Does Vitamin D Prevent Depression?

Why You Can’t Believe Everything You Read

depressionThe days are getting shorter and Seasonal Depression, often called the “winter blues”, will soon be upon us. Most of the research on Seasonal Depression has centered on the effect of sunlight on our hormones.

However, sunlight is also responsible for the synthesis of vitamin D in our skin cells. So, some experts have hypothesized that low levels of 25-hydroxyvitamin D, the active form of vitamin D, in our blood also play a role in the winter blues.

If so, that could have important implications for managing depression, especially in older adults. Depression is estimated to affect around 6.5 million of the 49 million adults over the age of 65 in our country. Treatment costs for older adults in this country are estimated at $9 billion/year.

If something as simple and inexpensive as a vitamin D supplement could reduce the risk of depression, it would be a huge boon to our health care system.

Association studies suggest that may be a possibility. For example, one recent meta-analysis of 6 clinical studies (H Li et al, The American Journal of Geriatric Psychiatry, 27: P1192-1202, 2019) reported that every 10 ng/mL increase in 25-hydroxyvitamin D was associated with a 12% decrease in the risk of depression in older adults.

However, association studies do not prove cause and effect.

Unfortunately, randomized, placebo controlled clinical trials have given mixed results. A few studies suggested that vitamin D might reduce depression risk, but most of the studies found no effect of vitamin D on depression risk. However, most of the published studies have been poorly designed They were too small, too short, or did not use validated methods for measuring depression.

This was the genesis of the current study (OI Okerke et al., JAMA, 324: 471-480, 2020). It was designed to be a definitive study that would avoid the defects of previous studies.

The study concluded that vitamin D supplementation does not decrease the risk of depression in older adults, and those were the headlines you have probably seen. But is that conclusion true? Let’s take a peek behind the curtain and analyze the study.

How Was The Study Done?

Clinical StudyThis study was an offshoot of the VITAL (VITamin D and OmegaA-3 TriaL) clinical study, so let me start by describing the characteristics of that study.

The VITAL study (JE Manson et al, New England Journal of Medicine, DOI: 10.1056/NEJMoa1811403) enrolled 25,871 healthy adults (average age = 67) in the United States. The study participants were 50% female, 50% male, and 20% African American. None of the participants had preexisting cancer or heart disease.

Study participants were given questionnaires on enrollment to assess clinical and lifestyle factors including dietary intake. Blood samples were taken from about 65% of the participants to determine 25-hydroxyvitamin D levels (a measure of vitamin D status) at baseline and at the end of the first year to assess the effectiveness of vitamin D supplementation. The participants were given either 2,000 IU of vitamin D/day or a placebo and followed for an average of 5.3 years.

This study consisted of 18,353 participants from the VITAL study. Ninety percent of the participants had no previous history of depression. Ten percent had previously been diagnosed or treated for depression but had been depression-free for over 2 years.

The participants filled out annual questionnaires to quantify the onset of depression by three criteria:

  • A diagnosis of depression by a physician.
  • Treatment for depression (medications, counseling, or both).
  • A questionnaire designed to evaluate symptoms of depression. The authors of the study referred to this as an assessment of their mood.

During the 5.3 year follow up period 3.6% of the participants reported the onset of diagnosed depression or a mood consistent with depression. This is consistent with previous studies showing that 1-5% of healthy, non-institutionalized older adults suffer from depression.

Does Vitamin D Prevent Depression?

thumbs down symbolThe results of the study were clear.

Treatment with 2,000 IU of vitamin D3 compared to placebo for 5.3 years did not have a statistically significant effect on:

  • The incidence or recurrence of depression diagnosis, or…
  • Treatment for depression, or…
  • Clinically relevant depressive symptoms.

The authors concluded, “These findings do not support the use of vitamin D3 in adults to prevent depression.”

Why You Can’t Believe Everything You Read

It would be tempting to say, “Case closed. We now know for certain that vitamin D has no effect on depression.”

After all, this was an excellent study. It was large (18,353 participants), lasted a long time (5.3 years), and used well established measures of depression. What’s not to like?

Peek Behind The CurtainUnfortunately, even well-designed studies can give misleading results. Let’s take a peek behind the curtain and see where this study went astray.

There were two glaring deficiencies in this study.

