B vitamins Archives - Health Tips From The Professor

Which Nutrients Prevent Prenatal Depression?

May 14, 2024 by Dr. Steve Chaney

What Does This Study Mean For You?

Author: Dr. Stephen Chaney

Yes, you read the headline correctly. Everyone talks about postnatal depression. But prenatal depression is also a “thing”, especially during the third trimester.

Worldwide, 4-20% of women experience some degree of depression during the third trimester – with pregnant women in high-income countries at the lower end (4-10%) of depression risk.
In contrast, the incidence of postnatal depression is 10-15%.

It is probably no coincidence that the incidence of depression is greatest during the third trimester and during the postnatal period.

The third trimester is the most difficult part of pregnancy for many women.
When a woman brings her baby home from the hospital her orderly life becomes chaotic.

But what role does nutrition play?

While not definitive, many studies suggest that supplementation with B vitamins, especially folic acid, B6, and B12; omega-3 fatty acids; vitamin D; and iron reduce the risk of postnatal depression.
However, there is much less information on which nutrients reduce the risk of prenatal depression.

Based on studies suggesting both iron and vitamin D deficiencies may negatively impact mental health, the authors of this study (JL Evanchuk et al, The Journal Of Nutrition. 154, 174-184, 2024) set out to determine whether iron and/or vitamin D deficiencies increase the risk of prenatal depression during the first trimester.

How Was This Study Done?

The authors recruited 2189 newly pregnant mothers from Calgary and Edmonton in Ontario Canada between 2009 and 2012. Participants in the study visited clinics in the area upon entry into the study; midway through the first, second, and third trimesters; and at multiple timepoints up to 3 months during the postpartum period.

In addition to the usual pregnancy wellness tests, participants filled out a 24-hour dietary recall and a Supplemental Intake Questionnaire to determine intakes of iron and vitamin D.

Note: The participants were all advised to take some form of prenatal supplement during the study. That’s because prenatal supplements are considered “the standard of care” for pregnant woman, so it would be considered unethical not to include a prenatal supplement in this study.

At the mid-point of the second trimester blood samples were drawn and analyzed for biomarkers of iron and vitamin D insufficiency. For iron the biomarkers were serum ferritin, soluble transferrin receptor, and hepcidin. For vitamin D, the biomarkers were 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and 3-epi-25-hydroxyvitamin D.

Iron deficiency was defined as serum ferritin levels <15 µg/L. Vitamin D insufficiency was defined as 25-hydroxyvitamin D levels < 75nmol/L. The other biomarkers were used to confirm these diagnoses.

Maternal depression was measured midway through the third trimester and ~3 months postpartum using 10-item questionnaire called the Edinburg Postnatal Depression Scale (EPDS). The EPDS ranks depression on a scale of 0 to 30, with a score of ≥13 considered an indication of likely depression.

The characteristics of the women enrolled in this study were:

Average age = 31.5
Average prepregnancy BMI = 23 (healthy weight).
Married or cohabitating with a partner = 97%.
Highly educated (college or postgraduate degree) = 68%.
Income above $70,000/year = 78%.
First child = 54%.
White = 80%.

Based on the Edinburg Depression Scale, probably depression for the 1822 women who completed the study was 5.6% during the third trimester and 4.4% 3 months postpartum.

Note: The low incidence of depression seen in this study was probably due to:

The women in this study were of high socioeconomic status and were receiving excellent healthcare.

The women in this study were taking prenatal supplements that provided both iron and vitamin D.

Which Nutrients Prevent Prenatal Depression?

As I mentioned when describing how the study was designed, all participants in this study were advised to take a prenatal supplement. Consequently:

94% of the women in this study were taking a supplement containing iron with an average supplemental iron intake of 26 mg/day.

- Note: The RDA for iron during pregnancy is 30 mg/day and most prenatal supplements provide 27 mg/day.

68% of the women in this study were taking a supplement containing vitamin D, with an average supplemental vitamin D intake of 330 IU/day.

- Note: The RDA for vitamin D during pregnancy is 600 IU/day, but most prenatal supplements provide far less than that.

When the investigators looked at iron and vitamin D status during the second trimester:

63.3% of the women had adequate levels of both iron and vitamin D.

14.8% of the women were low in vitamin D but had adequate iron levels.

18.4% of the women were low in iron but had adequate levels of vitamin D.

3.5% of the women were low in both iron and vitamin D.

RDAs are supposed to be enough to meet the nutrient requirements of 97-98% of healthy individuals, so it is perhaps surprising to see so many women with insufficient levels of iron (21.9%) and/or vitamin D (18.3%) in this study. This could be due to:

Insufficient intake.

- This is a likely explanation for vitamin D because the supplements women were using in this study provided around half the recommended RDA for vitamin D and the women lived at a northern latitude where sun exposure makes a small contribution to vitamin D levels.

- However, this is a less likely explanation for insufficient iron levels because the supplements provided 87% of the RDA for iron.

Inadequate RDAs. Studies like this one provide a rigorous test for the adequacy of existing RDAs. This study suggests the existing RDA for iron is adequate to meet the needs of ~80% of pregnant women, which is reassuring. However, it may need to be increased to reach the goal of meeting the iron requirements for 97-98% of pregnant women.

But the important question is whether the iron and vitamin D insufficiencies seen in this study mattered. The data suggested that they did.

For pregnant women with low iron, but adequate vitamin D levels in the second trimester, there was a small, but significant, increased risk of experiencing depression symptoms in the third trimester.

For pregnant women with low iron and vitamin D levels in the second trimester, the risk of experiencing depression symptoms in the third trimester increased by 2.2 points in the 30-point Edinburg Depression Scale.

- This is equivalent to a 7.4% increased risk of depression from deficiencies of iron and vitamin D alone – and these are only 2 of at least 8 nutrients thought to be associated with maternal depression.

The authors concluded, “Maternal iron and vitamin D biomarkers, measured during midpregnancy, were independently associated with third trimester maternal depression symptoms…This investigation is one of the first to report on the combined adequacy of maternal iron and vitamin D status during pregnancy and its impact on maternal depression.

The novelty of this work reinforces the need to ask similar questions [with other nutrients and] in other pregnant populations. Future investigations should report on the status of multiple nutrients and explore their independent and combined impact on health outcomes of pregnant individuals and their children.”

What Does This Study Mean For You?

Depression during pregnancy is bad for you. And because your fetus can sense your mood, it is bad for your baby. So, what should you do?

You can consult with your doctor about which antidepressants are safe to take during pregnancy. But the truth is there are no good choices. There are some antidepressants that are off limits. There are other antidepressants that appear to have little short-term risks, but we have no idea if there are long-term risks for your child.

So, what about natural approaches? Let’s start with nutrition.

The biggest takeaway from this study is that prenatal supplements may not be sufficient to prevent nutritional deficiencies that may cause prenatal depression for pregnant women.

This does not mean that every pregnant woman suffering prenatal depression should increase their iron and vitamin D levels.

However, if you are experiencing prenatal depression, you might want to ask your doctor about checking your iron and vitamin D status to determine if extra iron and/or vitamin D would be beneficial.

And to put this study into its proper perspective we need to remember that iron and vitamin D deficiencies are only two of many nutrients that may increase the risk of prenatal depression.

For example, in addition to iron and vitamin D, prenatal depression is associated with deficiencies of:

B vitamins, especially folate, B6 and B12. Most prenatal supplements provide the recommended RDA of folate for pregnant women, but not all contain RDA amounts of B6 and B12.

Calcium and magnesium. Very few prenatal supplements provide the recommended RDA for calcium and magnesium.

Omega-3s, especially DHA. Very few prenatal supplements provide DHA, and the few that do usually provide inadequate amounts of DHA.

So, when you are having your nutrition conversation with your doctor, you might not want to limit your conversation to iron and vitamin D.

