Nitric Oxide Benefits and Side Effects

Written by Dr. Steve Chaney on . Posted in current health articles, Food and Health, Nutritiion, Supplements and Health

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Author: Dr. Stephen Chaney

 

Nitric oxide has had a meteoric rise from obscurity to fame in just a few short years. It’s an amazing story. After all, nitric oxide is a colorless, odorless gas. Who could have known it was destined for greatness? In this article, we will discuss nitric oxide benefits and side effects.

Its rise to fame started in the 1980’s when scientists from several universities discovered that nitric oxide was an important regulator of numerous physiological processes. Just a few years later in 1992 Science magazine named it “Molecule of the Year”, a very prestigious honor. And, in 1998 three of its co-discoverers received the Nobel Prize for their ground-breaking research.

The Benefits of Nitric Oxide

Proven Benefits

Perhaps the most important benefit of nitric oxide is its role in maintaining the health of the endothelial cells that form the inner lining of our blood vessels. Nitric oxide reduces:

  • Platelet aggregation
  • Damage & inflammation of the endothelial cells
  • Oxidation of LDL cholesterol
  • Growth of smooth muscle cells.

This is important because these are the very physiological processes that, if left unchecked, can lead to atherosclerosis and disease of the cardiovascular system (Davignon and Ganz, Circulation, 109: 1127-1132, 2004; Tousoulis et al, Current Vascular Pharmacology, 10: 4-18, 2012).

cardiovascular-system

However, the effect of nitric oxide that has gotten the most attention is its ability to relax the smooth muscle cells that surround our blood vessels. That leads to increased blood flow, which in turn decreases blood pressure, relieves angina, and even prevents erectile dysfunction (Davignon and Ganz, Circulation, 109: 1127-1132, 2004; Tousoulis et al, Current Vascular Pharmacology, 10: 4-18, 2012).

Possible Benefits

Many people with atherosclerosis, diabetes and hypertension (high blood pressure) have low nitric oxide levels. It’s not known whether this is a cause or a result of these diseases, but low nitric oxide levels certainly could contribute to the progression and health consequences of all three diseases. We already know that increasing nitric oxide levels can reduce high blood pressure. It is not yet known whether increasing nitric oxide levels could reduce or reverse heart disease and the effects of diabetes, but this is an area of active research.

Nitric oxide is a neurotransmitter and is thought to play a critical role in memory and learning. It also plays a critical role in immune function. In addition, it enhances the metabolic activity of mitochondria, which could enhance cellular metabolism. The physiological significance of these observations is unknown, but this is another area of active research

Finally, because nitric oxide stimulates blood flow, which should increase oxygen and nutrient delivery to active muscle, it has been suggested that nitric oxide supplements would improve sports performance. The results of clinical studies to test this hypothesis have been mixed. The latest research suggests that nitric oxide supplements may enhance performance in untrained or moderately trained subjects, but not in highly trained subjects (Bescoe et al, Sports Medicine, 42: 99-117, 2012). At last, a sports supplement for the common man!

Drugs That Affect Nitric Oxide Levels

Because nitric oxide has such powerful physiological effects, the pharmaceutical industry has been busy creating drugs that either increase nitric oxide levels or increase the biological effectiveness of nitric oxide. For example, these include drugs to treat angina, hypertension, pulmonary hypertension and erectile dysfunction.

These drugs are generally effective, but have some drawbacks, namely:

  • They have numerous side effects. For example, just listen to the Viagra or Cialis ads on TV.
  • Some of them lose their biological effectiveness over time, especially the angina medications.

Natural Approaches for Increasing Nitric Oxide Levels

nitratesThere are two natural pathways for generating nitric oxide in the body.

1)     The first pathway is an enzymatic process that oxidizes a nitrogen atom in the amino acid arginine to nitric oxide.

2)     The second pathway is a non-enzymatic process in which naturally occurring nitrates and nitrites are reduced to nitric oxide either by bacteria in the mouth and intestine, or by naturally occurring antioxidants.

Arginine is found in proteins. The best protein sources of arginine are red meat, soy, crustaceans (crab, shrimp & lobster), nuts, spinach and lentils. In addition, you can find arginine supplements and arginine-enriched protein supplements.

The best natural sources of nitrates and nitrites are vegetables, especially spinach, beet root and arugula followed by green leafy vegetable and root vegetables in general. Vegetables provide about 80% of the nitrates and nitrites in the American diet.

Nitrates and nitrites do not appear to have the side effects of the nitic oxide producing drugs. This is probably because their effects on raising nitric oxide levels are slower and more modest, and they do not accumulate in the body.