#1: Most of the participants had adequate vitamin D status at the beginning of the study. The average 25-hydroxyvitamin D level of participants at the beginning of the study was 31 ng/mL (78 nmol/L). The NIH considers 20-50 ng/mL (50-125 nmol/L) to be an adequate level of 25-hydroxyvitamin D for most physiological functions. This means that study participants started in the middle of the adequate range with respect to vitamin D status.

This was not a failure of study design. In fact, the authors of the study are to be commended for measuring the vitamin D status of participants at the beginning of the study. Many previous studies have neglected to do that.

The problem is that vitamin D has become extremely popular. Many Americans are already taking multivitamins or vitamin D supplements. To recruit enough people for the study the authors were forced to allow participants to enter the study even if they were taking vitamin D supplements, as long as the amount did not exceed 800 IU/day.

In short, most of the participants in this study were already supplementing with up to 800 IU/day of vitamin D. If so, they were allowed to continue taking their vitamin D supplements. The 2,000 IU of vitamin D was added to what they were already taking.

The question then becomes, if people are already taking RDA levels of supplemental vitamin D and their blood levels of 25-hydroxyvitamin D are already in the adequate range, do we really expect additional supplemental vitamin D to have a beneficial effect?

The author’s answer to that question was, “The mean baseline 25-hydroxyvitamin D level was 30.8 ng/mL; this value is already at a threshold for extraskeletal health benefits [health benefits other than bone health], and so the ability to observe effects of vitamin D3 supplementation may have been attenuated. [To determine whether vitamin D supplementation reduces the risk of depression] large-scale studies would be required to address the effects of high-dose, long-term vitamin D3 supplementation among those with nutrient deficiency.”

My more direct answer would be, “This study provides no useful information on whether vitamin D3 supplementation reduces the risk of depression. What is needed are studies that start with a population that is deficient in vitamin D.”

An accurate conclusion from this study would have been, “If you are already taking vitamin D supplements and/or have an adequate vitamin D status, supplementation with an extra 2,000 IU of vitamin D3 provides no additional benefit with respect to the risk of developing depression.” But that is not what the headlines said.

#2: The study did not record the reason for the onset of depression. That is important because the top 3 causes of depression in adults 65 and older are:

  • Loss of a spouse or partner.
  • Chronic health issues.
  • Restricted blood flow to the brain.

It is unlikely that vitamin D supplementation would have much of an effect on these issues.

In contrast, seasonal depression, which is more likely to be affected by vitamin D supplementation, was not measured in this study.

The Bottom Line

You may have seen recent headlines saying that vitamin D supplementation has no effect on the risk of developing depression.

The study behind these headlines was a very well-designed study. It was large (18,353 participants), lasted a long time (5.3 years), and used well established measures of depression.

It would be tempting to say, “Case closed. We now know for certain that vitamin D supplementation has no effect on depression.”

Unfortunately, even well-designed studies can give misleading results. This one had a major flaw that made the data almost useless.

The problem is that most Americans are already taking multivitamins or vitamin D supplements. To recruit enough people for the study the authors were forced to allow participants to enter the study even if they were taking vitamin D supplements, as long as the amount did not exceed 800 IU/day.

That meant that most participants already had adequate blood levels of 25-hydroxyvitamin D at the beginning of the study.

The question then becomes, if people are already taking RDA levels of supplemental vitamin D and their blood levels of 25-hydroxyvitamin D are already in the adequate range, do we really expect additional supplemental vitamin D to have a beneficial effect? The answer is, “Probably not”.

Rather than saying that this study definitively shows that vitamin D supplementation has no effect on the risk of developing depression, I feel it would be more accurate to say, “This study provides no useful information on whether vitamin D3 supplementation reduces the risk of depression. What is needed are studies that start with a population that is deficient in vitamin D.”

An accurate conclusion from this study would have been, “If you are already taking vitamin D supplements and/or have an adequate vitamin D status, supplementation with an extra 2,000 IU of vitamin D3 provides no additional benefit with respect to the risk of developing depression.” But that is not what the headlines said.

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.

What Supplements Help Mental Health?

Do Omega-3s Reduce Depression?

Author: Dr. Stephen Chaney

depressionWe are in the midst of a mental health crisis. According to the latest statistics:

·       19% of adults in the United States have some form of mental illness.

·       16.5% of youth ages 6-17 have some form of mental illness.

·       The 5 most commonly diagnosed forms of mental illness are anxiety, depression, post-traumatic stress disorder, bipolar disease, and ADHD.

Even worse, mental illness appears to be increasing at an alarming rate among young people. For example:

·       Between 2005 and 2017 depression increased 52% among adolescents.

