Do B Vitamins Slow Cognitive Decline?

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

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://healthtipsfromtheprofessor.com/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://healthtipsfromtheprofessor.com/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.

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Comments (5)

  • Gloria Kelley Gonzalez

    |

    Some great information here.

    Reply

  • crissy handley

    |

    I am one who has absorbtion problems of B complex B12 and COQ10. Recently high homocysteine.. With supplementation of Shaklee Bcomplex (4-6 additional plus Vitalizer) and B12, my cognituve function has increased and depression totally in control. This totally makes
    so much sense!! Thank you!

    Reply

    • Dr. Steve Chaney

      |

      Dear Crissy,

      You are a perfect example of the point that I made in my blog post. It is the people who have a B vitamin deficiency (often caused by things like poor absorption) who are most likely to benefit from B vitamin supplementation.

      Dr. Chaney

      Reply

  • Rose Marie Strauss, R.N.

    |

    I have absorption problems.With one tablet of B6/B12 (Trader Joe,s ) suggested use, I take one tablet under the tongue(sublinquel) as a dietary supplement. I need to have my homo-cysteine checked again.I recently had a lab test.and I did not think to ask them to ad this to my lab test.
    It makes a lot sense.Everybody should be informed of
    this great .articles.

    Reply

    • Dr. Steve Chaney

      |

      Dear Rose Marie,

      Sub-lingual Bs are usually not necessary, but it is a good idea to monitor your homocysteine levels. We don’t know whether homocysteine causes cognitive decline, but it does correlate with cognitive decline.

      Dr. Chaney

      Reply

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Latest Article

Should We Use Supplements For Cardiovascular Health?

Posted July 10, 2018 by Dr. Steve Chaney

Are You Just Wasting Your Money On Supplements?

Author: Dr. Stephen Chaney

 

supplements for cardiovascular health wast moneyYou’ve seen the headlines. “Recent Study Finds Vitamin and Mineral Supplements Don’t Lower Heart Disease Risk.”  You are being told that supplements are of no benefit to you. They are a waste of money. You should follow a healthy diet instead. Is all of this true?

If I were like most bloggers, I would give you a simple yes or no answer that would be only partially correct. Instead, I am going to put the study behind these headlines into perspective. I am going to give you a deeper understanding of supplementation, so you can make better choices for your health.

 Should we use supplements for cardiovascular health?

In today’s article I will give you a brief overview of the subject. Here are the topics I will cover today:

  • Is this fake news?
  • Did the study ask the right questions?
  • Is this a question of “Garbage In – Garbage Out?
  • Reducing Heart Disease Risk. What you need to know.

All these topics are covered in much more detail (with references) in my book “Slaying The Supplement Myths”, which will be published this fall.

 

How Was This Study Done?

supplements for cardiovascular healthThis study (D.J.A. Jenkins et al, Journal of the American College Of Cardiology, 71: 2540-2584, 2018 ) was a meta-analysis. Simply put, that means the authors combined the results of many previous studies into a single database to increase the statistical power of their conclusions. This study included 127 randomized control trials published between 2012 and December 2017. These were all studies that included supplementation and looked at cardiovascular end points, cancer end points or overall mortality.

Before looking at the results, it is instructive to look at the strengths and weaknesses of the study. Rather than giving you my interpretation, let me summarize what the authors said about strengths and weaknesses of their own study.

The strengths are obvious. Randomized control trials are considered the gold standard of evidence-based medicine, but they have their weaknesses. Here is what the authors said about the limitations of their study:

  • “Randomized control trials are of shorter duration, whereas longer duration studies might be required to fully capture chronic disease risk.”
  • “Dose-response data were not usually available [from the randomized control studies included in their analysis]. However, larger studies would allow the effect of dose to be assessed.”

There are some other limitations of this study, which I will point out below.

