Soy and Breast Cancer

soy and breast cancerThe Soy Controversy

Author: Dr. Stephen Chaney

 

 

Soy and breast cancer: the wars are heating up again. You may have seen the recent headlines saying: “Soy protein found to speed the growth of breast cancer!” “Eating soy may turn on genes linked to [breast] cancer growth!” “Women with breast cancer should avoid high soy diets!” It all sounds pretty scary.

If this is true, it is big news. In recent years the consensus in the scientific community has been that soy is not harmful for women with breast cancer, and that it might even be beneficial. However, some skeptics have never accepted that consensus view. Those skeptics are once again claiming that soy protein may be risky for women with breast cancer.

Let’s look at the study behind the recent headlines and see if it is compelling enough to challenge the prevailing consensus on the safety of soy for women with breast cancer.

Does Soy Protein Turn On Breast Cancer Growth Genes?

This study (Shike et al, Journal of the National Cancer Institute, Sep 4 2014, doi: 10.1093/jnci/dju 189) looked at 140 women (average age 56) with invasive breast cancer. They were randomly divided into two groups of 70 and either given soy protein or a placebo between the initial biopsy and the time that surgery was performed to remove the tumor (a period of 7 to 30 days). A second biopsy was obtained at the time of surgery.

The activity of a number of genes associated with breast cancer survival was measured in the two biopsy samples. The observation that made the headlines was:

  • For some of the women in the study the activity of several genes associated with breast cancer growth and survival was increased in the group consuming soy protein compared to the placebo group. The authors concluded: “These data raise concern that soy may exert a stimulatory effect on breast cancer in a subset of women.”

What Are The Limitations Of The Study?

The authors acknowledged the many limitations of the study, but the press has largely ignored them.

  • The increased activity of the cancer growth genes was only seen in 20% of the women studied. For 80% of the women studied soy protein consumption had no effect on the activity of genes associated with breast cancer growth and survival.
  • This effect was only seen for some of the genes associated with breast cancer growth and survival. Other breast cancer growth genes were not affected in any of the women enrolled in the study. The authors conceded that it was unknown whether these limited genetic changes would have any effect on tumor growth and survival.
  • There was no effect of soy consumption on actual tumor growth in any of the women studied.
  • This was a very short term study so it is not known whether these changes in gene expression would have continued if soy supplementation were continued for a longer period of time. There are numerous examples in the literature of initial changes in gene expression in response to a radical change in diet that disappear once the body becomes accustomed to the new diet.
  • There is absolutely no way of knowing if the observed changes in gene expression would actually affect clinical outcomes such as survival, response to chemotherapy or tumor recurrence.

Should Women With Breast Cancer Avoid Soy?breast cancer prevention

Even with all of the limitations listed above, if this were the only study to test the soy-breast cancer hypothesis, I and most other experts would probably be warning women with breast cancer to be very cautious about consuming soy.

However, as I discussed in a previous “Health Tips From the Professor” (https://www.chaneyhealth.com/healthtips/soy-and-breast-cancer-recurrence/) at least five clinical studies have been published on the effects of soy consumption on the recurrence of breast cancer in women who are breast cancer survivors, both in Chinese and American populations. The studies have shown either no effect of soy on breast cancer recurrence or a protective effect. None of them have shown any detrimental effects of soy consumption by breast cancer survivors.

A meta-analysis of all 5 studies was published last year (Chi et al, Asian Pac J Cancer Prev., 14: 2407-2412, 2013). This study combined the data from 11,206 breast cancer survivors in the US and China. Those with the highest soy consumption had a 23% decrease in recurrence and a 15% decrease in mortality from breast cancer.

Another meta-analysis of 18 clinical studies found that soy slightly decreases the risk of developing breast cancer in the first place (J Natl Cancer Inst, 98: 459-471, 2006). To date there is absolutely no clinical evidence that soy increases the risk of breast cancer.

The Bottom Line

What does this mean for you if you are a woman with breast cancer, a breast cancer survivor or someone who is concerned about your risk of developing breast cancer?

  1. The study that has generated the recent headlines has so many limitations that I would not recommend any changes in soy consumption at present. It raises an interesting hypothesis that requires further study and validation. If this hypothesis holds up it may result in changes in dietary recommendations for a very small subset of women with invasive breast cancer.
  1. There are many reasons to include soy protein foods as part of a healthy diet. Soy foods are one of the highest quality vegetable protein sources and provide a great alternative to many of the high fat, high cholesterol animal proteins in the American diet.
  1. I personally feel that these studies are clear cut enough that women who are concerned about their breast cancer risk, women with breast cancer, and breast cancer survivors no longer need to fear soy protein as part of a healthy diet.
  1. The responsible websites agree with this assessment. For example, WebMD and the American Institute for Cancer Research (AICR) both say that breast cancer survivors need no longer worry about eating moderate amounts of soy foods.
  1. The irresponsible websites (I won’t name names, but you know who they are) are still warning breast cancer survivors to avoid soy completely. They are citing the latest study, with all of its limitations, as proof that they were right all along. As a scientist I really have a problem with people who are unwilling to change their opinions in the face of overwhelming scientific evidence to the contrary.
  1. Finally, I want to emphasize that the published studies merely show that soy does not increase the risk of breast cancer and is safe to use for breast cancer survivors. None of those studies suggest that soy is an effective treatment for breast cancer. The protective effects of soy are modest at best. If you have breast cancer, consult with your physician about the best treatment options for you.

 

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.

Is Omega-3 Uptake Gender Specific?

Do We Need To Reexamine Everything We Thought We Knew About Omega-3s?

Author: Dr. Stephen Chaney

is omega-3 uptake gender specific

Some of you may remember the book from a few years ago titled “Men are from Mars, Women are from Venus”. The book proposed that men and women communicate differently (Who would have guessed?), and understanding that fact would help husbands and wives communicate with each other more effectively. I know that some people complained that it was an overly simplistic viewpoint, but I know it sure helped me communicate more effectively with my wife.

I came across a very interesting article recently that suggested the omega-3 fatty acid EPA might be metabolized and utilized differently by men and women. You might say that the statement “Men are from Mars, Women are from Venus” applies to omega-3 utilization as well.

The Science Behind the Study

Now that I’ve captured your interest, perhaps I should fill in a few details. We have known for years that the long chain omega-3 fatty acids EPA and DHA appear to be beneficial at reducing the risk of heart disease. There are several mechanisms for that protective effect:

  1. Omega-3s reduce the stickiness of platelets so that platelet aggregation, a fancy name for blood clotting, occurs less readily. Of course, we want our blood to clot when we cut ourselves, but we don’t want it to clot inside our arteries, because that is the very process that can lead to heart attacks and stroke.
  1. Omega-3s lower triglycerides and reduce inflammation, two important risk factors for heart disease.
  1. Omega-3s help keep the walls of our blood vessels elastic, which enhances blood flow and reduces the risk of hypertension.

However, for any of those things to occur, the omega-3 fatty acids must first be incorporated into our cell membranes. Thus, it is not just how much omega-3s we get in our diet that is important. We need to know how many of those omega-3s are actually incorporated into our membranes.

