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Do Omega-3s Slow Cognitive Decline?

September 9, 2014 by Dr. Steve Chaney

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

Author: Dr. Stephen Chaney

Who 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 Mini-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.

The 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?

September 2, 2014 by Dr. Steve Chaney

The B Vitamin Controversy

Author: Dr. Stephen Chaney

Do 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://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:

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 (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?

That 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://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.

Nitric Oxide Benefits and Side Effects

August 19, 2014 by Dr. Steve Chaney

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).

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

There 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.

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.

Risk Factors of Prostate Cancer

July 29, 2014 by Dr. Steve Chaney

Vitamin D Deficiency?

Author: Dr. Stephen Chaney

Is vitamin D deficiency one of the risk factors of prostate cancer? What if something as simple as maintaining optimal vitamin D status could decrease your risk of prostate cancer? There is a lot of indirect evidence suggesting that vitamin D deficiency might affect your risk of developing prostate cancer. For example:

Prostate cancer incidence and vitamin D deficiency parallel each other. Both are highest in northern latitudes, in African American men, and in older men.
Prostate cancer mortality rates are highest for patients diagnosed in the winter and at Northern latitudes.

However, clinical studies looking at the correlation between 25-hydroxy vitamin D (the biologically active form of vitamin D in the blood) and prostate cancer incidence have been inconsistent. Because of this there has been considerable controversy in the scientific community as to whether or not there was any correlation between vitamin D deficiency and prostate cancer.

Vitamin D Deficiency and Cancer

That’s what makes the recent headlines suggesting that vitamin D is associated with decreased risk of aggressive prostate cancer so interesting. Does this study show low vitamin D to be one of the risk factors of prostate cancer? Have the conflicting data on vitamin D deficiency and prostate cancer finally been resolved or is this just another case of dueling headlines? Let’s start by looking at the study itself.

This study (Murphy et al, Clinical Cancer Research, 20: 2289-2299, 2014) enrolled 667 men, aged 40-79 (average age = 62), from five urology clinics in Chicago over a four year period. These were all men who were undergoing their first prostate biopsy because of elevated serum PSA levels or an abnormal DRE (that’s doctor talk for digital rectal exam – the least favorite part of every guy’s physical exam). The clinics also drew blood and measured each patient’s 25-hydroxy vitamin D level at the time of the prostate biopsy.

This study had a number of important strengths:

It was conducted at a northern latitude. Because of that 41.2% of the men in this study were vitamin D deficient (<20 ng/ml) and 15.7% were severely vitamin D deficient (<12 ng/ml). That’s important because you need a significant percentage of patients with vitamin D deficiency to have any chance of seeing an effect of vitamin D status on prostate cancer risk.

The study had equal numbers of African American and European American men. That’s important because African American men have significantly lower 25-hydroxy vitamin D status and significantly higher risk of prostate cancer than European American men.

All of the men enrolled in the study had elevated PSA levels or abnormal DREs. That’s important because it meant that all of the men enrolled in the study were at high risk of having prostate cancer. That made the correlation between vitamin D status and prostate cancer easier to detect.

This was the first study to correlate 25-hydroxyvitamin D levels with prostate biopsies at the time of biopsy. That’s important because it allowed the investigators to distinguish between aggressive tumors (which require immediate treatment and have a higher probability of mortality) and slow growing tumors (which may simply need to be monitored).

The results were pretty dramatic:

In African American men vitamin D deficiency (<20 ng/ml) was associated with an increased risk of prostate cancer diagnosis at time of biopsy.

In both European American and African American men severe vitamin D deficiency (<12 ng/ml) was associated with increased risk of aggressive prostate cancer diagnosis at time of biopsy.

The authors concluded: “Our work supports the hypothesis that 25-hydroxy vitamin D is a potential biomarker that plays a clinically significant role in prostate cancer, and it may be a useful modifiable risk factor in the disease”.

That’s “science speak” for “adequate vitamin D status may help prevent prostate cancer” or “low vitamin D may indeed be one of the risk factors of prostate cancer.”

Why Have Some Studies Failed To Find A Correlation Between Vitamin D Deficiency and Prostate Cancer?

The authors of the current study had an interesting hypothesis for why some previous studies have not seen an association between vitamin D status and prostate cancer risk. When you compare all of the previous studies, the strongest correlations between vitamin D deficiency and prostate cancer were the studies conducted at northern latitudes, in African American men, or focusing on aggressive prostate cancer as an end point.

That offers a few clues as to why other studies may have failed to find a link between vitamin D status and prostate cancer risk. For example:

The clue that the correlation between vitamin D deficiency and prostate cancer risk was strongest at northern latitudes and with African American men suggests that you need to have a significant percentage of subjects with deficient or very deficient levels of 25-hydroxy vitamin D before you can see a correlation. Other studies may have failed to show a correlation simply because most of the men in the study had normal vitamin D status.

The clue that the correlation is strongest for aggressive prostate cancer is more subtle. The authors hypothesized that prostate cancer develops over a lifetime. If that is the case, measuring vitamin D deficiency at the time of diagnosis may not represent the lifetime vitamin D status. The vitamin D status could have decreased because the men were older or had become overweight, or the vitamin D status could have changed simply because they moved from one geographical location to another.

In contrast, the progression from benign to aggressive prostate cancer is generally short term, so it would be affected by the most recent vitamin D status. If that is the case, then the vitamin D status measured at the time of diagnosis may more accurately reflect the vitamin D deficiency that affected the aggressiveness of the cancer.

The Bottom Line

1) The latest study suggests that vitamin D deficiency (<20 ng/ml serum 25-hydroxy vitamin D) may significantly increase the risk of prostate cancer. The correlation between low vitamin D status and prostate cancer risk is strongest for African American men.

2) The study also suggests that severe vitamin D deficiency (<12 ng/ml serum 25-hydroxyvitamin D) may significantly increase the risk of aggressive prostate cancer in both African American and European American men.

3) This is a very well done study, and it is consistent with many, but not all, of the previous studies. Clearly more research needs to be done. Future research should be focused on high risk subjects and subjects with low vitamin D status so that the correlation between vitamin D status and prostate cancer risk can be adequately tested.

4) This is another example of why I recommend that you have your serum 25-hydroxy vitamin D level measured on a regular basis and that you aim to keep it in the normal range (20-80 ng/ml). Some experts believe that 30-80 ng/ml is optimal.

5) If you are African American, overweight, live in northern latitudes or it is winter, you may need supplemental vitamin D3. 1,000 – 4,000 IU/day of vitamin D3 is generally considered to be safe. If higher amounts are needed to normalize your 25-hydroxy vitamin D levels I recommend that you consult your physician for the appropriate dose.

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 Calcium Supplements Increase Heart Attack Risk?

July 15, 2014 by Dr. Steve Chaney

Calcium Confusion

Author: Dr. Stephen Chaney

Should you avoid calcium supplements? Do calcium supplements increase heart disease risk? If you’ve been reading some of the recent headlines in magazines, newspapers and current health articles, that’s exactly what you might think.

And, after years of telling us that calcium supplements may be important for bone health, even some doctors are now recommending that their patients avoid calcium supplements. So what’s the truth? What should you believe?