Alternately, as I suggested last week’s issue of “Health Tips From the Professor”, you might wish to add a multivitamin supplement and an omega-3 supplement providing at least 300 mg of DHA plus EPA. This simple step would be sufficient to assure you have adequate levels of nutrients thought to be important for reducing the risk of prenatal depression.

And, of course, there are other lifestyle factors, as well. For example:

Diets high in highly processed foods are known to increase the risk of depression. And whole food, primarily plant-based diets decrease the risk of depression.

Overweight and obesity increase the risk of depression.

Regular exercise decreases the risk of depression.

The Bottom Line

A recent study looked at whether taking a prenatal supplement was sufficient to eliminate deficiencies of iron and vitamin D during pregnancy and whether deficiencies of these two nutrients during the second trimester of pregnancy increased the risk of depression during the third trimester.

When the investigators looked at iron and vitamin D status during the second trimester:

14.8% of the women were low in vitamin D but had adequate iron levels.

18.4% of the women were low in iron but had adequate levels of vitamin D.

3.5% of the women were low in both iron and vitamin D.

But the important question is whether the iron and vitamin D insufficiencies seen in this study mattered. The data suggested that they did.

For pregnant women with low iron, but adequate vitamin D levels in the second trimester, there was a small, but significant, increased risk of experiencing depression symptoms in the third trimester.

For pregnant women with low iron and vitamin D levels in the second trimester, the risk of experiencing depression symptoms in the third trimester increased by 2.2 points in the 30-point Edinburg Depression Scale.

This is equivalent to a 7.4% increased risk of depression from deficiencies of iron and vitamin D alone.

When you consider that iron and vitamin D are just two of 8 or more nutrients thought to be important for preventing depression during pregnancy, the question becomes what you can do to decrease your risk of developing depression during pregnancy and after the birth of your child.

For more details about the study and what it means for you, 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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My posts and “Health Tips From the Professor” articles carefully avoid claims about any brand of supplement or manufacturer of supplements. However, I am often asked by representatives of supplement companies if they can share them with their customers.

My answer is, “Yes, as long as you share only the article without any additions or alterations. In particular, you should avoid adding any mention of your company or your company’s products. If you were to do that, you could be making what the FTC and FDA consider a “misleading health claim” that could result in legal action against you and the company you represent.

For more detail about FTC regulations for health claims, see this link.

https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance

___________________________________________________________________________

About The Author

Dr. Chaney has a BS in Chemistry from Duke University and a PhD in Biochemistry from UCLA. He is Professor Emeritus from the University of North Carolina where he taught biochemistry and nutrition to medical and dental students for 40 years. Dr. Chaney won numerous teaching awards at UNC, including the Academy of Educators “Excellence in Teaching Lifetime Achievement Award”. Dr Chaney also ran an active cancer research program at UNC and published over 100 scientific articles and reviews in peer-reviewed scientific journals. In addition, he authored two chapters on nutrition in one of the leading biochemistry text books for medical students.

Since retiring from the University of North Carolina, he has been writing a weekly health blog called “Health Tips From the Professor”. He has also written two best-selling books, “Slaying the Food Myths” and “Slaying the Supplement Myths”. And most recently he has created an online lifestyle change course, “Create Your Personal Health Zone”. For more information visit https://chaneyhealth.com.

For the past 45 years Dr. Chaney and his wife Suzanne have been helping people improve their health holistically through a combination of good diet, exercise, weight control and appropriate supplementation.

What Nutrients Are Missing In Prenatal Supplements?

May 7, 2024 by Dr. Steve Chaney

Do These Deficiencies Matter?

Author: Dr. Stephen Chaney

If you are a pregnant mom, nothing is more important than the health of your baby. And if you are pregnant or thinking of becoming pregnant, your doctor has probably recommended a prenatal supplement. But does the prenatal supplement he or she recommended provide you with all the nutrients you need?

In a previous issue of “Health Tips From the Professor” I shared two studies that suggested the answer is, “No”. Those studies concluded that most prenatal supplements had little or no vitamin K, choline, DHA, and iodine – all of which are essential for the health of your newborn baby. And while most prenatal supplements contained calcium, the amount they provided was far below recommended levels.

The authors of the first study also made the point that most women going on a prenatal supplement will probably discontinue taking their multivitamin supplement, so a good prenatal supplement should provide all the essential nutrients.

But they don’t. Folic acid, iron, calcium, and vitamin D have long been recognized as essential for a healthy pregnancy. So, virtually every prenatal supplement contained these four nutrients, although calcium is often present in suboptimal amounts. Beyond those four nutrients, the design of prenatal supplements is haphazard. Some contain vitamin K, choline, iodine, or DHA (often in suboptimal amounts). But almost none contain all four nutrients.

And when you consider the other essential nutrients you find in most multivitamins, prenatal supplements often come up empty. Is that a problem? That’s what this study (KM Godfrey et al, PLOS Medicine, 1-27, December 5, 2023) was designed to find out.

How Was This Study Done?

This was a double-blind, placebo-controlled clinical trial, the gold standard for clinical studies. The investigators recruited 1,729 women who were planning to get pregnant from England, Singapore, and New Zealand between 2015 and 2017.

The women were randomly split into two groups:

The control group received a supplement containing nutrients that were most frequently included in prenatal supplements in those countries (folic acid, iron, calcium, iodine, and beta-carotene).

The intervention group received a supplement containing those nutrients plus riboflavin, vitamin B6, vitamin B12, vitamin D, zinc, inositol, and probiotics).

Riboflavin, vitamin B6, vitamin B12, vitamin D, and zinc were included because they are included in most multivitamins but are often missing in prenatal supplements.

Inositol was included because some studies have suggested that inositol may reduce the risk of maternal hyperglycemia and gestational diabetes.

Blood samples to assess nutritional status were obtained from all women in the study before the trial started (baseline) and after 1 month of supplementation with either the control or intervention formulation.

Of the women entering the study, 512 went on to have a singleton (one child) pregnancy. For these women supplementation was continued until childbirth. Additional blood samples were obtained in early and late pregnancy and at 6 months postdelivery. [Note: no supplementation was provided to either group postdelivery. And this is also a period of time when most women would be breastfeeding.]

The blood samples were tested for:

Blood levels of folic acid, riboflavin, vitamin B6, vitamin B12, and vitamin D.

Functional biomarkers of deficiencies of each of these vitamins.

What Nutrients Are Missing In Prenatal Supplements?

There was no difference in maternal hyperglycemia or gestational diabetes between the control group and the intervention group supplemented with inositol, so I will focus on the other nutrients present in the intervention group.

At baseline when subjects were first entered into the study.

29.2% of the subjects had low or marginal status for folic acid.

82.0% of the subjects had low or marginal status for riboflavin.

1.3% of the subjects had low or marginal status for vitamin B6.

9.1% of the subjects had low or marginal status for vitamin B12.

48.7% of the subjects had low or marginal status for vitamin D.

91.0% of the subjects had low or marginal status for one or more of these vitamins.

In the control group receiving folic acid but no riboflavin, vitaminB6, vitamin B12, and vitamin D:

Folic acid deficiency fell to 4.1% after 1 month of supplementation (the supplement used by the control group contained folic acid), 1% in early pregnancy, 6.1% in late pregnancy, and rose to 31.8% 6 months after supplementation was discontinued. The intervention group got the same amount of folic acid, and their results were similar.

Riboflavin deficiency ranged from 82-92% during pregnancy and returned to 82% 6 months postdelivery.

Vitamin B6 deficiency increased to 54% in late pregnancy and returned to 1.2% 6 months postdelivery.

Vitamin B12 deficiency increased to 55% in late pregnancy and returned to 12.4% 6 months postdelivery.

Vitamin D deficiency ranged from 35-43% during pregnancy and returned to 31% 6 months postdelivery.

Functional markers of vitamin B6 deficiency were evident by late pregnancy.

In short, data from the control group fell into 3 categories:

The data with folic acid confirm previous studies showing that folic acid in the amount present in most prenatal supplements is effective at preventing folic acid deficiency before and during pregnancy. It also strengthens the argument for continuing folic acid supplementation during breastfeeding.