What if the efficiency of omega-3 uptake into cellular membranes were different for men and women? That would change everything. It would affect the design of omega-3 clinical studies. It would affect omega-3 dietary recommendations for men and women. The implications of gender-specific uptake of omega-3s would be far reaching.

Is Omega-3 Uptake Gender Specific?omega-3

The authors of this week’s study (Pipingas et al., Nutrients, 6, 1956-1970, 2014) hypothesized that efficiency of omega-3 uptake might differ in men and women. They enrolled 160 participants in the study (47% male and 53& female) with an average age of 59 years. The study excluded anybody with pre-existing diabetes or heart disease and anybody who was significantly overweight. The study also excluded anyone taking drugs that might mask the effects of the omega-3 fatty acids and anybody who had previously consumed fish oil supplements or more than two servings of seafood per week.

This was a complex study. In this review I will focus only on the portion of the study relevant to the gender specificity of omega-3 uptake. For that portion of the study, both male and female participants were divided into three groups. The first group received 3 gm of fish oil (240 mg EPA and 240 mg DHA); the second group received 6 gm of fish oil (480 mg EPA and 480 mg of DHA); and the third group received sunflower seed oil as a placebo. The study lasted 16 weeks, and the incorporation of omega-3 fatty acids into red blood cell membranes was measured at the beginning of the study and at the end of 16 weeks.

When they looked at men and women combined, they found:

  • A dose specific increase in EPA incorporation into red cell membranes compared to placebo. That simply means the amount of EPA that ended up in the red blood cell membrane was greater when the participants consumed 6 gm of fish oil than when they consumed 3 gm of fish oil.
  • Very little incorporation of DHA into red blood cell membranes was seen at either dose. This was not unexpected. Previous studies have shown that EPA is preferentially incorporated into red cell membranes. Other tissues, such a neural tissue, preferentially incorporate DHA into their membranes.

When they looked at men and women separately, they found:

  • The efficiency of EPA incorporation into red cell membranes compared to placebo was greater for women than for men. In women increased EPA uptake into red cell membranes was seen with both 3 gm and 6 gm of fish oil. Whereas, with men increased EPA incorporation into red cell membranes was only seen at with 6 gm of fish oil.

What Is The Significance Of These Observations?

The authors concluded “This is an important area for future research because dietary recommendations around long chain omega-3 polyunsaturated fatty acid intake may need to be gender specific.”

However, there are a number of weaknesses of this study:

  1. It was a very small study. Obviously, this study needs to be repeated with a much larger cohort of men and women.
  1. This study was just looking at incorporation of omega-3s into red cell membranes. We don’t yet know whether the specificity of omega-3 uptake will be the same for other tissues. Nor do we know whether there will be gender specificity in the biological effects of omega-3s.
  1. Most importantly, not all previous studies have reported the same gender specificity in omega-3 uptake seen in this study.

So what does this mean for you? Should men be getting more omega-3 fatty acids in their diet than women, as the authors suggested? That is an intriguing idea, but based on the weaknesses I described above, I think it’s premature to make this kind of recommendation until these results have been confirmed by larger studies.

The Bottom Line

  1. A recent study has suggested that women may be more efficient at incorporating the omega-3 fatty acids EPA into their cellular membranes than men. The authors of the study concluded that “…dietary recommendations around long chain omega-3 polyunsaturated fatty acid intake may need to be gender specific.”
  1. However, the study has a number of weaknesses:
  • It was a very small study. Obviously, it needs to be repeated with a much larger cohort of men and women.
  • This study was just looking at incorporation of omega-3s into red cell membranes. We don’t yet know whether the specificity of omega-3 uptake will be the same for other tissues. Nor do we know whether there will be gender specificity in the biological effects of omega-3s.
  • Most importantly, not all previous studies have reported the same gender specificity in omega-3 uptake seen in this study.
  1. The idea that men and women may differ in their needs for omega-3 fatty acids is intriguing, but based on the weaknesses described above, it is premature to make this kind of recommendation until the results of the current study have been confirmed by larger studies.

 

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.

Best Diet For Weight Loss

The Diet Wars Heat Up Again

Author: Dr. Stephen Chaney

best diet for weight loss

What is the best diet for weight loss? One week the headlines say that low-carbohydrate diets are better. The next week it’s low-fat diets that are better. There is even the occasional headline proclaiming that it doesn’t matter which diet you follow as long as you control your calories. It is no wonder that you are confused.

It is unusual, however, to have conflicting headlines within the same week, but that is exactly what happened last week. Let me take you behind the headlines to the actual clinical studies and help you sort through the conflicting headlines.

Are Low-Carbohydrate Diets Best For Weight Loss?

The manuscript behind this headline was published September 2nd in the Annals of Internal Medicine (Bazzano et al, Annals of Internal Medicine, 161: 309-318, 2014). This study was designed to determine which was the best diet for weight loss, low carb diet or low fat diet. The study recruited 148 overweight participants (mean age, 46.8, 88% female, 51% black) and randomly assigned them to either a low-fat diet or low-carbohydrate diet.

The participants on the low-fat diet were instructed to consume <30% of their calories from fat, while the participants on the low-carbohydrate diet were told to limit carbohydrates to <40 g/day. Neither group was told to limit calories. They met with a dietitian 10 times during the 12-month study and received information on dietary fiber (target = 25 g/day) and healthy fats (target = <7% saturated fat and little or no trans fats).

At the end of 12 months the low-carbohydrate diet resulted in significantly greater…

  • Weight loss (7.7 pounds)…
  • Decrease in triglyceride levels…
  • Increase in HDL cholesterol…
  • Decrease in the ratio of total to HDL Cholesterol…

…than the low-fat diet. In short, the results suggested that the low-carbohydrate diet was not only better than the low-fat diet for weight loss, but that it was also more effective in reducing risk factors for cardiovascular disease.

Case closed, you might be tempted to say. The low carb diet is the best the diet for weight loss. But there have been lots of other studies that have come to the opposite conclusion. So we have to ask the question: “Is this study significantly better than all of the studies that have failed to find any difference between the low-fat and low-carbohydrate diets with respect to weight loss and cardiovascular risk?”

What Are The Strengths & Weaknesses Of the Study?

Strengths of the Study: This was a very well designed study. In particular:

  • Dietitians met with the participants at multiple times during the program to assure adherence to the diet, which was very good.
  • The study utilized multiple dietary recalls, both during the week and on weekends.
  • The study had a diverse population.