Interestingly, conventionally grown vegetables are higher in nitrates than organically grown vegetables because of the use of inorganic, nitrate-containing fertilizers. However, that doesn’t mean that I recommend conventionally grown produce over organic produce. In last week’s “Health Tips From the Professor”, I reported that conventionally grown produce is 4-fold higher in pesticides.

Red meat and processed meats are also a minor source of nitrates and nitrites in the American diet because nitrates and nitrites are used as preservatives and coloring agents in those meats.

Are Nitrates and Nitrites Beneficial?

Until recently most of the focus has been on arginine as a natural source of nitric oxide. However, there are several lines of evidence suggesting that dietary sources of nitrates and nitrates can also provide the health benefits expected from nitric oxide.

For example, it has long been known that the DASH (Dietary Approaches to Stop Hypertension) diet is as effective as medications for lowering moderately elevated blood pressure. The DASH diet recommends 4-5 servings of vegetables per day, and recent studies have suggested that the nitrates found in those vegetables may play an important role in the blood pressure lowering effect of the DASH diet (Hord et al, American Journal of Clinical Nutrition, 90: 1-10, 2009; Lin et al, Journal of Nutrition and Metabolism, p 472396, 2012).

In addition, a recent meta-analysis of 16 clinical trials concluded that inorganic nitrate and beet root juice supplements lower blood pressure by modest amounts in healthy individuals (Siervo et al, Journal of Nutrition, 143: 818-826, 2013).

Are Nitrates and Nitrites Harmful?

There are two potential concerns around increasing dietary nitrate and nitrite intake.

1)     The one you may have heard the most about is the concern that dietary nitrates and nitrites might increase cancer risk. That turns out to be mainly associated with the nitrates and nitrites added to meats because, in the intestine, nitrites can combine with amino acids to form cancer causing nitrosamines.

That does not appear to be a problem with vegetables because vitamin C and other naturally occurring antioxidants in the vegetables prevent nitrosamine formation. There is no cancer risk in consuming more vegetables.

arginine

2)     The other concern is potential drug-nutrient interactions, especially drugs which also increase nitric oxide levels such as drugs for angina, hypertension, pulmonary hypertension and erectile dysfunction. This is because the combination of nitric oxide from nitrates in the diet and from the drugs has the potential to cause dangerously low blood pressure.

As a general precaution, if you are taking any medications I suggest consulting your doctor or pharmacist before increasing your dietary intake of nitrates and nitrites.

 

The Bottom Line

1)     Nitric oxide plays an important role in keeping the endothelial lining of your blood vessels healthy, which is thought to reduce the risk of atherosclerosis.

2)    Nitric oxide also relaxes the smooth muscle cells that surround our blood vessels. That increases blood flow and decreases blood pressure. The increased blood flow also decreases angina and erectile dysfunction.

3)    Nitric oxide also may increase blood flow to active muscle cells. This has been reported to increase exercise efficiency and sports performance. This effect of nitric oxide appears to primarily affect untrained and moderately trained athletes, not highly trained athletes.

4)    It has been suggested that nitric oxide may be useful for memory and learning, immune function, mitochondrial function and may reduce the risk of diabetes and heart disease. Research is currently going on to evaluate these hypotheses.

5)     There are two natural sources of nitric oxide:

  • The amino acid arginine from proteins and supplements
  • Nitrates and nitrites from vegetables such as spinach, beet root and arugula and from supplements.

6)     Foods (primarily vegetables) and supplements providing dietary nitrates have been shown to modestly lower blood pressure in healthy individuals. They are likely to provide the other benefits associated with nitric oxide as well, without the side effects associated with nitric oxide enhancing medications.

7)     Nitrates and nitrites from vegetables are unlikely to increase cancer risk because vitamin C and other antioxidants from the vegetables prevent the conversion of nitrates and nitrites to nitrosamines.

8)     If you are taking any medications, especially medications for angina, high blood pressure or erectile dysfunction, consult with your doctor or pharmacist before increasing your dietary nitrate intake.

9)     High blood pressure is a silent killer. You should never substitute dietary nitrates for blood pressure medication. Always consult with your physician first. They may be willing to work with you to lower the amount of medication if appropriate. Finally, even if you don’t have high blood pressure, you should monitor your blood pressure on a regular basis. High blood pressure can sneak up on you without you realizing it.

 

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

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Comments (2)

  • Josephine Dye

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    thanks for all you are teaching us about our health

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  • Club Pump

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    Appreciation to my father who shared with me about this weblog,
    this blog is in fact remarkable.

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Latest Article

A Low Carb Diet and Weight Loss

Posted January 15, 2019 by Dr. Steve Chaney

Do Low-Carb Diets Help Maintain Weight Loss?