·       Between 2002 and 2017 depression increased 63% in young adults.

·       Between 1999 and 2014 suicides have increased 24% in young adults. In the past few years suicides have been increasing by 2% a year in this group.

Much has been written about the cause of this alarming increase in mental illness. The short answer is that we don’t really know. But the most pressing question is what do we do about it?

The medical profession relies on powerful drugs to treat the symptoms of mental illness. These drugs don’t cure drug side effectsthe illness. They simply keep the symptoms under control. Plus, if you have ever listened closely to the advertisements for these drugs on TV, you realize that they all have serious side effects that adversely affect your quality of life.

My “favorite” example is drugs for anxiety and depression. You are told that one of the side effects is “suicidal thoughts”. That means that the very drug someone could be prescribed to prevent suicides might actually increase their risk of suicide. Why would anyone take such a drug?

If drugs are so dangerous, what about supplements? Do they provide a safe, natural alternative for reducing the symptoms of mental illness? Some supplement companies claim their products cure mental illness. Are their claims true or are they just trying to empty your wallet?

How is a consumer to know which of these supplement claims are true and which are bogus? Fortunately, an international team of scientists has scoured the literature to find out which supplements have been proven to reduce mental health symptoms.

How Was The Study Done?

clinical-studyThis was a massive study (J. Firth et al, World Psychiatry, 18: 308-324, 2019.  It was a meta-review of 33 meta-analyses of randomized, placebo-controlled trials with a total of 10,951 subjects. The clinical trials included in this analysis analyzed the effect of 12 nutrients, either alone or in combination with standard drug treatment, on symptoms associated with 10 common mental disorders.

To help you understand the power of this meta-review, let me start by defining the term “meta-analysis”. A meta-analysis combines the data from multiple clinical studies to increase the statistical power of the data. Meta-analyses are considered to be the gold standard of evidence-based evidence.

However, not all meta-analyses are equally strong. They suffer from the “Garbage-In, Garbage-Out” phenomenon. Simply put, they are only as strong as the weakest clinical studies included in their analysis.

That is the strength of this meta-review. It did not simply combine the data from all 33 meta-analyses. It used stringent criteria to evaluate the quality of each meta-analysis and weighted the data appropriately.

What Supplements Help Mental Health?

omega-3 fish oil supplementThe strongest evidence was for omega-3 supplements. In the worlds of the authors:

·       “Across 13 independent randomized control clinical trials in 1,233 people with major depression, omega-3 supplements reduced depressive symptoms significantly.”

o   The average dose of omega-3s in these studies was 1,422 mg/day of EPA.

o   The effect was strongest for omega-3 supplements containing more EPA than DHA and for studies lasting longer than 12 weeks.

o   There was no evidence of publication bias in these studies. This is a very important consideration. Publication bias means that only studies with a positive effect were published while studies showing no effect were withheld from publication. That makes the effect look much more positive than it really is. The fact there was no evidence of publication bias strengthens this conclusion.

o   Omega-3 supplements were more effective when used in combination with antidepressant drugs, but there was some evidence of publication bias in those studies.

·       “Across 16 randomized control clinical trials reporting on ADHD symptom domains, significant benefits were observed for both hyperactivity/impulsivity and inattention.”

·       Omega-3s had no significant effect on schizophrenia or bipolar disorder other than a mild reduction in depressive symptoms.

There was strong, but not definitive, evidence for folic acid and methylfolate supplements for depression.

·       When used in conjunction with antidepressants both folic acid and methylfolate supplements “…were associated with significantly greater reductions in depressive symptoms compared to placebo, although there was large heterogeneity between trials.”

·       The largest effects were observed with high dose methylfolate. In the words of the authors: “Two randomized control clinical trials examining a high dose (15 mg/day) of methylfolate administered in combination with antidepressants found moderate-to-large benefits for depressive symptoms.” However, to put this into perspective:

o   15 mg/day is 3,750% of the RDA. This is a pharmacological dose and should only be administered under the care of a physician.

o   A smaller dose of 7.5 mg/day is ineffective.

o   No comparison was made with folic acid at this dose, so we do not know whether folic acid would be equally effective.

·       The authors concluded that there is emerging evidence for positive effects of vitamin D (>1,500 vitamin d supplementationIU/day) for major depressive disorders and N-acetylcysteine (2-3 gm/day) in combination with drugs for mood disorders and schizophrenia. The term “emerging evidence” means there have been several recent studies reporting positive results, but more research is needed.