Weaknesses of the Study:

  1. The study did not control calories. In fact, the caloric intake was ~160 calories/day greater for the low-fat group than the low-carbohydrate group for at least the first 6 months of the study. low carb dietThat alone would be enough to account for the 7.7 pounds difference in weight loss.The reason for the higher caloric intake of low-fat group is not known. It could be due to the lower palatability of the low-carbohydrate diet. Alternatively, it could be due to the lower satiety of the low-fat diet. It was low in both fat and protein, both of which contribute to satiety (the feeling of fullness after we eat).
  2. The study did not specify the type of carbohydrates consumed. The dietitians instructed the participants on the type of fat they should be eating, but not the type of carbohydrate. That was a significant omission. Diets high in sugars and refined carbohydrates provide less satiety and adversely affect cardiovascular risk factors compared to diets where the carbohydrate comes primarily from fresh fruits, vegetables and legumes.
  3. The study did not control protein intake. In fact, the low-fat group consumed significantly less protein than the low-carbohydrate group. As I pointed out in a previous “Health Tips From the ProfessorHigh Protein Diets and Weight Loss , higher protein intakes are essential for maintaining muscle mass during weight loss. That is important because loss of muscle mass can decrease metabolic rate (the rate at which we burn calories 24 hours a day – even at rest).

The amount of protein consumed by the low-carbohydrate group was close to the amount shown to maintain muscle mass during weight loss, while the amount of protein consumed by the low-fat group was close to the amount associated with loss of muscle mass during weight loss. That was reflected in the results. The low-fat group lost muscle mass while the low carbohydrate group actually gained muscle mass. The resulting difference in muscle probably meant that the low-carbohydrate group was burning more calories on a daily basis than the low-fat group.

In short, this is a good study, but it has important flaws. It is not a game changer.

Do Low-Carbohydrate & Low-Fat Diets Result In Identical Weight Loss?

The study behind this headline was published in the September 3rd edition of the Journal of the American Medical Association (Johnson et al, JAMA, 312: 923-933, 2014). This study was a meta-analysis that combined the results of 48 studies with 7286 participants. When the authors combined the data from all of the published studies there was no difference in weight loss for the low-fat and low-carbohydrate diets over a one or two year period.

The strength of the study is that it combines the results of multiple studies. That increases the statistical power of the observations and smoothes over the effect of outlier studies, such as the one described above. This is the study I would trust.

What Do The Experts Say?

Dr. Walter Willett, Chair of the Department of Nutrition at the Harvard School of Public Health was best diet for weight lossquoted as saying: “…some people [would] do well on either diet. The key issue for each person is finding a way of eating that is healthy and can be maintained for the long term.”

Dr. Bradley Johnson (the author of the meta-analysis) was quoted as saying: “The take home message is that people should choose a diet they can adhere to…”

The Bottom Line

1)  Ignore the recent headlines suggesting that low-carbohydrate diets may be more effective than low-fat diets for weight loss. When you control for calories and protein intake there is no difference between the two diets with respect to long term weight loss.

2)  You can also ignore the headlines telling you that low-carbohydrate diets are better for cardiovascular health. You don’t need to avoid carbohydrates to have a healthy heart. You just need to make healthy carbohydrate choices – fruits, vegetables, legumes and whole grains instead of refined flour products and sugary junk food.

3)  Experts will tell you that the best diet is a healthy diet that you can stick with long term.

4)  My personal recommendations are to avoid extremes (either low-fat or low-carbohydrate). Instead:

  • Aim for moderate amounts of healthy fats and healthy carbohydrates.
  • Don’t ignore protein. Make sure you get enough protein to maintain your muscle mass.
  • Control calories by reducing portion sizes and choosing healthy snacks.

 

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.

Is Alkaline Water Better For You?

Facts About Water

Author: Dr. Stephen Chaney

 

is alkaline water better for youIs alkaline water better for you?  It’s bad enough that some people are paying a premium price for bottled water that isn’t required to be any better than tap water, but the latest fads appear to be things like “alkaline” water and “ionized” water. And these “super” waters come with a really hefty price tag.

If you believed the hype behind these products, you would think that they are revolutionary advances that will cure all sorts of ills. But the truth is these enticing claims are completely bogus. They contradict the basic laws of chemistry and biochemistry.

More importantly, there are no good quality clinical studies showing that they work!

What Is Alkaline Water?

Let’s start with alkaline water – but first a bit of background information.

Pure water has a pH of around 7, which is neutral. However, if the water is exposed to air for any length of time it picks up CO2 from the atmosphere. The CO2 dissolves in the water and is converted to carbonic acid making most sources of pure water slightly acidic.

On the other hand, if metal salts are dissolved in the water it generally becomes slightly alkaline.

Is Alkaline Water Better For You?

Here are some questions you might ask when deciphering if alkaline water is better for you than plain water:

1) What Are the Benefits of Drinking Alkaline Water?

In the 1930s Otto Warburg, one of the founders of modern biochemistry, showed that cancer cells were much more dependent on glucose (blood sugar) as an energy source than were most other cells in the body and that cancer cells metabolized glucose in a way that made the cancer cells very acidic.

That information languished for many years, but interest in the “Warburg Hypothesis” has been revived in recent years by studies showing that cancer cells can be selectively killed by limiting their source of glucose.

So, what are the benefits of drinking alkaline water?  In theory, making the body more alkaline would also slow the growth of the cancer cells. There is some evidence to support that hypothesis, but the evidence is still relatively weak.

It is the same with the other proposed health benefits of alkalinizing the body. There is some evidence in the literature, but it is not yet convincing. As a scientist I’m keeping an open mind, but I’m not ready to when-pigs-fly“bet the farm” on it.

2) Can Alkaline Water Alkalinize the Body?

Here the answer is a clear cut NO! In fact, this hypothesis wins my “Flying Pig” award for the month!

The body has a very strong buffer system and some elaborate metabolic controls to maintain a near-constant neutral pH. More importantly, water is such a weak buffer that it has almost no effect on body pH!

Alkaline Foods

If you really want to alkalinize your body you can do that by eating more of the alkaline foods (most fruits, including citrus fruits, and most vegetables, peas, beans, lentils, seeds & nuts) and less of the acidic foods (grains, especially refined grains, meat, especially red meat, fish, poultry and eggs).

I’ve seen some experts recommend 60% alkaline foods and 40% acidic foods. I can’t vouch for the validity of that recommendation in terms of the benefits of alkalinizing the body, but there are lots of other good reasons to eat more fresh fruits and vegetables and less red meat and refined carbohydrates.

Is Ionized Water Beneficial?

Ionized water is an even sillier concept from a chemical point of view.

It is very difficult to ionize pure water and the ions that you do create quickly recombine to give you pure water again without any change in pH or physical properties.

If you add sodium chloride (table salt) to the water you can get electrolysis that creates a slightly alkaline pH at one electrode and a slightly acidic pH at the other electrode.

However, as soon as you turn off the current, these pH changes rapidly disappear. Even if you were somehow able to capture some of the alkaline or acidic water remember that water alone has almost no effect on body pH.

Never Underestimate The Placebo Effect

But, what about all of those glowing testimonials that you have heard?

You need to remember that the placebo effect is near 50% when it comes to pain or a feeling of well being.

You can’t repeal the laws of chemistry and biochemistry. Water is, after all, just water!

Good science trumps good testimonials any day.  Never, never underestimate the placebo effect.

The Bottom Line

Don’t waste your money on alkaline water or ionized water. Water is a very poor buffer and has almost no effect on the pH of our bodies.