Deficiencies of riboflavin and vitamin D are prevalent in women of childbearing age, but pregnancy does not appear to significantly impact the percentage of women who are deficient in these nutrients.

Deficiencies of vitamins B6 and B12 are rare in women of childbearing age, but pregnancy significantly depletes both nutrients.

- This was particularly evident for vitamin B6. Blood levels of vitamin B6 markers decreased to a level that could impact the functioning of vitamin B6-depended metabolic pathways.

For the intervention group receiving additional riboflavin, vitamin B6, vitamin B12, and vitamin D:

Deficiencies of these vitamins were eliminated by one month of supplementation.

Vitamin levels remained adequate during pregnancy.

Except for vitamin B12, deficiencies of these vitamins reappeared when supplementation was discontinued for 6 months. The maintenance of adequate B12 levels 6 months after supplementation stopped was expected because the body holds on to its B12 stores very tightly.

In short deficiencies of these nutrients before and during pregnancy could be eliminated by supplementation with levels of these nutrients found in many multivitamins.

The authors concluded, “Over 90% of the trial participants had low concentrations of one or more of folate, riboflavin, vitamin B12, or vitamin D during preconception, and many developed markers of vitamin B6 deficiency in late pregnancy. Preconception/pregnancy supplementation in amounts available in over-the-counter supplements substantially reduces the prevalence of vitamin deficiency and depletion markers before and during pregnancy, with higher maternal plasma vitamin B12 maintained during the recommended lactation period.”

Do These Deficiencies Matter?

It is well established that deficiencies of folic acid and vitamin D cause health risks for the mother and developmental risks for the fetus, so I won’t discuss these nutrients here.

However, the effect of riboflavin, vitamin B6, and vitamin B12 deficiencies on pregnancy is less well known, which is probably why these nutrients are often not added to prenatal supplements.

The authors of the study said small studies have suggested that:

Low or deficient riboflavin status may be associated with a higher risk of anemia during pregnancy.

Low vitamin B6 status may be associated with an increased risk of preterm birth and development of metabolic health risks in the child.

Low vitamin B12 status may be associated with increased risk of gestational diabetes and pre-eclampsia in the mother, and increased risk of neural tube defects, preterm birth, low birth weight, and neurocognitive delays in the baby – with the strongest evidence being an effect on neurocognitive development.

While none of these risks have been definitively proven, the authors point out that deficiencies of these nutrients can easily be eliminated with inexpensive, over-the-counter multivitamin supplements.

What Does This Study Mean For You?

Perhaps I should start this section by asking why these deficiencies are so common in women of child-bearing age.

The authors speculate that part of the reason is that many women are giving up meat (B12 and iron) and dairy (calcium and riboflavin) for health or environmental reasons.

However, they also point out that a more likely cause is that more than 60% of calories consumed in countries like England, New Zealand, and the United States comes from ultra-processed foods – otherwise known as “empty calories”.

Whatever the cause, the authors conclude, “…the findings suggest a need to reappraise dietary recommendations for preconception and pregnancy to consider further the role of multiple micronutrient supplements for women living in higher-income countries.” I agree.

In a previous “Health Tips From the Professor” article, I reported a recent study showing that most prenatal supplements have either no or inadequate amounts of vitamin K, choline, DHA, iodine, and calcium, nutrients that are absolutely essential for a healthy pregnancy. And I gave recommendations for choosing the best prenatal supplement for you and your child.

That study also noted that many women discontinue their multivitamin supplement when they start taking a prenatal supplement. The current study indicates that practice may be unwise. It shows that:

Many women of childbearing age are deficient in one or more of these essential nutrients, and…

Essential nutrients not found in most prenatal supplements may also be important for a healthy pregnancy.

So, if you are pregnant or thinking of becoming pregnant, follow this article’s recommendation to start with a well-designed prenatal supplement that provides adequate amounts of folate, iron, calcium, vitamin D, vitamin K, choline, DHA, and iodine and add a multivitamin supplement that provides the other essential nutrients. Alternatively, a simpler approach would be to choose a well-designed prenatal supplement that includes all the essential nutrients. That would be my recommendation.

I would also note this study showed that deficiencies of most of these nutrients reappeared as soon as supplementation was discontinued. Although the authors of this study did not mention it, this reinforces the importance of continuing supplementation during breastfeeding.

The Bottom Line

I have previously reported on a study that concluded many prenatal supplements lack one or more nutrients shown to be important for a healthy pregnancy. But let’s say you have found a prenatal supplement that provides all those nutrients. Is that enough?

Studies show that most women stop taking their multivitamin supplement when they start on a prenatal supplement. But is that a good idea? Are there essential nutrients found in multivitamins, but not in many prenatal supplements that are also important for a healthy pregnancy?

A recent study asked that question in women who were trying to become pregnant. The study found that:

Many women of childbearing age are deficient in one or more essential nutrients found in multivitamin supplements but often missing in prenatal supplements, and…

Essential nutrients not found in most prenatal supplements may also be important for a healthy pregnancy.

For more details about this study and what it means for you 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.

______________________________________________________________________________

For more detail about FTC regulations for health claims, see this link.

https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance

______________________________________________________________________

About The Author

Which Vitamins Reduce Breast Cancer Risk?

May 30, 2023 by Dr. Steve Chaney

How Can You Reduce Your Risk Of Breast Cancer?

Author: Dr. Stephen Chaney

Breast cancer is scary. The good news is that treatment has gotten much better. Breast cancer is no longer a death sentence. But most women would prefer to avoid breast cancer surgery, radiation, and/or chemotherapy if they could.

Could something as simple as supplementation reduce your risk of developing breast cancer? If so, which vitamins should you be taking? Or, put another way, which vitamins reduce breast cancer risk?

If you ask your doctor, they will tell you, “Supplementation is a waste of money. Vitamins don’t reduce your risk of getting cancer.” And they will be correct! That’s because these are the wrong questions.

Let me explain. These are “one size fits all” questions. Studies to answer these questions start with healthy women and asks if vitamin supplementation reduces breast cancer risk for all of them. The answer to that question is, “No”. Multiple studies have confirmed this.

But the truth is more complicated. We should be asking, “Who benefits from vitamin supplementation”, instead of, “Does everyone benefit from supplementation?”

I have summed up this concept with the Venn diagram on the right. Every woman does not need supplementation. But those with poor diet, increased need, genetic predisposition, and/or certain diseases may benefit from supplementation. That is why we should be asking, “Who needs supplementation?”.

Unfortunately, while this concept of individualized treatment has led to dramatic advances for cancer drug development, it has been virtually ignored for studies on supplementation and breast cancer risk.

The current study (H Song et al., Nutrients, 14: 2644, 2022) is an exception. It asks whether obese women who wish to reduce their risk of breast may benefit more from certain micronutrients than women of normal weight.

How Was This Study Done?

The data for this analysis came from the KoGES study. This was a study administered by the Korea Agency for Disease Control and Prevention between 2004 and 2016. It was designed to provide a scientific basis for personalized prevention of chronic diseases in the Korean population.

Of the 211,721 participants enrolled in the original KoGES study, this study included data from 41,593 women who:

Underwent a health examination at 38 health examination centers upon enrollment between 2004 and 2013 and a follow up health examination between 2012 and 2016. The average follow-up period was 4.9 years.

Were cancer-free when they enrolled in the study and developed breast cancer prior to their follow-up health examination.

Had reliable diet data.

Dietary intake was based on a food frequency questionnaire administered during their initial health screening. Dietary intake of 15 micronutrients (calcium, phosphorous, iron, potassium, vitamin A, sodium, vitamin B1, vitamin B2, vitamin B6, niacin, folic acid, vitamin C, vitamin E, zinc, and cholesterol) and 4 macronutrients (energy, protein, fat, and carbohydrate) was determined from the food frequency data and compared to the Korean Dietary Reference Intakes (KDRIs). [Note: The Korean DRIs are slightly different than US standards.]

