and children in rural communities. In El Salvador, CKD is the second leading cause of death for men. In the province of Guanacaste, Costa Rica, the regional hospital had to start a home dialysis program because it was overwhelmed with so many CKD victims that it began running out of beds to treat patients with other ailments. So many men have died in some parts of rural Nicaragua that … [one] community, called The Island, now is known as the Island of the Widows — La Isla de las Viudas.”

Why are so Many Young Men Dying from Chronic Kidney Disease in Central America? This is the burning question and also the heart of the mystery, because no one knows for sure. There are several plausible theories, though. In a report by Brooks and colleagues, which reviewed 22 epidemiological studies looking into hypotheses about potential causes of chronic kidney disease in Nicaragua, it’s stated:ⁱⁱⁱ

“Taken together, these studies reported fairly consistent positive associations for

(1)   agricultural work

(2)   pesticide exposure

(3)   dehydration

(4)   hypertension

(5)   lija consumption (lija is a type of rum)

(6)   family history of CKD.”

To date, no one cause has emerged as a concrete explanation, but the two theories receiving the most attention are exposure to agricultural chemicals and repeated bouts of dehydration. The sugar plantation workers are exposed to toxic pesticides on a daily basis, and it’s known that even the so-called inert ingredients in certain pesticides may cause kidney failure.^iv Dehydration, also linked to kidney disease, is also a major concern, especially amidst reports that the workers may be subjected to poor working conditions. As ABC News reported:

“Nicaragua’s highest rates of chronic kidney disease show up around the Ingenio San Antonio, a plant owned by the Pellas Group conglomerate, whose sugar mill processes nearly half the nation’s sugar.

… According to one of Brooks’ studies, about eight years ago the factory started providing electrolyte solution and protein cookies to workers who previously brought their own water to work. But the study also found that some workers were cutting sugar cane for as long as 9 1/2 hours a day with virtually no break and little shade in average temperatures of 30 C (87 F).

In 2006, the plantation, owned by one of the country’s richest families, received $36.5 million in loans from the International Finance Corp., the private-sector arm of the World Bank Group, to buy more land, expand its processing plant and produce more sugar for consumers and ethanol production.”

Why Fructose Combined with Dehydration May be the Deadly Hidden Culprit

Fructose metabolism is quite different from glucose (dextrose) metabolism in that it places the entire burden on your liver, and this accounts for many of its devastating health effects. However, it appears that the Central American workers may be engaging in the “perfect storm” of activities for fructose to cause devastating damage to their kidneys.

As explained by Dr. Richard Johnson, chief of the division of kidney disease and hypertension at the University of Colorado, in his upcoming book The Fat Switch, this mystery illness likely starts with dehydration and is then made worse by the fact that many workers drink sugar-sweetened pineapple or mango juice or soft drinks (all high in fructose) to rehydrate.

Let me explain …

When you consume fructose, some of it is filtered in your kidneys and taken up into your tubules. Indeed, studies have linked soft drinks and high-fructose diets with kidney disease and accelerated kidney damage. But there is another, even more sinister, effect that appears to be harming young men working in the sugar cane fields.

Your body is capable of converting glucose into fructose via a mechanism known as the polyol pathway. This is especially common among people with diabetes or those who are severely insulin resistant, but the polyol pathway is also activated by dehydration.

So as the Central American workers become dehydrated, the polyol pathway is activated in their kidney tubules, converting glucose to fructose. Meanwhile, the workers take in even more fructose in the form of fruit juice and soda during their workday. This leads to a massive increase in fructose that is, in turn, metabolized by a “killer” enzyme known as fructinase C. This enzyme actually leads to energy loss in the cell and is thought to play a role in numerous diseases, including kidney disease and injury.

Dr. Johnson explains:

” … when fructose is metabolized by fructokinase, the fructose is so rapidly metabolized that there is an initial loss of energy in the cell before energy is produced … Fructokinase is like a run-away train, or a speeding truck coming down the mountain that is out of control. The degree of cell shock induced by fructokinase will relate to the amount of fructose it sees and the level of fructokinase present in the cell. … Sugar Cane Kidney Disease may be another disease of fructokinase. Severe dehydration can activate the polyol pathway that will convert glucose to fructose and provide ammunition for fructokinase to cause injury to the tubules.”

Are the Central American Workers Just More Victims of the Sugar Industry?

Interestingly, World Bank, which has issued more than $100 million in loans to Nicaragua’s sugar industry,^v is funding the Boston University project, with Brooks as the principal investigator, to search for causes of the long-term epidemic of chronic kidney disease in Nicaragua. Nicaragua Sugar Estates Limited, the largest employer in the area and owner of many of the plantations where the illnesses are occurring, denies any connection to the epidemic, which isn’t surprising.

The sugar industry is a shrewd, savvy, well-oiled machine that is also denying any connection between their product and the obesity and diabetes epidemics going on in the industrialized world. They also have access to immense power and give generously to both political parties in the United States to ensure that their products are protected.

While sugar consumption continues to contribute to premature deaths in the developed world in the form of an untold number of cases of cancer, heart disease, high blood pressure, diabetes and other chronic diseases, the Central American workers on the sugar plantations may be victims in another sense, succumbing to kidney disease from years of hard labor, dehydration, and fructose ingestion — or a mix of these and other factors combined.

REFERENCES

• ⁱ Fox News Latino February 21, 2011
• ⁱⁱ iWatch News December 12, 2011
• ⁱⁱⁱ Final Scoping Study Report, Epidemiology of Chronic Kidney Disease in Nicaragua, December 2009 (PDF)
• ^iv BeyondPesticides.org
• ^v iWatch News December 12, 2011