There may be some health benefits to keeping our bodies in a more alkaline state, but the best way to do that is to eat more alkaline foods and less acid foods (http://www.webmd.com/diet/alkaline-diets).

 

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.

Do Omega-3s Slow Cognitive Decline?

Why Omega-3s Should Be Part Of Your Holistic Brain Health Program

Author: Dr. Stephen Chaney

 

Omega3-Cognitive-DeclineWho wouldn’t want to avoid dementia and Alzheimer’s in our later years? There is a ton of advice on the internet about “magic” solutions to keep our brains sharp well into our 90s. Unfortunately, most of that advice is contradicted by other claims on the internet that those solutions don’t work. What should a person do if they want to keep their brain healthy?

Two weeks ago I talked about a study showing that a holistic approach, which to me includes healthy diet, weight control, exercise, supplementation, socialization and memory training, significantly reduces cognitive decline in the elderly (Is There Hope For Alzheimer’s?).

Last week I sorted out the conflicting advice about B vitamins and cognitive decline (Do B Vitamins Slow Cognitive Decline?). More importantly, I told you who would benefit from B vitamin supplementation and who would not.

In part three of this series I’m going to help you sort out the conflicting information on omega-3s and cognitive decline. Then I will sum up what a holistic brain health program might look like for you.

Why Might Omega-3s Slow Cognitive Decline?

There are lots of reasons to believe that omega-3 fatty acids are important for brain health and might, therefore, slow cognitive decline. For example:

Omega-3 fatty acids improve blood flow to the brain.

The omega-3 fatty acid DHA is an important part of the myelin sheath, the protective coating for every neuron in our body.

DHA is also converted to a neuroprotective agent that protects the brain from oxidative stress.

The Confusing Evidence About Omega-3s And Cognitive Decline

The data about omega-3s and cognitive function to date have been confusing. Most observational studies have reported better cognitive functioning and lower incidence of Alzheimer’s disease in populations that consume large amounts of fatty fish rich in omega-3s. There is also some evidence that omega-3 supplementation improves cognitive function for patients with mild cognitive impairment or very mild Alzheimer’s disease. However, most short-term, randomized, placebo-controlled studies have found no effect of omega-3 supplementation on cognitive functioning for patients who already have mild to moderate Alzheimer’s disease.

It had been assumed for years that by the time one already had Alzheimer’s it was too late for omega-3s to exert a protective effect. However, some recent studies have suggested a possible genetic explanation for the conflicting information on omega-3s and cognitive decline.

There is a genetic variant of the ApoE gene called ApoE4 that dramatically increases the risk of Alzheimer’s disease. Around 20-25% of the general population and 40-50% of Alzheimer’s patients have this genotype. Several recent studies have suggested that omega-3s may protect against cognitive decline only in people who do not carry the ApoE4 genotype. The current study (Daiello et al, Alzheimer’s & Dementia, doi: 10.1016/j.jalz.2014.02.005) was designed to test this hypothesis.

Do Omega-3s Slow Cognitive Decline?

This was a very well designed study. The investigators enrolled 819 older adults (average age 75, range 55-90) in the study and followed them for 3 to 4 years. 229 of the participants had normal cognition at enrollment, 337 had mild cognitive impairment and 193 had Alzheimer’s disease. All participants were tested for ApoE genotype.

The study participants were tested at baseline and every 6 months with two tests of cognitive function – the Alzheimer’s Disease Assessment Scale (ADAS) and the fish-oil-benefitsMini-Mental State Examination (MMSE). MRI tests were also done at baseline and every 6 months to assess brain volume.

The participants were asked about fish oil supplement use at each of those times. Only those who reported taking fish oil supplements at every examination were considered fish oil supplement users (117), and only those who never consumed fish oil supplements were considered non-users (682).

The results were pretty interesting:

  • Fish oil supplements significantly decreased cognitive decline and brain shrinkage in the ApoE4 negative population, but not in the ApoE4 positive population.
  • The beneficial effects of fish oil supplementation were only seen in the population with normal cognition at the time the study started. Those benefits were not significant in the populations with mild cognitive impairment or Alzheimer’s disease.
  • Unfortunately, the study was not large enough to perform a statistic analysis of the ApoE positive and negative subpopulations of the groups with mild cognitive impairment or Alzheimer’s disease, so it was not possible to tell whether omega-3s might have been beneficial in people with mild cognitive impairment or Alzheimer’s disease who are ApoE4 negative.

The authors concluded that their results “highlight the need for future research on the effects of long-term fish oil supplement use on cognitive aging and dementia prevention in middle-aged and older adults”.

They also highlighted a major reason why so many previous studies have failed to find a link between omega-3s and cognitive decline when they said “Studies on cognitive aging that don’t screen subjects for ApoE4 are doomed to failure”.

Putting It All Together: Holistic Approaches For Preserving Brain Health

When I began this series three weeks ago with Is There Hope For Alzheimer’s? , I talked about the importance of holistic approaches. I referred back to a cancer expert who said that he could prove that a holistic lifestyle approach significantly reduced the risk of colon cancer, but he couldn’t prove that any individual lifestyle change had any effect on colon cancer risk.

holistic-health-programThe situation is very similar when we talk about preserving cognitive function. Over the past three weeks I have identified many things that can reduce the risk of cognitive decline – healthy diets, exercise, socialization, mental exercise, maintaining a healthy weight, B vitamins and omega-3 fatty acids. If we follow a holistic lifestyle that combines all of these things, we are likely to dramatically increase our probability of maintaining a healthy brain well into our golden years.

However, holistic lifestyle changes are difficult. I know some of you will want to take a simpler approach. You are going to ask:

1)  Are there some individual lifestyle changes that are certain to slow cognitive decline on their own?

The answer is probably not. Maintaining a healthy weight comes close. However, some evidence suggests that it is not obesity itself that increases the risk of dementia. It is the insulin resistance and elevated blood sugar associated with obesity – and not everyone with obesity has insulin resistance and elevated blood sugar levels. So for some people obesity may not increase their risk of dementia. For those people weight loss might not reduce their risk of dementia.

2)  Are there some lifestyle changes I don’t need to make if my diet is OK?

The study I described in last week’s Health Tips From the Professor  found that B vitamin supplementation only reduced the risk of cognitive decline for people who were B vitamin deficient.

So one might assume that you could get a simple test for B vitamin deficiency and determine whether B vitamin supplementation would be beneficial or not. But which test should you get? Who is at risk? Is it the 5-10% of the population with elevated homocysteine levels, the 10% of the population with a deficiency of methylenetetrahydrofolate reductase (MTHFR), the 25% of the population with low blood levels of B6 or the 40% of the population over 60 with B12 deficiency? We simply don’t know.

3)  Is it even worth bothering making lifestyle changes if I’m genetically predisposed to developing Alzheimer’s?

This week’s study found that omega-3s reduced the risk of cognitive decline only in people who did not have the ApoE4 genotype. Does that mean that you should rush out and test yourself for ApoE4?

Here the answer is a clear no. In the first place, we have no idea how the ApoE4 genotype affects the other lifestyle changes that slow cognitive decline.