The women were then divided into two groups based on whether they consumed more or less than the Korean DRIs for each nutrient.

Which Vitamins Reduce Breast Cancer Risk?

There were two major findings from this study.

1) When the investigators grouped all the women in the study together:

- none of the 15 micronutrients and 4 macronutrients analyzed in this study influenced breast cancer risk.

- This confirms most previous studies that have been designed as a “one size fits all” study. So, if your doctor was relying on this kind of study, they were technically correct in saying that vitamin supplements don’t appear to reduce breast cancer risk.

2) But when the investigators separated the women by weight, an interesting dichotomy was observed:

- For obese women (BMI ≥ 25 kg/m²):

- - Vitamin C intake above the recommended Korean DRI (100 mg/day) reduced the risk of breast cancer by 46%.

- - Vitamin B6 intake above the recommended Korean DRI (1.4 mg/day) reduced the risk of breast cancer by 52%.

- For women of normal weight (BMI < 25 kg/m²) neither vitamin C nor vitamin B6 had any effect on breast cancer risk.

The authors concluded, “In obese women, exceeding the recommended daily intake levels of vitamin C and vitamin B6 was associated with a lower risk of breast cancer. However, other micronutrients were not associated with breast cancer risk in these women.” [Note: Supplement use was not included in the diet survey, so above recommended intake of C and B6 was from foods consumed, not from supplements.]

What Does This Study Mean For You?

This study is a perfect example of why we should be asking, “Who benefits from vitamin supplementation”, instead of, “Does everyone benefit from supplementation?”

In terms of the Venn diagram I introduced above, some people consider obesity a disease.

But whether you consider obesity a disease or not, it does increase the need for many nutrients. So, it is conceivable that extra vitamins C and B6 might provide benefits in obese women that are not seen in non-obese women.

This is, of course, a ground-breaking study. It is the first study of its kind and deserves to be followed by other studies to confirm this observation. Ideally, these studies would test whether the same effect is seen in other population groups and determine the optimal dose of vitamin C and B6 to reduce breast cancer risk.

However, I am not optimistic that these studies will be done. It is easy to get funding for the “do vitamin supplements benefit everyone?” studies that confirm the existing prejudice against vitamin supplementation.

It is much harder to obtain funding for “who benefits from vitamin supplementation?” studies that challenge the existing paradigm. But these are the kind of studies that are needed most.

How Can You Reduce Your Risk Of Breast Cancer?

As I said, this is the first study of its kind, so you could consider the results as preliminary. However, assuming it might be true:

I do not recommend megadoses of vitamins C and B6. The above average intake of C and B6 in this study came from food alone. And we do not have any dose response studies that might define an optimal dose of C and B6.

I do recommend balance. Based on this study, multivitamins should provide enough C and B6 to have a meaningful effect on breast cancer risk. And multivitamins are inexpensive and risk-free.

In addition, there are things you can do that are proven to reduce breast cancer risk. Here is what the American Cancer Society recommends:

Get to and stay at a healthy weight.

Be physically active and avoid time sitting.

Follow a healthy eating plan.

It is best not to drink alcohol.

Think carefully about using hormone replacement therapy.

I provide more detail about each of these recommendations in a recent article in “Health Tips From the Professor”.

The Bottom Line

Most doctors will tell you that supplementation does not reduce your risk of breast cancer. And that opinion is backed up by multiple published clinical studies.

But the problem is that these studies are all asking the wrong question. They are asking, “Does supplementation reduce the risk of breast cancer for all women?”. A better question would be, “Which women benefit from supplementation?”

A recent study asked both of those questions. They looked at the effect of 15 micronutrients on breast cancer risk.

When the investigators grouped all the women in the study together:

- None of the 15 micronutrients influenced breast cancer risk.

2) But when the investigators separated the women by weight, an interesting dichotomy was observed:

- For obese women (BMI ≥ 25 kg/m²):

- - Vitamin C intake above the recommended intake reduced the risk of breast cancer by 46%.

- - Vitamin B6 intake above the recommended intake reduced the risk of breast cancer by 52%.

- For women of normal weight (BMI < 25 kg/m²) neither vitamin C nor vitamin B6 had any effect on breast cancer risk.

For more information on this study, what it means for you, and proven methods for reducing breast cancer risk 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.

____________________________________________________________________________

For more detail about FTC regulations for health claims, see this link.

https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance

Prenatal Supplements Strike Out Again

May 9, 2023 by Dr. Steve Chaney

Is It Three Strikes And You Are Out?

Author: Dr. Stephen Chaney

If you are pregnant, you want the best for your unborn baby. Your doctor has recommended a prenatal supplement, but do the prenatal supplements on the market meet your needs? A few months ago, I shared two studies that concluded that most prenatal supplements on the market are woefully inadequate.

In fact, the authors said, “[Our] analysis found that prenatal supplements vary widely in content, often only contain a subset of essential vitamins, and the levels were often below…recommendations.”

In other words, their study found that most prenatal vitamins on the market may not be adequate to support your needs and the needs of your child through pregnancy and breastfeeding.

Now, a third study on the topic has been published (KA Saunders et al, American Journal of Clinical Nutrition, 117: 823-829, 2023. It differs from the previous studies in that:

1) The previous two studies took a comprehensive approach, while this study focused on 6 key nutrients.

The previous studies included all nutrients important for a healthy pregnancy including choline, iodine, and vitamin K, which have only recently been shown to be important for a healthy pregnancy.

This study focused on 6 nutrients, vitamin A, vitamin D, folic acid, calcium, iron, and omega-3 fatty acids, which have long been recognized as essential for a healthy pregnancy.

2) The previous two studies focused on prenatal supplements, while this study focused on all supplements that might be taken by pregnant women.

3) The previous two studies asked whether supplements provided recommended amounts of all nutrients needed for a healthy pregnancy. This study took a “Goldilocks approach” and asked whether levels of these 6 essential nutrients were appropriate (“just right”). The study:

Started by determining the intake of these 6 key nutrients by American women. The authors of the study then added the amount of each nutrient provided by the supplements in their study to the amount of that nutrient in the diet of American women and:

- Calculated the minimum amount of each nutrient that would be needed to assure that 90% of American women taking a particular supplement would meet the recommended intake for pregnant and lactating women.

- Calculated the maximum amount of each nutrient provided by supplements in their study to assure that that 90% of American women taking that supplement would not get potentially toxic amounts of that nutrient.

In other words, for each of the 6 nutrients they calculated a supplemental dose range that was neither too low nor too high. They called this the “appropriate dose range” for each nutrient. Goldilocks would have called it “just right”.

I’m sure you are anxiously waiting to learn what their study found. But before we go there, I will describe how the study was done.

How Was The Study Done?

For the dietary intake portion of the study, the authors used dietary intake data previously collected from the Environmental Influences on Child Health Outcomes (ECHO) study.

The ECHO study is a consortium of 69 medical centers across multiple states. It is an observational study of mothers and their offspring designed to understand the effects of early life exposures on child health and development.

The current study analyzed dietary intake data for 2450 participants from 6 medical centers across 5 states in the ECHO study. The women in this study were diverse with respect to ethnicity, education, and weight.

All pregnant women in the current study completed at least one 24-hour dietary recall between 6-week gestation until delivery (24% completed one dietary recall. 76% completed two or more dietary recalls). Dietary intake was generally assessed with an expert interviewer and included all foods and beverages consumed in the previous 24 hours.

For the supplement portion of the study, the authors used the NIH Dietary Supplement Label Database because it is the most complete listing of supplements in the US. The authors selected 20,547 supplements that contained at least one of the 6 essential nutrients from this database.

To determine which of the 20,547 supplements contained appropriate levels of the 6 nutrients (vitamin A, vitamin D, folic acid, calcium, iron, and omega-3 fatty acids) selected for this study, the authors used the process described in the introduction above. Briefly:

The authors added the amount of each nutrient provided by the supplements in their study to the amount of that nutrient in the diet of American women and:

Calculated the minimum amount of each nutrient that would be needed to assure that 90% of American women taking a particular supplement would meet the recommended intake for pregnant and lactating women.