·       The authors did not find evidence supporting the use of other vitamin and mineral supplements (E, C, zinc, magnesium, and inositol) for treating mental health disorders.

·       The authors did not find enough high-quality studies to support claims about the effects of prebiotics or probiotics on mental health disorders.

Do Omega-3s Reduce Depression?

Happy WomanThe evidence supporting the effectiveness of omega-3s in reducing symptoms of depression is strong. In the words of the authors: “The nutritional intervention with the strongest evidentiary support is omega-3, in particular EPA. Multiple meta-analyses have demonstrated that it has significant effects in people with depression, including high-quality meta-analyses with good confidence in findings…”

However, before you throw away your antidepressants and replace them with an omega-3 supplement, let me put this study into perspective for you.

·       Depression can be a serious disease. If you just feel a little blue from time to time, try increasing your omega-3 intake. However, if you have major depression, don’t make changes to your treatment plan without consulting your physician.

·       The best results were obtained when omega-3s were used in combination with antidepressants. This should be your starting point.

·       Ideally, adding omega-3s to your treatment plan will allow your doctor to reduce or eliminate the drugs you are taking. That would have the benefit of reducing side effects associated with the drugs. However, I would like to re-emphasize this is a decision to take in consultation with your doctor. [My only caveat is if your doctor is unwilling to even consider natural approaches like omega-3 supplementation, it might be time to find a new doctor.]

·       Finally, omega-3 supplementation is only one aspect of a holistic approach to good mental health. A healthy diet, exercise, supplementation, and stress reduction techniques all work together to keep your mind in tip-top shape.

The Bottom Line

There are lots of supplements on the market promising to cure depression and other serious mental health issues. Are they effective or are the claims bogus? Fortunately, a recent meta-review of 33 meta-analyses of high-quality clinical trials has answered that question. Here is their conclusion:

·       The evidence is strongest for omega-3s and depression.

o   The average dose of omega-3s in these studies was 1,422 mg/day of EPA.

o   The effect was strongest for omega-3 supplements containing more EPA than DHA and for studies lasting longer than 12 weeks.

·       There is fairly strong evidence for folate/folic acid supplements and depression, although there was large heterogeneity between trials.

·       There is emerging evidence for vitamin D (>1,500 IU/day) and depression and N-acetylcysteine (2-3 gm/day) for depression and schizophrenia.

·       Evidence for other supplements is currently inconclusive.

However, before you throw away your antidepressants and replace them with an omega-3 supplement, let me put this study into perspective for you.

·       Depression can be a serious disease. If you just feel a little blue from time to time, try increasing your omega-3 intake. However, if you have major depression, don’t make changes to your treatment plan without consulting your physician.

·       The best results were obtained when omega-3s were used in combination with antidepressants. That should be your starting point.

·       Ideally, adding omega-3s to your treatment plan will allow your doctor to reduce or eliminate the drugs you are taking. That would have the benefit of reducing side effects associated with the drugs.

·       Finally, omega-3 supplementation is only one aspect of a holistic approach to good mental health. A healthy diet, exercise, supplementation, and stress reduction techniques all work together to keep your mind in tip-top shape.

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.

 

Is There Really Such A Thing A Positive Stress?

Stress Can Be Your Friend

Author: Dr. Pierre DuBois

Motorbike racing on the track.Do you consider yourself an optimist or a pessimist? When the going gets tough, the optimists among you can take heart—new research that has found that viewing stress positively can be of benefit to both the mind and body.

When the brain perceives stress (either physical or psychological), it reacts by releasing cortisol, adrenaline and norepinephrine to prepare the body for a “fight or flight” response. Fortunately for us, this response is not triggered in most people today as frequently as it once was or for the same kinds of reasons.

After all, relatively few of us are in life-threatening situations on a regular basis. Today’s “modern” stresses are more likely to be caused by wrestling with the IRS, trying to escape a traffic jam or competing with a coworker for a promotion.

It is interesting to note that stress, in itself, is not necessarily a negative thing. It is how we perceive it that makes it either good or bad for us. This is a hopeful discovery, as most people have only limited control over how much stress they experience. The everyday stresses of modern life are difficult to escape. But if we can train our minds to view them as a challenge rather than a threat, it could actually help to bring about better health.