In addition, there is another, very important reason why most experts, including the professor, decline being tested for ApoE4. The ApoE4 genotype dramatically increases your risk of developing Alzheimer’s disease, and there is no proven treatment for reducing that risk if you are ApoE4 positive. Who wants to know that they are at increased risk of developing Alzheimer’s if there is nothing they can do about it?

 

The Bottom Line

1)     This study suggests that supplementation with omega-3s (fish oil) significantly reduces cognitive decline and brain shrinkage in older adults (average age 75).

2)     The effect of fish oil supplementation on cognitive decline and brain shrinkage was only seen in people who lacked the ApoE4 genotype. Fish oil supplementation was ineffective in people who were ApoE4 positive.

3)     The study showed that fish oil supplementation was effective at reducing cognitive decline and brain shrinkage in older adults with normal brain function who were ApoE4 negative, but the study was not large enough to determine whether it was also effective in older adults with cognitive decline or Alzheimer’s disease who were ApoE4 negative. Further research is needed to clarify this important point.

4)     This was a relatively well designed study, but it was a small study. Larger, long-term studies are needed to confirm these results. More importantly, based on the results of this study, future studies will need to screen participants for ApoE4 status to assure that there is a large group of ApoE4 negative participants. This would provide enough statistical power to clearly determine whether fish oil supplementation can also benefit people who already have symptoms of cognitive decline or Alzheimer’s and are ApoE4 negative.

5)     Even though ApoE4 status influences the effectiveness of fish oil supplementation on slowing cognitive decline, you probably don’t want to rush out and get yourself tested for ApoE4. We don’t know whether ApoE4 status influences other lifestyle changes that slow cognitive decline. More importantly, the ApoE4 genotype dramatically increases the risk of developing Alzheimer’s disease, and there is currently no proven treatment for reducing that risk if you are ApoE4. Who wants to know that they are at increased risk of developing Alzheimer’s if there is nothing you they do about it?

6)     Finally, don’t rely solely on supplementation with B vitamins or omega-3s to reduce your risk of cognitive decline. Your chances of reducing cognitive decline are best with a holistic approach that includes healthy diet, exercise, socialization, mental exercises, maintaining a healthy weight, B vitamins and omega-3 fatty acids.

 

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.

Do B Vitamins Slow Cognitive Decline?

The B Vitamin Controversy

Author: Dr. Stephen Chaney

 

cognitive-declineDo B Vitamins slow cognitive decline?  Heart disease, cancer and strokes are all pretty scary. Even if we survive, our quality of life may never be the same. But, we can endure many physical afflictions if our mind stays sharp. For most of us the ultimate irony would be to spend a lifetime taking good care of our body, only to lose our mind.

Last week I told you about a study showing that a holistic approach, which to me includes healthy diet, weight control, exercise, supplementation, socialization and memory training, significantly reduces cognitive decline in the elderly (https://www.chaneyhealth.com/healthtips/hope-alzheimers/).

This week I’d like to focus on one aspect of that holistic approach, namely B vitamins. If you are like most people, you are probably confused about the role of B vitamins in preserving mental function. On the one hand you are seeing headlines proclaiming that B vitamins slow cognitive decline as we age. On the other hand you are being told “Don’t waste your money. B vitamins won’t slow cognitive aging.” What are you to believe?

 

Why Might Certain B Vitamins Slow Cognitive Decline?

To help you understand how B vitamins might slow cognitive decline I’m going to need to get a little biochemical. Don’t worry. I’ll be merciful.

#1: The story starts with a byproduct of amino acid metabolism called homocysteine.

Multiple studies have shown that elevated blood levels of homocysteine are associated with cognitive decline and Alzheimer’s. Elevated homocysteine levels are found in 5-10% of the overall population and elevated homocysteine levels double the risk of Alzheimer’s.

In our bodies homocysteine is converted to the amino acid methionine in a reaction involving folic acid and vitamin B12. Homocysteine is converted to the amino acid cysteine in a reaction involving vitamin B6. Thus, elevated homocysteine levels are most frequently associated with deficiencies of these three B vitamins caused by inadequate intake or increased need for those B vitamins.

#2: Many of us are deficient in the B vitamins that lower homocysteine levels.

There are many situations in which inadequate intake or increased need of those vitamins can occur. For example:

Vitamin B12:

vitamin-B12

  • The most frequent cause of B12 deficiency is the age related loss of the ability to absorb vitamin B12 in the upper intestine. This affects 10-30% of people over the age of 50.
  • Chronic use of acid-suppressing medications such as Prilosec, Nexium, Tagamet, Pepcid and Zantac also decreases B12 absorption and increases the risk of B12 deficiency. Millions of Americans use those drugs on a daily basis.
  • Finally, vegetarians can become B12 deficient because most naturally occurring B12 is found in meat and dairy products.
  • Overall, B12 deficiency has been estimated to affect about 40% of people over 60 years of age.

Folic Acid:

  • In the past, many Americans consumed diets that were low in folic acid. However, this has been minimized in recent years by the fortification of grain products with folic acid. Today, the primary concern is with factors that increase the need for folic acid.
  • For example, birth control pills along with some anti-inflammatory and anticonvulsant medications interfere with folic acid metabolism and increase the need for folic acid.
  • In addition, deficiency of the enzyme methylenetetrahydrofolate reductase (MTHFR) substantially increase the amount of folic acid needed to reduce homocysteine levels to normal. About 10% of the US population has this enzyme deficiency.

Vitamin B6:

  • Birth control pills along with some drugs used to treat high blood pressure and asthma interfere with vitamin B6 metabolism and increase the need for vitamin B6.
  • Vitamin B6 is found in reasonable amounts in meat, beans, green leafy vegetables, brown rice and whole grain flour. Unless you are consuming a balanced diet containing all of those foods your intake of B6 may be inadequate. About 25% of Americans have low blood levels of B6.

#3: Multiple studies have shown that supplementation with folic acid, B12 and B6 can lower homocysteine levels.

Based on this information it has been hypothesized that supplementation with folic acid, B12 and B6 would decrease the rate of cognitive decline in people with elevated homocysteine levels. It is a logical hypothesis, but is it correct?

The Evidence That B Vitamins Don’t Slow Cognitive Decline

The recent headlines saying that B vitamins don’t slow cognitive decline came from a meta-analysis that included the results of 11 clinical trials with 22,000 individuals B-vitamins-cognitive-decline(Clarke et al, American Journal of Clinical Nutrition, 100: 657-666, 2014). That sounds pretty impressive! But to properly assess the conclusions of this study you need to understand the strengths and weaknesses of meta-analyses.

  • The strength of a meta-analysis is pretty obvious. By combining the results of many clinical trials and thousands of patients you greatly increase the statistical power of the study.
  • However, the strength of a meta-analysis is only as good as the studies it includes. It’s the old “GIGO” principle (Garbage In, Garbage Out). If the individual studies are poorly designed, the conclusions of the meta-analysis will be misleading.

Unfortunately, many of the studies in this meta-analysis were poorly designed. They fall into two groupings:

Problem #1: Many of the studies included in the meta-analysis were not designed to test the actual hypothesis.