Calculated the maximum amount of each nutrient provided by supplements in their study to assure that that 90% of American women taking that supplement would not get potentially toxic amounts of that nutrient.

In other words, for each of the 6 nutrients they calculated a supplemental dose range that was neither too low nor too high. They called this the “appropriate dose range” for each nutrient.

Why Are The 6 Nutrients Included In This Study Important?

Dietary Intake Is Often Inadequate

The diet analysis of pregnant American women in this study found:

42% were at risk of inadequate vitamin A intake.

96% were at risk of inadequate vitamin D intake.

45% were at risk of inadequate folic acid intake.

55% were at risk of inadequate calcium intake.

93% were at risk of inadequate iron intake.

67% were at risk of inadequate omega-3 intake.

The percentage of women at risk for inadequate intake of these nutrients varied with age, ethnicity, and income levels. But the overall message is clear. Most American women are not getting enough of these essential nutrients from their diet alone.

The Risk of Inadequate and Excessive Intake Of These Nutrients

These 6 nutrients were chosen in part because reviews by the Cochrane Collaboration have concluded that inadequate intake of these nutrients are associated with complications during pregnancy and delivery. They can also adversely affect the health and normal development of the baby.

This is important because the Cochrane Collaboration is considered the Gold Standard of clinical studies. You can find a more detailed description of Cochrane Collaboration studies and why they are the Gold standard here.

[Note: The Cochrane Collaboration has not yet evaluated choline, iodine, and vitamin K for pregnant women, but their inclusion in prenatal supplements is supported by multiple clinical studies.]

In addition, excess intake of all these nutrients except omega-3s can harm both the fetus and the mother. The is why the Food and Nutrition Board has set ULs (Upper Limits – the level above which toxicity can occur) for 5 of the 6 nutrients. This is important because previous studies have suggested that up to 25% of women may be getting toxic levels of one or more of these nutrients when you consider both their dietary intake and their prenatal supplement.

Summary

In other words, both too little and too much of these nutrients can harm the mom and her baby. It is critical that prenatal supplements get the dosing right.

It is for that reason that the authors of this study have set an “appropriate dose range” (high enough that 90% of women have enough of each nutrient to prevent deficiency and low enough that 90% of women do not exceed the UL for each nutrient) as the standard for evaluating the adequacy and safety of supplements for pregnant women.

Prenatal Supplements Strike Out Again

Of the 20,547 supplements (421 labeled as prenatal supplements) available on the US market as of December 31, 2022, the investigators reported that:

Only 69 (0.3%) supplements contained all 6 nutrients considered essential for a healthy pregnancy.

Only 1 supplement contained all 6 nutrients at the appropriate doses, and it wasn’t even labeled as a prenatal supplement.

In addition:

One supplement containing all 6 nutrients put 100% of the women in their study at risk for excessive intake of folic acid.

Another supplement containing all 6 nutrients put 46% of the women in their study at risk of inadequate calcium intake.

The authors concluded, “Almost no US dietary supplements provide key nutrients in the doses needed for pregnant women. Affordable and convenient products that fill the gap between food-based intake and estimated requirements of pregnancy without inducing excess intake are needed to support pregnant women and their offspring.”

In short, the conclusion of this study can be summed up as, “Prenatal Supplements Strike Out Again”.

[Note: It sometime takes a while for supplement labels to be posted in the NIH Dietary Supplement Label Database. The authors acknowledged that this study may not include supplements introduced or reformulated in the last quarter of 2022.]

Is It Three Strikes And You Are Out?

If you are pregnant or thinking of becoming pregnant, this should be a wake-up call.

70% of pregnant women in this country take prenatal supplements, usually based on recommendations by their health care provider. They assume the prenatal supplements meet their needs and the needs of their unborn baby.

Yet three studies evaluating the adequacy of prenatal supplements have been published in the past few months. They took very different approaches in evaluating the supplements. But all three studies concluded that the vast majority of prenatal supplements on the market are woefully inadequate.

You may be wondering, “Is it three strikes, and you are out?” Are there no decent prenatal supplements on the market? The answer to those questions is, “No. There are good prenatal supplements on the market.”

You may be wondering how I can say that in the face of such overwhelming negative data. That’s because while all 3 studies were very good studies, they each had “blind spots”:

1) Each of the studies used very stringent criteria for identifying adequate prenatal supplements. In some cases, their criteria were stricter than the RDA recommendations and the recommendations of the American College of Obstetrics and Gynecology for pregnant and lactating women. It could be argued that their criteria were too stringent.

2) In the case of the current study, it could also be argued that evaluating only 6 nutrients is not a good criterion for evaluating the adequacy of prenatal supplements. For example, I looked up the one supplement rated as adequate in this study. It does provide appropriate doses of the 6 nutrients this study focused on. It also provides appropriate doses of vitamin K and iodine. But it does not provide choline. It is a very good supplement for women, but it is not the perfect prenatal supplement.

So, what can you do? How can you find the best prenatal supplement for you? Unfortunately, you cannot rely on advice from your friends or your health professional. You cannot rely on advertisements. That is a good place to start, but you have to do your own sleuthing.

With that in mind, I have listed 7 simple rules for selecting the best possible prenatal supplement in my article about the first two studies. Use these rules for evaluating every prenatal supplement you come across. Happy sleuthing.

The Bottom Line

A recent study evaluated all 20,547 supplements on the US market to see if they met the needs of pregnant women in this country.

They focused on 6 nutrients (vitamin A, vitamin D, folic acid, calcium, iron, and omega-3s) known to be essential for a healthy pregnancy.

They determined the dietary intake for all 6 nutrients in a cross section of pregnant women in the US.

They added the amount of the 6 nutrients in each of the 20,547 supplements to the dietary intake of those nutrients by pregnant women.

They then asked which supplements provided the “appropriate dose” of all 6 nutrients. They defined “appropriate dose” as the dose range that was.

- High enough to prevent deficiency of that nutrient in 90% of pregnant women taking the supplement…and…

- Low enough to prevent toxicity from that nutrient in 90% of pregnant women taking the supplement.

In other words, for each of the 6 nutrients they calculated a supplemental dose range that was neither too low nor too high.

Of the 20,547 supplements (421 labeled as prenatal supplements) available on the US market:

Only 69 (0.3%) supplements contained all 6 nutrients they considered essential for a healthy pregnancy.

Only 1 supplement contained all 6 nutrients at the appropriate doses, and it wasn’t even labeled as a prenatal supplement.

If you are pregnant or thinking of becoming pregnant, this should be a wake-up call.

Yet three studies evaluating the adequacy of prenatal supplements have been published in the past few months. And all three studies concluded that the vast majority of prenatal supplements on the market are woefully inadequate.

You may be wondering how I can say that in the face of such overwhelming negative data. That’s because while all 3 studies were very good studies, they each had “blind spots”:

For more details on this study and 7 tips on finding the best prenatal supplement for you, 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.

____________________________________________________________________________

For more detail about FTC regulations for health claims, see this link.

https://www.ftc.gov/business-guidance/resources/health-products-compliance-guidance

Which Supplements Are Good For Your Heart?

February 7, 2023 by Dr. Steve Chaney

How Should You Interpret This Study?

Author: Dr. Stephen Chaney

February is Heart Health month. So, it is fitting that we ask, “What is the status of heart health in this country?” The American Heart Association just published an update of heart health statistics through 2019 (CW Tsao et al, Circulation, 145: e153-e639, 2022). And the statistics aren’t encouraging. [Note: The American Heart Association only reported statistics through 2019 because the COVID-19 pandemic significantly skewed the statistics in 2020 and 2021].

The Good News is that between 2009 and 2019:

All heart disease deaths have decreased by 25%.
Heart attack deaths have decreased by 6.6%.
Stroke deaths have decreased by 6%.