Is This Fake News?

supplements for cardiovascular health fake newsWhen I talk about “fake news” I am referring to the headlines, not to the study behind the headlines. The headlines were definitive: “Vitamin and Mineral Supplements Don’t Lower Heart Disease Risk.” However, when you read the study the reality is quite different:

  • In contrast to the negative headlines, the study reported:
    • Folic acid supplementation decreased stroke risk by 20% and overall heart disease risk by 17%.
    • B complex supplements containing folic acid, B6, and B12 decreased stroke risk by 10%.
    • That’s a big deal, but somehow the headlines forgot to mention it.
  • The supplements that had no significant effect on heart disease risk (multivitamins, vitamin D, calcium, and vitamin C) were ones that would not be expected to lower heart disease risk. There was little evidence from previous studies of decreased risk. Furthermore, there is no plausible mechanism for supposing they might decrease heart disease risk.
  • The study did not include vitamin E or omega-3 supplements, which are the ones most likely to prove effective in decreasing heart disease risk when the studies are done properly (see below).

Did The Study Ask The Right Question?

Most of the studies included in this meta-analysis were asking whether a supplement decreased heart disease risk or mortality for everyone. Simply put, the studies started with a group of generally healthy Americans and asked whether supplementation had a significant effect on disease risk for everyone in that population.

That is the wrong question. We should not expect supplementation to benefit everyone equally. Instead, we should be asking who is most likely to benefit from supplementation and design our clinical studies to test whether those people benefit from supplementation.

supplements for cardiovascular health diagramI have created the graphic on the right as a guide to help answer the question of “Who is most likely to benefit from supplementation?”. Let me summarize each of the points using folic acid as the example.

 

Poor Diet: It only makes sense that those people who are deficient in folate from foods are the most likely to benefit from folic acid supplementation. Think about it for a minute. Would you really expect people who are already getting plenty of folate from their diet to obtain additional benefits from folic acid supplementation?

The NIH estimates that around 20% of US women of childbearing age are deficient in folic acid. For other segments of our population, dietary folate insufficiency ranges from 5-10%. Yet, most studies of folic acid supplementation lump everyone together – even though 80-95% of the US population is already getting enough folate through foods, food fortification, and supplementation. It is no wonder most studies fail to find a beneficial effect of folic acid supplementation.

The authors of the meta-analysis I discussed above said that the beneficial effects of folic acid they saw might have been influenced by a very large Chinese study, because a much higher percentage of Chinese are deficient in folic acid. They went on to say that the Chinese study needed to be repeated in this country.

In fact, the US study has already been done. A large study called “The Heart Outcomes Prevention Evaluation (HOPE)” study reported that folic acid supplementation did not reduce heart disease risk in the whole population. However, when the study focused on the subgroup of subjects who were folate-deficient at the beginning of the study, folic acid supplementation significantly decreased their risk of heart attack and cardiovascular death.  This would seem to suggest using supplements for cardiovascular health is a good idea.

Increased Need: There are many factors that increase the need for certain nutrients. However, for the sake of simplicity, let’s only focus on medications. Medications that interfere with folic acid metabolism include anticonvulsants, metformin (used to treat diabetes), methotrexate and sulfasalazine (used to treat severe inflammation), birth control pills, and some diuretics. Use of these medications is not a concern when the diet is adequate. However, when you combine medication use with a folate-deficient diet, health risks are increased and supplementation with folic acid is more likely to be beneficial.

Genetic Predisposition: The best known genetic defect affecting folic acid metabolism is MTHFR. MTHFR deficiency does not mean you have a specific need for methylfolate. However, it does increase your need for folic acid. Again, this is not a concern when the diet is adequate. However, when you combine MTHFR deficiency with a folate-deficient diet, health risks are increased and supplementation with folic acid is more likely to be beneficial. I cover this topic in great detail in my upcoming book, “Slaying The Supplement Myths”. In the meantime, you might wish to view my video, “The Truth About Methyl Folate.”

Diseases: An underlying disease or predisposition to disease often increases the need for one or more nutrients that help reduce disease risk. The best examples of this are two major studies on the effect of vitamin E on heart disease risk in women. Both studies found no effect of vitamin E on heart disease risk in the whole population. However, one study reported that vitamin E reduced heart disease risk in the subgroup of women who were post-menopausal (when the risk of heart disease skyrockets). The other study found that vitamin E reduced heart attack risk in the subgroup of women who had pre-existing heart disease at the beginning of the study.

Finally, if you look at the diagram closely, you will notice a red circle in the middle. When two or three of these factors overlap, that is the “sweet spot” where supplementation is almost certain to make a difference and it may be a good idea to use supplements for cardiovascular health.

Is This A Question Of “Garbage In, Garbage Out”?

supplements for cardiovascular health garbage in outUnfortunately, most clinical studies focus on the “Does everyone benefit from supplementation question?” rather than the “Who benefits from supplementation?” question.