Remember that the original hypothesis was that supplementation with folic acid, B12 and B6 would decrease the rate of cognitive decline in people who were deficient in those B vitamins and had elevated homocysteine levels. Nobody was predicting that B vitamin supplementation would make any difference for people who already had adequate B vitamin levels and low homocysteine levels.

Five of the studies were not designed to look at that hypothesis at all. They were very large studies designed to look at the hypothesis that B vitamins might reduce the risk heart attack and stroke in patients with cardiovascular disease. Some of those patients had elevated homocysteine levels, but many did not.

It’s no wonder they did not show any significant effect of B vitamins on cognitive decline. They weren’t designed for that purpose, but they contributed the vast majority of patients and most of the statistical weight to the conclusions of the meta-analysis.

Problem #2: Some of the studies were too short to draw any meaningful conclusions.

Three of the studies were well designed in that they specifically looked at patient populations with elevated homocysteine levels and documented B vitamin deficiency, but they only lasted for 3 to 6 months. There simply was not a large enough cognitive decline in the control group in such a short time span for one to see a statistically significant effect of B vitamin supplementation.

Do B Vitamins Slow Cognitive Decline?

B-vitamins-slow-cognitive-declineThat leaves three studies from the original meta-analysis, plus another clinical study published after the meta-analysis was complete, that were actually designed to test the hypothesis and were long enough to give meaningful results. Three of those four studies showed a positive effect of B vitamin supplementation on cognitive function.

Study #1: This study was a 3-year study in patients with elevated homocysteine levels, folic acid deficiency and normal B12 levels (Durga et al, The Lancet, 369: 208-216, 2007). They were given 800 ug/day of folic acid or a placebo. Folic acid levels increased 576% and homocysteine levels decreased by 25%. At the end of 3 years the change in memory, information processing speed and sensorimotor speed was significantly better in the folic acid group than the control group.

Study #2: This was a 2-year study in patients with elevated homocysteine levels (McMahon et al, New England Journal of Medicine, 354: 2764-2769, 2006). B vitamin deficiencies were not measured. The patients were given either 1000 ug 5-methyltetrahydrofolate, 500 ug of B12 and 10 mg of B6 or a placebo. Homocysteine levels decreased significantly, but there was no effect of B vitamins on cognitive function in this study.

Study #3: This study was a 2-year study in patients over 70 with mild cognitive decline (Smith et al, PLoS ONE 5(9): e12244. doi:10.1371/journal.pone.0012244, 2010). B vitamin deficiencies were not measured. The patients were given either 800 ug of folic acid, 500 ug of B12 and 20 mg of B6 or placebo. B vitamin supplementation increased folic acid levels by 270% and decreased homocysteine levels by 22%. Brain volume was measured by MRI. Overall, B vitamin supplementation decreased brain shrinkage by 30%. The rate of brain shrinkage in the placebo group and the protective effect of B vitamins were greatest in the patients with elevated homocysteine at entry into the trial.

Study #4: This was an expansion of the previous study (Douaud et al, Proceedings of the National Academy of Sciences, 110: 9523-9528, 2013). In this study the same investigators focused on the regions of the brain most vulnerable to cognitive decline and the Alzheimer’s disease process. They found that B vitamin supplementation reduced brain atrophy in those regions by 7-fold (a whopping 86% decrease in brain shrinkage) over a 2-year period. Once again, the rate of brain shrinkage in the placebo group and the protective effect of B vitamins were greatest in the patients with elevated homocysteine at entry into the trial.

Are B Vitamins Only Effective In People With Elevated Homocysteine Levels?

The published data certainly suggest that B vitamins may reduce cognitive decline in people with elevated homocsteine levels, but what about other people with B vitamin deficiencies? For reasons that are not entirely clear, not everyone with folic acid, B12 and/or B6 deficiencies has elevated homocsyteinine levels.

Other symptoms of folic acid, B12 and B6 deficiency are depression, pronounced fatigue, irritability, peripheral neuropathy (tingling and loss of feeling in extremities), and loss of fine motor coordination. If you have these symptoms and they are caused by B vitamin deficiency, B vitamin supplementation may relieve the symptoms.

B vitamin supplementation may also slow cognitive decline in individuals who are B vitamin deficient and have normal homocysteine levels, but that hypothesis has not been clinically tested.

The Bottom Line

1)     Forget the headlines telling you that B vitamins don’t slow cognitive decline. Also ignore headlines implying that B vitamins will help everyone be an Einstein well into their 90’s. As usual, the truth is somewhere in between.

2)    Supplementation works best for people with inadequate dietary intake and/or increased needs. That is just as true for B vitamins and brain health as it is for other health benefits of supplementation.

3)     Many people with deficiencies of folic acid, B12 and/or B6 have elevated homocysteine levels. If you do have elevated homocysteine levels, the data are pretty convincing that supplementation with folic acid, B12 and B6 may reduce the risk of cognitive decline. Unfortunately, homocysteine is not something that is routinely measured in most physical exams, but perhaps it should be.

4)     Not everyone with folic acid, B12 and/or B6 deficiencies has elevated homocsyteinine levels. Other symptoms of folic acid, B12 and B6 deficiency are depression, pronounced fatigue, irritability, peripheral neuropathy (tingling and loss of feeling in extremities), and loss of fine motor coordination. If you have these symptoms and the symptoms are caused by B vitamin deficiency, B vitamin supplementation might also slow cognitive decline. However, that hypothesis has never been clinically tested.

5)     It has been recognized recently that deficiencies of methylenetetrahydrofolate reductase (MTHFR) interfere with folic acid metabolism and cause elevated homocysteine levels. Contrary to what you may have heard, 5 methyltetrahydrofolate is not essential for reducing homocysteine levels in people with MTHFR deficiency. High levels of folic acid work just as well for most MTHFR-deficient individuals. [It is also interesting to note that the only well designed clinical study that did not find B vitamins to be effective in reducing cognitive decline was the one that substituted 5-methyltetrahydrofolate for folic acid.]

6)     B vitamin deficiency is common in the elderly due to impaired absorption and the use of multiple medications that interfere with B vitamin metabolism and can contribute to many of the symptoms commonly associated with aging. In this population, B vitamin supplementation is cheap and often effective.

7)     B12 deficiency is common in adults 60 and older. High doses of folic acid alone can mask B12 deficiency and lead to irreversible nerve damage. For that reason high doses of folic acid should be paired with high dose B12 and B12 nutritional status should be determined. [Contrary to what you may have heard, 5-methyltetrahydrofolate is just as likely to mask B12 deficiency as is folic acid.]

8)     Finally, assuring an adequate intake of B vitamins is just one component of a holistic approach for maintaining brain function as long as possible. Other important lifestyle components for preserving cognitive function are healthy diet, weight control, exercise, supplementation, socialization and memory training. (https://www.chaneyhealth.com/healthtips/hope-alzheimers/).

 

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.