The Bad News is that:

Heart disease is still the leading cause of death in this country.
Someone dies from a heart attack every 40 seconds.
Someone dies from a stroke every 3 minutes.

Diet, exercise, and weight control play a major role in reducing the risk of heart disease. Best of all, they have no side effects. They represent a risk-free approach that each of us can control.

But is there something else? Could supplements play a role? Are supplements hype or hope for a healthy heart?

All the Dr. Strangeloves in the nutrition space have their favorite heart health supplements. They claim their supplements will single-handedly abolish heart disease (and help you leap tall buildings in a single bound).

On the other hand, many doctors will tell you these supplements are a waste of money. They don’t work. They just drain your wallet.

It’s so confusing. Who should you believe? Fortunately, a recent study (P An et al, Journal of the American College of Cardiology, 80: 2269-2285, 2022) has separated the hype from the hope and tells us which “heart-healthy” supplements work, and which don’t.

How Was This Study Done?

This was a major clinical study carried out by researchers from the China Agricultural University and Brown University in the US. It was a meta-analysis, which means it combined the data from many published clinical trials.

The investigators searched three major databases of clinical trials to identify:

884 randomized, placebo-controlled clinical studies…

Of 27 types of micronutrients…

With a total of 883,627 patients…

Looking at the effectiveness of micronutrient supplementation lasting an average of 3 years on either…

- Cardiovascular risk factors like blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides…or…

- Cardiovascular outcomes such as coronary heart disease (CHD), heart attacks, strokes, and deaths due to cardiovascular disease (CVD) and all causes.

[Note: Coronary heart disease (CHD) refers to build up of plaque in the coronary arteries (the arteries leading to the heart). It is often referred to as heart disease and can lead to heart attacks (myocardial infarction). Cardiovascular disease (CVD) is a more inclusive term that includes coronary heart disease, stroke, congenital heart defects, and peripheral artery disease.]

The investigators also included an analysis of the quality of the data in each of the clinical studies and rated the evidence of each of their findings as high quality, moderate quality, or low quality.

Which Supplements Are Good For Your Heart?

The top 3 heart-healthy supplements in this study were:

Omega-3 Fatty Acids:

Increased HDL cholesterol and decreased triglycerides, both favorable risk factors for heart health.
Deceased risk of heart attacks by 15%, all CHD events by 14%, and CVD deaths by 7% (see definitions of CHD and CVD above).
The median dose of omega-3 fatty acids in these studies was 1.8 g/day.
The evidence was moderate quality for all these findings.

Folic Acid:

Decreased LDL cholesterol (moderate quality evidence) and decreased blood pressure and total cholesterol (low quality evidence).
Decreased stroke risk by 16% (moderate quality evidence).

Coenzyme Q10:

Decreased triglycerides (high quality evidence) and reduced blood pressure (low quality evidence).
Decreased the risk of all-cause mortality by 32% (moderate quality evidence).
These studies were performed with patients diagnosed with heart failure. Coenzyme Q10 is often recommended for these patients, so the studies were likely performed to test the efficacy of this treatment.

There were three micronutrients (vitamin C, vitamin E, and vitamin D) that did not appear to affect heart disease outcomes.

Finally, as reported in previous studies, β-carotene increased the risk of stroke, CVD mortality, and all-cause mortality.

In terms of the question I asked at the beginning of this article, this study concluded that:

Omega-3, folic acid, and coenzyme Q10 supplements represent hope for a healthy heart.
Vitamin C, vitamin E, and vitamin D supplements represent hype for a healthy heart.
β-carotene supplements represent danger for a healthy heart.

But these conclusions just scratch the surface. To put them into perspective we need to dig a bit deeper.

How Should You Interpret This Study?

In evaluating the significance of these findings there are two things to keep in mind.

#1: This study is a meta-analysis and meta-analyses have both strengths and weaknesses.

The strength of meta-analyses is that by combining multiple clinical studies they can end up with a database containing 100s of thousands of subjects. This allows them to do two things:

It allows the meta-analysis to detect statistically significant effects that might be too small to detect in an individual study.
It allows the meta-analysis to detect the average effect of all the clinical studies it includes.

The weakness of meta-analyses is that the design of individual studies included in the analysis varies greatly. The individual studies vary in things like dose, duration, type of subjects included in the study, and much more.

This is why this study rated most of their conclusions as backed by moderate- or low-quality evidence. [Note: The fact that the authors evaluated the quality of evidence is a strength of this study. Most meta-analyses just report their conclusions without telling you how strong the evidence behind those conclusions is.]

#2: Most clinical studies of supplements (including those included in this meta-analysis) have two significant weaknesses.

Most studies do not measure the nutritional status of their subjects prior to adding the supplement. If their nutritional status for a particular nutrient was already optimal, there is no reason to expect more of that nutrient to provide any benefit.
Most studies measure the effect of a supplement on a cross-section of the population without asking who would be most likely to benefit.

You would almost never design a clinical study that way if you were evaluating the effectiveness of a potential drug. So, why would you design clinical studies of supplements that way?

With these considerations in mind, let me provide some perspective on the conclusions of this study.

Coenzyme Q10:

This meta-analysis found that coenzyme Q10 significantly reduced all-cause mortality in patients with heart failure. This is consistent with multiple clinical studies and a recent Cochrane Collaboration review.

Does coenzyme Q10 have any heart health benefits for people without congestive heart failure? There is no direct evidence that it does, but let me offer an analogy with statin drugs.

Statin drugs are very effective at reducing heart attacks in high-risk patients. But they have no detectable effect on heart attacks in low-risk patients. However, this has not stopped the medical profession from recommending statins for millions of low-risk patients. The rationale is that if they are so clearly beneficial in high-risk patients, they are “probably” beneficial in low-risk patients.

I would argue a similar rationale should apply to supplements like coenzyme Q10.

Omega-3s:

This study found that omega-3 reduced both heart attacks and the risk of dying from heart disease. Most previous meta-analyses of omega-3s and heart disease have come to the same conclusion. However, some meta-analyses have failed to find any heart health benefits of omega-3s. Unfortunately, this has allowed both proponents and opponents of omega-3 use for heart health to quote studies supporting their viewpoint.

However, there is one meta-analysis that stands out from all the others. A group of 17 scientists from across the globe collaborated in developing a “best practices” experimental design protocol for assessing the effect of omega-3 supplementation on heart health. They conducted their clinical studies independently, and when their data (from 42,000 subjects) were pooled, the results showed that omega-3 supplementation decreased:

Premature death from all causes by 16%.
Premature death from heart disease by 19%.
Premature death from cancer by 15%.
Premature death from causes other than heart disease and cancer by 18%.

This study eliminates the limitations of previous meta-analyses. That makes it much stronger than the other meta-analyses. And these results are consistent with the current meta-analysis.

Omega-3s have long been recognized as essential nutrients. It is past time to set Daily Value (DV) recommendations for omega-3s. Based on the recommendations of other experts in the field, I think the DV should be set at 500-1,000 mg/day. I take more than that, but this would represent a good minimum recommendation for heart health.

Folic acid:

As with omega-3s, this meta-analysis reported a positive effect of folic acid on heart health. But many other studies have come up empty. Why is that?

It may be because, between food fortification and multivitamin use, many Americans already have sufficient blood levels of folic acid. For example, one study reported that 70% of the subjects in their study had optimal levels of folates in their blood. And that study also reported:

Subjects with adequate levels of folates in their blood received no additional benefit from folic acid supplementation.
However, for subjects with inadequate blood folate levels, folic acid supplementation decreased their risk of heart disease by ~15%.

We see this pattern over and over in supplement studies. Supplement opponents interpret these studies as showing that supplements are worthless. But a better interpretation is that supplements benefit those who need them.

The problem is that we don’t know our blood levels of essential nutrients. We don’t know which nutrients we need, and which we don’t. That’s why I like to think of supplements as “insurance” against the effects of an imperfect diet.