Author: Dr. Stephen Chaney

 

low carb dietTraditional diets have been based on counting calories, but are all calories equal? Low-carb enthusiasts have long claimed that diets high in sugar and refined carbs cause obesity. Their hypothesis is based on the fact that high blood sugar levels cause a spike in insulin levels, and insulin promotes fat storage.

The problem is that there has been scant evidence to support that hypothesis. In fact, a recent meta-analysis of 32 published clinical studies (KD Hall and J Guo, Gastroenterology, 152: 1718-1727, 2017 ) concluded that low-fat diets resulted in a higher metabolic rate and greater fat loss than isocaloric low-carbohydrate diets.

However, low-carb enthusiasts persisted. They argued that the studies included in the meta-analysis were too short to adequately measure the metabolic effects of a low-carb diet. Recently, a study has been published in the British Medical Journal (CB Ebbeling et al, BMJ 2018, 363:k4583 ) that appears to vindicate their position.

Are low carb diets best for long term weight loss?

Low-carb enthusiasts claim the study conclusively shows that low-carb diets are best for losing weight and for keeping it off once you have lost it. They are saying that it is time to shift away from counting calories and from promoting low-fat diets and focus on low-carb diets instead if we wish to solve the obesity epidemic. In this article I will focus on three issues:

  • How good was the study?
  • What were its limitations?
  • Are the claims justified?

 

How Was The Study Designed?

low carb diet studyThe investigators started with 234 overweight adults (30% male, 78% white, average age 40, BMI 32) recruited from the campus of Framingham State University in Massachusetts. All participants were put on a diet that restricted calories to 60% of estimated needs for 10 weeks. The diet consisted of 45% of calories from carbohydrate, 30% from fat, and 25% from protein. [So much for the claim that the study showed low-carb diets were more effective for weight loss. The diet used for the weight loss portion of the diet was not low-carb.]

During the initial phase of the study 161 of the participants achieved 10% weight loss. These participants were randomly divided into 3 groups for the weight maintenance phase of the study.

  • The diet composition of the high-carb group was 60% carbohydrate, 20% fat, and 20% protein.
  • The diet composition of the moderate-carb group was 40% carbohydrate, 40% fat, and 20% protein.
  • The diet composition of the low-carb group was 20% carbohydrate, 60% fat, and 20% protein.

Other important characteristics of the study were:

  • The weight maintenance portion of the study lasted 5 months – much longer than any previous study.
  • All meals were designed by dietitians and prepared by a commercial food service. The meals were either served in a cafeteria or packaged to be taken home by the participants.
  • The caloric content of the meals was individually adjusted on a weekly basis so that weight was kept within a ± 4-pound range during the 5-month maintenance phase.
  • Sugar, saturated fat, and sodium were limited and kept relatively constant among the 3 diets.

120 participants made it through the 5-month maintenance phase.

 

Do Low-Carb Diets Help Maintain Weight Loss?

low carb diet maintain weight lossThe results were striking:

  • The low-carb group burned an additional 278 calories/day compared to the high-carb group and 131 calories/day more than the moderate-carbohydrate group.
  • These differences were even higher for those individuals with higher insulin secretion at the beginning of the maintenance phase of the study.
  • These differences lead the authors to hypothesize that low-carb diets might be more effective for weight maintenance than other diets.

 

What Are The Pros And Cons Of This Study?

low carb diet pros and consThis was a very well-done study. In fact, it is the most ambitious and well-controlled study of its kind. However, like any other clinical study, it has its limitations. It also needs to be repeated.

The pros of the study are obvious. It was a long study and the dietary intake of the participants was tightly controlled.

As for cons, here are the three limitations of the study listed by the authors:

#1: Potential Measurement Error: This section of the paper was a highly technical consideration of the method used to measure energy expenditure. Suffice it to say that the method they used to measure calories burned per day may overestimate calories burned in the low-carb group. That, of course, would invalidate the major findings of the study. It is unlikely, but it is why the study needs to be repeated using a different measure of energy expenditure.

#2: Compliance: Although the participants were provided with all their meals, there was no way of being sure they ate them. There was also no way of knowing whether they may have eaten other foods in addition to the food they were provided. Again, this is unlikely, but cannot be eliminated from consideration.

#3: Generalizability: This is simply an acknowledgement that the greatest strength of this study is also its greatest weakness. The authors acknowledged that their study was conducted in such a tightly controlled manner it is difficult to translate their findings to the real world. For example:

  • Sugar and saturated fat were restricted and were at very similar levels in all 3 diets. In the real world, people consuming a high-carb diet are likely to consume more sugar than people in the other diet groups. Similarly, people consuming the low-carb diet are likely to consume more saturated fat than people in the other diet groups.
  • Weight was kept constant in the weight maintenance phase by constantly adjusting caloric intake. Unfortunately, this seldom happens in the real world. Most people gain weight once they go off their diet – and this is just as true with low-carb diets as with other diets.
  • The participants had access to dietitian-designed prepared meals 3 times a day for 5 months. This almost never happens in the real world. The authors said “…these results [their data] must be reconciled with the long-term weight loss trials relying on nutrition education and behavioral counseling that find only a small advantage for low carbohydrate compared with low fat diets according to several recent meta-analyses.” [I would add that in the real world, people do not even have access to nutritional education and behavioral modification.]