Is There Hope for Alzheimer’s

Preventing Cognitive Decline As We Age

Author: Dr. Stephen Chaney

 alzheimer's

As we age nothing is more terrifying than the word Alzheimer’s. For most of us the ultimate irony would be to spend a lifetime taking good care of our body, only to lose our mind. From time to time there are encouraging reports about the potential of low fat diets, diets rich in fruits and vegetables, B vitamins, omega-3 fatty acids, various herbs, and other natural approaches that might slow cognitive decline as we age.

Inevitably, it seems, those hopes are dashed by subsequent meta-analyses supposedly showing that each of those approaches is worthless. That wouldn’t be so bad if there were effective medications to slow cognitive decline and prevent Alzheimer’s, but there aren’t. The Alzheimer’s drugs on the market today simply have not been shown to be effective.

But, what if all of these studies were missing the mark by focusing on individual interventions? Perhaps we should be focusing a holistic approach instead.

 

The Power of Holistic Approaches

One of the examples of the power of a holistic approach that I love to use, because it really made an impression on me as a young scientist, occurred at an International Cancer Symposium I attended more than 30 years ago.

I attended a session in which an internally renowned expert was giving his talk on colon cancer. He said, “I can show you, unequivocally, that colon cancer risk is significantly decreased by a lifestyle that includes a high-fiber diet, a low-fat diet, adequate calcium, adequate B-vitamins, exercise and weight control. But I can’t show you that any one of them, by themselves, is effective.”

The question that came to me as I heard him speak was: “What’s the message that a responsible scientist or responsible health professional should be giving to their patients or the people that they’re advising?” You’ve heard experts saying: “Don’t worry about the fat” “Don’t worry about calcium.” “Don’t worry about B-vitamins.” “Don’t worry about fiber.” “None of them can be shown to decrease the risk of colon cancer.”

Is that the message that we should be giving people? Or should we really be saying what that doctor said many years ago – a lifestyle that includes all of those things significantly decreases the risk of colon cancer?

What about Alzheimer’s and cognitive decline? Could a holistic approach have an impact here as well?

 

Is There Hope For Alzheimer’s?

preventing-cognitive-declineA study performed by Dr. Miia Kivipelto and colleagues at the Karolinska Insitute in Sweden and the National Institute for Health and Welfare in Helsinki, Finland suggests that a holistic approach may, in fact, be able to slow cognitive decline in older people.

Previous studies had suggested that exercise, a good diet, socialization and memory training might slow cognitive decline in the elderly, but, like all other individual interventions, the benefits of these interventions were not reproducible. Dr. Kivipelto and colleagues designed a clinical study that combined all of these interventions into a single holistic approach.

They started with 1,260 healthy adults aged 60-77 from Sweden and Finland and divided them into two groups. One group was enrolled in a holistic program involving exercise, a healthy diet, socialization and memory training. This group was closely monitored for compliance. The other group was just given general health advice – not unlike the advice you might expect to receive from your doctor.

Each group was given a memory test at the beginning of the study and a second memory test two years later. Both groups scored about the same on the first memory test. However, the group enrolled in the holistic program did considerably better on the second memory test than the control group who had just been given general health advice.

One of the lead investigators was quoted as saying: “These findings show that prevention is possible, and it may be good to start early [before the signs of cognitive decline become evident]. With so many negative trials of Alzheimer’s drugs reportedly lately, it’s good that we may have something that everyone can do now to lower their risk [of cognitive decline].”

 

Limitations of the Study

There are two big caveats for this study.

1)     The study was too short to assess the effectiveness of this approach at reducing Alzheimer’s. The investigators plan to continue the study for 7 years. They hope that enough participants will have developed Alzheimer’s by then so they can accurately assess whether this approach is as effective at preventing Alzheimer’s as it is at preventing cognitive decline.

2)     This study was recently presented at an Alzheimer’s Association International Conference. It has not yet undergone the rigorous peer review required for publication. Once the study has been published I will give you an update.

 

The Bottom Line

1)     It has been very difficult to prove that individual interventions, whether they are natural or pharmaceutical, are effective at preventing cognitive decline and the onset of Alzheimer’s as we age.

2)    However, a recent study suggests that a holistic approach that includes exercise, optimal nutrition, socialization and memory training may be effective at preventing cognitive decline in older adults.

3)     Based on previously published individual studies, optimal nutrition probably includes:

  • A diet low in fat, especially saturated fat and trans fats
  • A diet with lots of fresh fruits and vegetables
  • Extra B vitamins, especially with high risk populations
  • Extra omega-3 fatty acids

4)     Although not mentioned in this study, maintaining proper body weight is also an important part of a holistic approach to reducing the risk of cognitive decline. In a previous “Health Tips From the Professor” I shared data showing that obesity alone can cause a 3-fold increase in the risk of developing dementia.

5)    The take home message should not be that each of the natural interventions is ineffective at preventing cognitive decline as we age. Rather, the message should be that a holistic approach that combines all of the natural interventions may be effective at preventing cognitive decline.

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.

Nitric Oxide Benefits and Side Effects

Reverse Heart Disease?reverse-heart-disease

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.

Are Organic Foods Healthier?

Organic Fruits & Vegetables

Author: Dr. Stephen Chaney

 fruits-vegetables

Are organic foods healthier for us than conventionally grown foods, specifically fruits and vegetables? The controversy about the benefits of organically raised produce continues. In fact, about the only thing that all sides agree on is that:

  • Organic foods have lower pesticide and herbicide residues and cause less environmental pollution.
  • Organic foods generally cost more.

But that is where all agreement ends.

  • Some experts argue that the pesticide levels on conventionally grown fruits and vegetables are within safe levels and that any risk from the pesticides is outweighed by the health benefits of the fruits and vegetables themselves.
  • Some studies have suggested that organic foods, fruits and vegetables, are healthier because they have higher antioxidant levels, while other studies have reported no nutritional differences between organic and conventionally grown fruits and vegetables.

Benefits of Organic Food?

The present study (Baranski et al, British Journal of Nutrition, doi: 10.1017/S0007114514001366) tried to overcome the shortcomings of many of the previously published reports.

To begin with this study was a meta-analysis that combined the results from 343 of the best designed previous studies to increase the statistical power of the analysis. In addition, the investigators utilized a type of statistical analysis that was superior to previously published studies. In short, it was a very good study. It does show some benefits of organic food.

organic-farms

The results were fairly clear cut:

  • Pesticide residues were four-fold lower in the organically raised produce than the conventionally raised produce. This result has been consistently seen in all of the previously published studies, and is probably the #1 reason that people choose organic produce. It is also one of the most agreed upon benefits of organic food.
  • Polyphenol antioxidant levels were significantly higher in the organically raised produce. The percent increase ranged from 19% to 69% depending on the polyphenolic compound tested. This increase has not been seen in all previously published studies, but would represent a side benefit if true.
  • Levels of the toxic metal cadmium were significantly less in the organically grown fruits and vegetables. The authors speculated that the cadmium found in conventionally grown produce came from the inorganic fertilizers that were used.

Should You Choose Organic Supplements?

natural-medicine

If organic foods are better for you than conventionally grown foods, does that mean that you should also choose organic supplements? While that idea sounds logical, the reality is actually more complex.