Vitamins E and D:

The situation with vitamins E and D is similar. This meta-analysis found no heart health benefit of either vitamin E or D. That is because the clinical studies included in the meta-analysis asked whether vitamin E or vitamin D improved heart health for everyone in the study.

Previous studies focusing on patients with low blood levels of these nutrients and/or at high risk of heart disease have shown some benefits of both vitamins at reducing heart disease risk.

So, for folic acid, vitamin E, and vitamin D (and possibly vitamin C) the take-home message should be:

Ignore all the Dr. Strangeloves telling you that these vitamins are “magic bullets” that will dramatically reduce your risk of heart disease.
Ignore the naysayers who tell you they are worthless.
Use supplementation wisely to make sure you have the recommended intake of these and other essential nutrients.

β-carotene:

This meta-analysis reported that β-carotene increased the risk of heart disease. This is not a new finding. Multiple previous studies have come to the same conclusion.

And we know why this is. There are many naturally occurring carotenoids, and they each have unique heart health benefits. A high dose β-carotene supplement interferes with the absorption of the other carotenoids. You are creating a deficiency of other heart-healthy carotenoids.

If you are not getting lots of colorful fruits and vegetables from your diet, my recommendation is to choose a supplement with all the naturally occurring carotenoids in balance – not a pure β-carotene supplement.

The Bottom Line

The Dr. Strangeloves in the nutrition space all have their favorite heart health supplements. They claim their supplements will single-handedly abolish heart disease (and help you leap tall buildings in a single bound).

On the other hand, many doctors will tell you these supplements are a waste of money. They don’t work. They just drain your wallet.

It’s so confusing. Who should you believe? Fortunately, a recent study has separated the hype from the hope and tells us which “heart-healthy” supplements work, and which don’t.

This study was a meta-analysis of 884 clinical studies with 883,627 participants. It reported:

Omega-3 supplementation deceased risk of heart attacks by 15% and all cardiovascular deaths by 7%.
Folic acid supplementation decreased stroke risk by 16%.
Coenzyme Q10 supplementation decreased the risk of all-cause mortality in patients with heart failure by 32%.
Vitamin C, vitamin E, vitamin D did not appear to affect heart disease outcomes.
β-carotene increased the risk of stroke, CVD mortality, and all-cause mortality.

For more details on this study and what it means for you, 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.

Do Supplements Interfere With Chemotherapy?

February 2, 2021 by Dr. Steve Chaney

Should You Avoid Supplement Use During Chemotherapy?

Since much of my research career was devoted to cancer research, specifically developing new chemotherapeutic drugs for treating cancer, many of you have asked me the question: “Do food supplements interfere with chemotherapy?”

My answer has always been that it is theoretically possible, but that we don’t really know the answer because the necessary studies have not been done.

However, I do know that most cancer drugs are retained in the body for a short period of time. So, my pragmatic advice has always been to avoid supplementation for a day or two before to a day or two after each round of chemotherapy. That is a strategy designed to minimize the possibility that supplementation would interfere with chemotherapy and maximize the possibility that supplementation might aid in recovery between rounds of chemotherapy.

That is why I was interested when I saw the recent headlines claiming certain supplements may interfere with chemotherapy for breast cancer. I wanted to find out if someone had finally done a definitive study on the effect of supplementation on chemotherapy.

So, I have reviewed the study (CB Ambrosone et al, Journal of Clinical Oncology, 38, 804-815, 2020) behind the headlines and will share what I discovered.

How Was The Study Done?

This study was an offshoot of a much larger Phase III clinical trial designed to determine the best schedule for administering three drugs (doxorubicin, cyclophosphamide, and paclitaxel) to patients with high-risk early-stage breast cancer.

The 1,134 patients enrolled in this study were given questionnaires on their use of supplements when they registered for the study to determine supplement use prior to the study. They were also given questionnaires when they completed chemotherapy to determine supplement use during chemotherapy.

The questionnaires documented use of:

Multivitamins

The antioxidants vitamin C, vitamin A, vitamin E, carotenoids, and coenzyme Q10.

Vitamin D.

The B vitamins vitamin B6, vitamin B12, and folic acid.

The minerals iron and calcium.

Omega-3 fatty acids.

Glucosamine, melatonin, and acidophilus.

Recurrence of the breast cancer and death from breast cancer were measured 6 months after chemotherapy ended.

Do Supplements Interfere With Chemotherapy?

The study reported:

The number of patients using individual antioxidant supplements was too low to determine whether individual antioxidants had any effect on treatment outcomes.

When the patients using any antioxidant supplement were pooled into a single group, there was a nonsignificant association between antioxidant supplement use during chemotherapy and an increased risk of breast cancer recurrence and death from breast cancer.

Iron use during chemotherapy was significant associated with an increased risk of breast cancer recurrence.

Vitamin B12 use during chemotherapy was significantly associated with increased risk of breast cancer recurrence and death from breast cancer.

Multivitamin use was not associated with either recurrence or death from breast cancer.

The number of patients using the other supplements was too low to determine whether those supplements had any effect on treatment outcomes.

The authors concluded: “Associations between survival outcomes and use of antioxidant and other dietary supplements are consistent with recommendations for caution among patients when considering the use of supplements, other than a multivitamin, during chemotherapy.”

This is the conclusion that generated the headlines you may have seen.

However, in their discussion the authors conceded that a previous review concluded that, “…insufficient evidence existed with regard to the safety of dietary supplements [during chemotherapy] to make recommendations, and that still may be the case.”

I will discuss the reasons for their disclaimer below. However, I will point out that disclaimers like this never seem to make it into the headlines you read.

What Are The Strengths And Weaknesses Of This Study?

The only strength of this study is that it was performed in the context of an ongoing clinical trial, with surveys conducted before chemotherapy and during chemotherapy to assess supplement use.

However, the study had multiple weaknesses that limit the ability to draw any firm conclusions from the study.

#1: The number of people using supplements in this study was very small. For example:

Only 200 people took any antioxidants during chemotherapy.

Only 137 people took a vitamin B12 supplement during chemotherapy.

Only 109 people took an iron supplement during chemotherapy.

To put this into perspective, if a drug company were submitting a new drug for approval to the FDA, they would be required to submit data from ~50-100-fold more cancer patients to prove that the drug was effective.

With this small number of supplement users, even “statistically significant” observations are questionable.

In contrast, the number of people taking a multivitamin during chemotherapy was 497. Thus, those data were a little stronger than the data for individual supplements.

#2: They did not ask why people were taking supplements. It turns out that the patients who used supplements were older and sicker. They were more likely to be overweight and to have type 2 diabetes.

These are patients who are also more likely to have poor outcomes from chemotherapy. The authors tried to correct for that, but it is virtually impossible to make these corrections when the number of patients taking supplements is so low.

#3: They did not ask about the dose of supplements people were taking.

Multivitamins typically contain RDA levels of antioxidants and vitamin B12, so it would be safe to assume that RDA levels of antioxidants and vitamin B12 are safe during chemotherapy.

Approximately 50% of the women in the study were premenopausal, so it is likely that they were taking a multivitamin with iron. That suggests that RDA levels of iron are safe during chemotherapy for premenopausal women.

In short, the association between supplement use and poorer outcomes from chemotherapy is tenuous. If there is any association, it is likely with high dose individual supplements rather the lower levels of the same nutrients found in a multivitamin.

Is An Effect Of Supplement Use On Chemotherapy Plausible?

As a biochemist, the next question I ask is whether there is a plausible mechanism for an effect of any of these supplements on chemotherapy outcomes.

For two of the drugs in the regimen (paclitaxel and cyclophosphamide), free radical formation may contribute to their effectiveness, but it is not their main mechanism of action. Thus, it is plausible that high dose antioxidant supplements could make these drugs less effective, but the effect should be relatively small.

Tumors require high amounts of iron for proliferation, so it is plausible that excess iron could make tumors more resistant to chemotherapy. However, for premenopausal women, multivitamins with iron did not interfere with the drugs used in this study. Thus, it appears likely that RDA levels of iron, where appropriate, do not interfere with chemotherapy.