Scientists from a handful of universities, including Yale University and Columbia University, examined the effects of stress on 300 investment bankers who had just emerged from a round of layoffs (I know it’s difficult to feel bad for the stress of investment bankers, but stay with me here). In the study, published in the Journal of Personality and Social Psychology, scientists divided the participants into two groups, and tried to alter the perception of half of them to view stress as debilitating and the other half to view it as an enhancement.

The first half of the participants were shown videos of people succumbing to stress. The other half were shown videos of people meeting challenges, such as sports figures accomplishing a difficult goal. The results showed that those who had a more optimistic view of stress had fewer health problems, including headaches and muscle pain, and performed better at work than the pessimistic group. In addition, levels of cortisol (the stress hormone) were lower in those who viewed stress as potentially enhancing.

There is actually a term for positive stress, called eustress, which was coined by endocrinologist Hans Selye in the 1970s. It has been proven that stress in moderation improves cognitive performance and improves memory.

Good stress involves the kind of challenges where we feel that we are in control and are accomplishing something. It boosts the immune system and can improve heart function. So eliminating all stress from our lives is probably not a good idea.

The stress to watch out for is the chronic, long-term emotional stress, which causes stress hormones to remain at persistently high levels, leading to many chronic ailments such as heart disease, high blood pressure and depression.

However, viewing certain stressors as challenges rather than threats can be a positive thing and can help ensure that you have a healthy, satisfying and exciting life.

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-3 Fatty Acids Decrease Risk Of Depression In Women?

Do Happy Fish Make Happy Women?

Author: Dr. Stephen Chaney

Woman playing with autumn leaves The days are getting shorter, and those shorter days can lead to depression. You may have seen the recent headlines saying “Omega-3 fatty acids may decrease the risk of depression in women”. If you suffer from seasonal depression, should you be stocking up on fish oil capsules? Let’s look at the study behind the headlines.

The Theory Behind The Study

Depression appears to be increasing in modern society. For example, between 1991 and 2002, the prevalence of major depression has more than doubled in the United States from 3.3% to 7.1%.

There are many causes of depression, but some experts blame the dramatic increase in omega-6 fatty acids in the diet.  For example, per capita consumption of soybean oil, much of it in processed foods, has increased 1000-fold during the past century. That’s a concern because omega-6 fatty acids interfere with the body’s ability to convert vegetable sources of omega-3 fatty acids into the longer chain omega-3 fatty acids thought to be effective in reducing depression.

This has lead to the hypothesis that omega-3 fatty acids in the diet may help prevent depression, and a number of clinical studies have supported that hypothesis.

How Was The Study Designed?

The study (M. A. Beydoun et al, J. Nutr., doi: 10.3945/jn.113.179119, 2013) looked at 1,746 adults age 30-64 living in Baltimore Maryland. The participants were a representative sample of African Americans and whites, men and women. Omega-3 fatty acid intake was based on two 24-hour dietary recalls. Depressive symptoms were based on something called CES-D, which is a 20 item, self-reporting symptom rating scale.

What Did The Study Actually Show?

The results were pretty dramatic for women:

  • Women with the highest intake of omega-3 fatty acids/day were 49% less likely to suffer from depression than women with the lowest intake.
  • No significant effect of omega-3 fatty acid intake on the prevalence of depression was seen for the men in this study. This was the first study to look at men and women separately, so it’s not yet clear whether this is a true sex-specific difference or simply due to the relatively small sample size and reduced incidence of depression in men.

Limitations Of The Study:

There were numerous limitations to this study, but the most important were:

  • It did not ask whether the participants were taking fish oil supplements, and it did not substantiate the dietary recalls by measuring actual levels of omega-3 fatty acids in the blood.
  • It just measured associations, not cause and effect.

The Bottom Line:

This is not a particularly strong study, but it is consistent with a least half a dozen other studies that have obtained similar results. So, based on the total body of published studies my recommendations are:

1)     If you are a woman and you’re suffering from mild depression you might want to talk with your doctor about increasing your omega-3 fatty acid intake before you start taking an anti-depressive medication. Omega-3 fatty acids may reduce heart disease risk, lower inflammation and provide other benefits. The drugs generally have side effects rather than side benefits.

2)    We don’t have any good data yet on what dose of omega-3 fatty acids are needed, but the 500-1,000 mg/day that the NIH recommends for heart health might be a good starting place.

3)     If you’re a guy, this paper suggests that the jury is out about whether omega-3s can help you with depression. More studies will be required. In the meantime, just remember that omega-3s have lots of other health benefits.

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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