While organic foods clearly have less pesticides and toxic metals than conventionally grown foods, the level of those contaminants is not zero – even in foods with organic certification. The problem is that our environment is so polluted that no farm is contaminant free. A farmer can use the best organic practices, but if their groundwater is contaminated or pesticides from neighboring farms blow on to their farm, some of those toxic residues will end up in their “organic” crops.

 

So with supplements, “Organic” certification is not an absolute guarantee of purity. Instead you should insist on getting your supplements from a company with a very rigorous quality control program and a policy of rejecting any raw materials that contain contaminants of any kind.

The Bottom Line

1)     The latest study shows that pesticide residues are four-fold lower in the organically raised produce than the conventionally raised produce. This result has been consistently seen in all of the previously published studies, and is probably the #1 reason that people choose organic fruits and vegetables.

2)    Polyphenol antioxidant levels were significantly higher in the organically raised produce. The percent increase ranged from 19% to 69% depending on the polyphenolic compound tested. This increase has not been seen in all previously published studies, but would represent a side benefit if true.

3)    While one of the benefits of organic foods is they are less likely to be contaminated than conventionally grown foods, an organic certification is not a sufficient proof of purity when you are choosing supplements.You should insist on getting your supplements from a company with a very rigorous quality control program and a policy of rejecting any raw materials that contain contaminants of any kind.

 

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.

VTE

Benefits of Omega-3

Author: Dr. Stephen Chaney

venous-thomboembolism

 When a blood clot ends up in your lungs, it can be deadly. But that blood clot didn’t start out in your lungs. It initially formed in your veins where it is referred to as a thrombus. Then it broke off and migrated to your lungs – a process called venous thromboembolism or VTE. Venous thromboembolism is the third most common form of cardiovascular disease, killing around 100,000 Americans each year.

What if something as simple as adding more omega-3 fatty acids to your diet could dramatically decrease your risk of VTE? That’s exactly what a recent study (Hansen-Krone et al, J. Nutr., 144: 861-867, 2014) has suggested. It claims that one of the benefits of omega-3 in your diet may be to help prevent venous thromboembolism.

What Is Venous Thromboembolism or VTE?

As described above, venous thromboembolism starts when a blood clot (also called a thrombis) forms in a vein. About 2/3 of the time, the blood clot forms in the deep veins in the leg (called deep vein thrombosis or DVT) and stays there before eventually dissolving. The symptoms of deep vein thrombosis or DVT are generally leg pain and swelling.

About 1/3 of the time, the clot breaks loose and travels to the lung where it blocks blood flow to a portion of the lung (a process called pulmonary embolism). The symptoms of pulmonary embolism are severe shortness of breath, chest pain when breathing or coughing, and death! While the first two symptoms are pretty frightening, it’s the last symptom (death) that we’d really like to avoid.

Why Might Omega-3s Prevent Venous Thromboembolism or VTE?

One of the benefits of Omega-3s is they have been shown to reduce inflammation and platelet aggregation, two of the most important risk factors for venous thromboembolism. So it is logical to think that omega-3s might help reduce the risk. However, good scientists don’t rely on logic alone. They test their hypotheses by doing clinical studies.

Unfortunately, the results of previous clinical studies have been mixed. One study showed a protective effect of omega-3s, but two other studies found no correlation between omega-3 fatty acid intake and VTE. However, these studies had some significant limitations:

benefits-of-fish-oil-pills

  • They were all performed with populations in the United States where fish consumption is relatively low and many of the fish have low omega-3 content. As a consequence omega-3 fatty acid intake was low and there wasn’t much of a range in intake.
  • Some of the studies did not ask about the use of omega-3 supplements. In a country where 37% of the population takes fish oil supplements, that is a huge omission.
  • They did not measure omega-3 fatty acid levels in the blood to verify that their dietary surveys were accurate.

 

Do Omega-3s Prevent Venous Blood Clots or DVT?

pulmonary-embolism

The current study (Hansen-Krone et al, J. Nutr., 144: 861-867, 2014) followed 23,631 people aged 25-97 from Tromso, Norway for 16 years.

  • The participants filled out a comprehensive dietary survey at the time of enrollment where they indicated the number of times per week they ate fish and how often they used fish oil supplements.
  • The scientists in charge of the study verified the estimated omega-3 intake from the dietary analysis in a subgroup of the population by measuring omega-3 fatty acid levels in their blood.
  • Finally, they utilized Norway’s excellent health records to determine how many of the people in their trial experienced a venous thromboembolism – either fatal or non-fatal.

The results were pretty impressive:

  • Blood level measurements of omega-3 fatty acids verified the omega-3 intake estimates from the dietary survey. There was a direct correlation between estimated intake and blood levels of the omega-3 fatty acids.
  • Those participants who ate fish most often (≥3 times/week) were 22% less likely to experience a VTE than those who ate fish least often (1-2 times/week). That difference was borderline significant.
  • Those participants who ate fish most often and took fish oil supplements were 48% less likely to experience a venous thromboembolism than those who ate fish least often and took no fish oil supplements. That difference was highly significant.

 

Strengths & Weaknesses of the Study

Since not all of the previous clinical studies have reached the same conclusion, it is important to look at the strengths and weaknesses of the study compared to the previous studies.

Strengths of the Study:

  • Tromso is located on the northeast coast of Norway, so fish consumption is high and most of the local fish are excellent sources of omega-3 fatty acids. Consequently, omega-3 intake was relatively high, which significantly increases the chance of seeing an effect if one exists. Fish consumption in the US is generally lower and not all of the fish consumed are good sources of omega-3s.
  • The study also took into account the use of omega-3 supplements. Some of the US studies did not.
  • The estimates of omega-3 intake from the dietary survey were verified by blood analysis of omega-3 fatty acids.

Weaknesses of the Study:

  • The amount of omega-3 fatty acids in the supplements was not recorded, so it is unclear what level of omega-3 fatty acid intake was required to see a significant decrease in VTE risk. This will make it difficult for future investigators to repeat the study.
  • They did not measure other nutrients that might affect the venous thromboembolism risk.

 

The Bottom Line

1)     VTE is a serious condition with a high rate of mortality.

2)     A recent study suggests that a combination of high fish consumption and fish oil supplement use may significantly decrease the risk of venous thromboembolism.

3)     It is interesting to note that even three servings/week of omega-3 rich fish was not enough to cause a significant decrease in venous thromboembolism risk. It required additional omega-3s from fish oil supplements before the decreased risk was significant.

4)     Not all previous studies have come to the same conclusion. So while the most recent study had several improvements in design compared to previous studies, the case can’t be considered closed. More studies are clearly needed.

5)     This study suggests that omega-3 fatty acids may help prevent VTE from occurring. You should not consider them to be a treatment for the condition. If you are experiencing symptoms of venous thromboembolism (leg pain and swelling for deep vein thrombosis (DVT) or shortness of breath and pain when breathing for pulmonary embolism), don’t reach for your fish oil capsules. Call your doctor right away.

 

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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