 

low carb diet and youWhat Does This Study Mean For You?

  • This study shows that under very tightly controlled conditions (dietitian-prepared meals, sugar and saturated fat limited to healthy levels, calories continually adjusted so that weight remains constant) a low-carb diet burns more calories per day than a moderate-carb or high-carb diet. These findings show that it is theoretically possible to increase your metabolic weight and successfully maintain a healthy weight on a low-carb diet. These are the headlines you probably saw. However, a careful reading of the study provides a much more nuanced viewpoint. For example, the fact that the study conditions were so tightly controlled makes it difficult to translate these findings to the real world.
  • In fact, the authors of the study acknowledged that multiple clinical studies show this almost never happens in the real world. These studies show that most people regain the weight they have lost on low-carb diets. More importantly, the rate of weight regain is virtually identical on low-carb and low-fat diets. Consequently, the authors of the current study concluded “…translation [of their results to the real world] requires exploration in future mechanistic oriented research.” Simply put, the authors are saying that more research is needed to provide a mechanistic explanation for this discrepancy before one can make recommendations that are relevant to weight loss and weight maintenance in the real world.
  • The authors also discussed the results of their study in light of a recent, well-designed 12-month study (CD Gardener et al, JAMA, 319: 667-669, 2018 ) that showed no difference in weight change between a healthy low-fat versus a healthy low-carbohydrate diet. That study also reported that the results were unaffected by insulin secretion at baseline. The authors of the current study noted that “…[in the previous study] participants were instructed to minimize or eliminate refined grains and added sugars and maximize intake of vegetables. Probably for this reason, the reported glycemic load [effect of the diet on blood sugar levels] of the low-fat diet was very low…and similar to [the low-carb diet].” In short, the authors of the current study were acknowledging that diets which focus on healthy, plant-based carbohydrates and eliminate sugar, refined grains, and processed foods may be as effective as low-carb diets for helping maintain a healthy weight.
  • This would also be consistent with previous studies showing that primarily plant-based, low-carb diets are more effective at maintaining a healthy weight and better health outcomes long-term than the typical American version of the low-fat diet, which is high in sugar and refined grains. In contrast, meat-based, low-carb diets are no more effective than the American version of the low-fat diet at preventing weight gain and poor health outcomes. I have covered these studies in detail in my book “Slaying The Food Myths.”

Consequently, the lead author of the most recent study has said: “The findings [of this study] do not impugn whole fruits, beans and other unprocessed carbohydrates. Rather, the study suggests that reducing foods with added sugar, flour, and other refined carbohydrates could help people maintain weight loss….” This is something we all can agree on, but strangely this is not reflected in the headlines you may have seen in the media.

The Bottom Line

 

  • A recent study compared the calories burned per day on a low-carb, moderate-carb, and high-carb diet. The study concluded that the low-carb diet burned significantly more calories per day than the other two diets and might be suitable for long-term weight control. If confirmed by subsequent studies, this would be the first real evidence that low-carb diets are superior for maintaining a healthy weight.
  • However, the study has some major limitations. For example, it used a methodology that may overestimate the benefits of a low-carb diet, and it was performed under tightly controlled conditions that can never be duplicated in the real world. As acknowledged by the authors, this study is also contradicted by multiple previous studies. Further studies will be required to confirm the results of this study and show how it can be applied in the real world.
  • In addition, the kind of carbohydrate in the diet is every bit as important as the amount of carbohydrate. The authors acknowledge that the differences seen in their study apply mainly to carbohydrates from sugar, refined grains, and processed foods. They advocate diets with low glycemic load (small effects on blood sugar and insulin levels) and acknowledge this can also be achieved by incorporating low-glycemic load, plant-based carbohydrates into your diet. This is something we all can agree on, but strangely this is not reflected in the headlines you may have seen in the media.
  • Finally, clinical studies report averages, but none of us are average. When you examine the data from the current study, it is evident that some participants burned more calories per hour on the high-carb diet than other participants did on the low carb diet. That reinforces the observation that some people lose weight more effectively on low-carb diets while others lose weight more effectively on low-fat diets. If you are someone who does better on a low-carb diet, the best available evidence suggests you will have better long-term health outcomes on a primarily plant-based, low-carb diet such as the low-carb version of the Mediterranean diet.

For more details read the article above.

 

 

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.

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