In addition, most clinical studies of supplementation are based on the drug model. They are studying supplementation with a single vitamin or mineral, as if it were a drug. That’s unfortunate, because vitamins and minerals work together synergistically. What we need are more studies of holistic supplementation approaches.

Until these two things change, most supplement studies are doomed to failure. They are doomed to give negative results. In addition, meta-analyses based on these faulty supplement studies will fall victim to what computer programmers refer to as “Garbage In, Garbage Out”. If the data going into the analysis is faulty, the data coming out of the study will be equally faulty. It won’t be worth the paper it is written on. If you are looking for personal guidance on supplementation, this study falls into that category.

 

Should We Use Supplements For Cardiovascular Health?

 

If you want to know whether supplements decrease heart disease risk for everyone, this meta-analysis is clear. Folic acid may decrease the risk of stroke and heart disease. A B complex supplement may decrease the risk of stroke. All the other supplements they included in their analysis did not decrease heart disease risk, but the analysis did not include vitamin E and/or omega-3s.

However, if you want to know whether supplements decrease heart disease risk for you, this study provides no guidance. It did not ask the right questions.

I would be remiss, however, if I failed to point out that we know healthy diets can decrease heart disease risk. In the words of the authors: “The recent science-based report of the U.S. Dietary Guidelines Advisory Committee, also concerned with [heart disease] risk reduction, recommended 3 dietary patterns: 1) a healthy American diet low in saturated fat, trans fat, and meat, but high in fruits and vegetables; 2) a Mediterranean diet; and 3) a vegetarian diet. These diets, with their accompanying recommendations, continue the move towards more plant-based diets…” I cover the effect of diet on heart disease risk in detail in my book, “Slaying The Food Myths”.

 

The Bottom Line

 

You have probably seen the recent headlines proclaiming: “Vitamin and Mineral Supplements Don’t Lower Heart Disease Risk.” The study behind the headlines was a meta-analysis of 127 randomized control trials looking at the effect of supplementation on heart disease risk and mortality.

  • The headlines qualify as “fake news” because:
    • The study found that folic acid decreased stroke and heart disease risk, and B vitamins decreased stroke risk. Somehow the headlines forgot to mention that.
    • The study found that multivitamins, vitamin D, calcium, and vitamin C had no effect on heart disease risk. These are nutrients that were unlikely to decrease heart disease risk to begin with.
    • The study did not include vitamin E and omega-3s. These are nutrients that are likely to decrease heart disease risk when the studies are done properly.
  • The authors of the study stated that a major weakness of their study was that that randomized control studies included in their analysis were short term, whereas longer duration studies might be required to fully capture chronic disease risk.
  • The study behind the headlines is of little use for you as an individual because it asked the wrong question.
  • Most clinical studies focus on the “Does everyone benefit from supplementation question?” That is the wrong question. Instead we need more clinical studies focused on the “Who benefits from supplementation?” question. I discuss that question in more detail in the article above.
  • In addition, most clinical studies of supplementation are based on the drug model. They are studying supplementation with a single vitamin or mineral, as if it were a drug. That’s unfortunate, because vitamins and minerals work together synergistically. What we need are more studies of holistic supplementation approaches.
  • Until these two things change, most supplement studies are doomed to failure. They are doomed to give negative results. In addition, meta-analyses based on these faulty supplement studies will fall victim to what computer programmers refer to as “Garbage In, Garbage Out”. If the data going into the analysis is faulty, the data coming out of the study will be equally faulty. It won’t be worth the paper it is written on. If you are looking for personal guidance on supplementation, this study falls into that category.
  • If you want to know whether supplements decrease heart disease risk for everyone, this study is clear. Folic acid may decrease the risk of stroke and heart disease. A B-complex supplement may decrease the risk of stroke. All the other supplements they included in their analysis did not decrease heart disease risk, but they did not include vitamin E and/or omega-3s in their analysis.
  • If you want to know whether supplements decrease heart disease risk for you, this study provides no guidance. It did not ask the right questions.
  • However, we do know that healthy, plant-based diets can decrease heart disease risk. I cover heart healthy diets in detail in my book, “Slaying The Food Myths.”

 

For more details, read the article above.

 

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

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