The authors said that the reason for the observed effects of vitamin B12 on chemotherapy in their study “remains to be understood”. However, the answer might be found in the dosage of vitamin B12. A previous study reported that doses of vitamin B12 that were greater than 20 times the RDA increased the risk of lung cancer.

If people in this study were taking doses of vitamin B12 in excess of 20 times the RDA, it would provide a plausible explanation for B12 interfering with chemotherapy. If not, there is no known explanation. In any case, I do not recommend taking such high doses of any supplement.

Should You Avoid Supplement Use During Chemotherapy?

Now, let’s get back to the original question: “Should you avoid supplement use during chemotherapy?” If you read the headlines saying, “Supplement Use During Chemotherapy May Be Risky”, you might think that the answer is an unqualified yes. That is also what your doctor is likely to think.

However, when you analyze the study behind the headlines you realize that the evidence supporting the headlines is very weak.

So, that puts us back to where we were before the study was published. Simply put:

It is theoretically possible that supplements interfere with chemotherapy, but we don’t know for sure.

A pragmatic approach is to avoid supplementation for a day or two before to a day or two after each round of chemotherapy. This is a strategy designed to minimize the possibility that supplementation would interfere with chemotherapy and maximize the possibility that supplementation might aid in recovery between rounds of chemotherapy.

Note: This is generic advice. I am not a medical doctor, so it would be unethical for me to provide individualized advice on how to minimize interactions between supplements and chemotherapy. What I recommend is that you ask your doctor whether my generic recommendations make sense for your cancer and your drug regimen.

If this study advanced our knowledge at all, it would be that:

The supplements most likely to interfere with chemotherapy appear to be high dose antioxidants, vitamin B12, and iron supplements.

Multivitamins, even multivitamins with iron when appropriate, are unlikely to interfere with chemotherapy.

The Bottom Line

Recent headlines have warned, “Supplement Use During Chemotherapy May Be Risky”. Is that true?

However, when you analyze the study behind the headlines you realize that the evidence supporting the headlines is very weak.

So, that puts us back to where we were before the study was published. Simply put:

It is theoretically possible that supplements interfere with chemotherapy, but we don’t know for sure.

A pragmatic approach is to avoid supplementation for a day or two before to a day or two after each round of chemotherapy. This is a strategy designed to minimize the possibility that supplementation would interfere with chemotherapy and maximize the possibility that supplementation might aid in recovery between rounds of chemotherapy.

Note: This is generic advice. I am not a medical doctor, so it would be unethical for me to provide individualized advice on how to minimize interactions between supplements and the chemotherapy drugs you are on. What I recommend is that you ask your doctor whether my generic recommendations make sense for your cancer and your drug regimen.

If this study advanced our knowledge at all, it would be that:

The supplements most likely to interfere with chemotherapy appear to be high dose antioxidants, vitamin B12, and iron supplements.

Multivitamins, even multivitamins with iron when appropriate, are unlikely to interfere with chemotherapy.

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.

How Much DHA Is Needed To Prevent Alzheimer’s

September 8, 2020 by Dr. Steve Chaney

What Are We Missing?

We are an aging population. As such, issues like cognitive decline, dementia, and Alzheimer’s Disease are of increasing concern. After all, what is the good of reaching your “Golden Years” with a healthy body if you lose your mind?

The ability of the omega-3 fatty acids DHA and EPA to reduce the risk of cognitive decline, dementia, and Alzheimer’s Disease is controversial. Some studies say yes. Others say no.

When studies are conflicting most experts simply conclude the treatment is unproven. I am sympathetic to that viewpoint, but I first like to ask the questions: “Why are the studies conflicting? What are we missing?”

I start by evaluating the strengths and weaknesses of the individual studies.

If the studies claiming the treatment works are weak, I am content to “join the chorus” and consider the treatment unproven.

If the studies claiming the treatment doesn’t work are weak, I am a strong advocate for more well-designed studies before we conclude that the treatment doesn’t work.

If both the “pro” and “con” studies are strong, I want to ask, “What are we missing?”

This is the situation with studies asking whether DHA reduces the risk of Alzheimer’s Disease and other forms of cognitive decline as we age.

Association studies show that greater intake and higher blood levels of the omega-3 fatty acids EPA and DHA are associated with lower risk of Alzheimer’s Disease.

However, most placebo-controlled clinical trials with either DHA alone or DHA + EPA have come up negative. Of course, one can always argue that most of the placebo-controlled clinical trials were too short or too small to show a statistically significant effect. But, my question remains, “What else are we missing?”

One recent study has provided an interesting clue. The authors of the study postulated that B vitamins were required to deliver omega-3 fatty acids to the brain, and their study showed that omega-3 fatty acids were only effective at decreasing the risk of cognitive decline in subjects who also had optimal B vitamin status.

In other words, this study suggested that studies on the effect of omega-3 supplementation and risk of developing Alzheimer’s are doomed to failure if a significant percentage of the subjects have sub-optimal B vitamin status.

The authors of the current study ( IC Arellanes et al, EBioMedicine, doi.org/10.1016/j.ebiom.2020.102883) proposed two additional hypotheses for the negative results of previous clinical trials and designed an experiment to test their hypotheses. Their hypotheses were:

Uptake of DHA and EPA by the brain is very inefficient, and previous studies have not used sufficient doses of DHA or DHA plus EPA to see a significant effect on cognitive impairment.

The APOE4 gene further decreases the uptake of DHA and EPA by the brain.

Before I describe how the study was done, I should probably provide some context by describing how DHA and EPA reach the brain and the role of the apoE protein in the process. It’s time for my favorite topic: “Biochemistry 101”.

Biochemistry 101: What Does The ApoE Protein Do?

If you have ever tried to mix oil and water, it should come as no surprise to you that fats, including DHA and EPA, and cholesterol are not water soluble. That leaves our bodies with a dilemma. How do they get the fat and cholesterol we eat to pass through our bloodstream and get to our cells, where they are needed?

Our body’s solution is to incorporate the fat and cholesterol into particles called lipoproteins. Lipoprotein particles sequester the fat and cholesterol in their interior and surround them with water soluble phospholipids and proteins. Lipoproteins allow our bodies to transport fat and cholesterol through our bloodstream to the tissues that need them.

The next question, of course, is how the lipoproteins know which cells need the fat and cholesterol. This is where apoproteins like apoE come into play. We can think of the apoE protein as a zip code that directs lipoproteins to cells with an apoE receptor.

Our nervous system contains lots of apoE receptors, and binding of the apoE protein to its receptor is instrumental in the delivery of DHA, EPA, and cholesterol to our nervous system.

DHA and cholesterol are both important for brain health. That is because they are major components of the myelin sheath that wraps around our neurons and protects them. EPA may also be important for brain health because its anti-inflammatory effects are thought to prevent the accumulation of the amyloid plaques that are the hallmark of late-onset Alzheimer’s Disease.

There are three major versions of the APOE gene, APOE2, APOE3, and APOE4. Each of them plays slightly different roles in our body. However, it is the APOE4 version that is of interest to us. About 25% of us have the APOE4 version of the APOE gene and it increases our risk of developing Alzheimer’s Disease by a factor of two.

We do not know why this is, but one hypothesis is that lipoproteins with the apoE4 protein have more difficultly delivering much needed DHA, EPA, and cholesterol to the brain. This is one of the hypotheses that the authors set out to study.

How Was The Study Done?

There are two things you should know about this study.

This was a pilot study designed to test the author’s hypotheses and allow them to choose the correct dose of DHA to use for a subsequent study designed to test whether high-dose DHA can reduce the risk of developing Alzheimer’s Disease.

This was a very small study. That’s because the only way to determine how much DHA and EPA reaches the nervous tissue is to perform a lumbar puncture and obtain cerebrospinal fluid at baseline and again at the end of the study. Lumbar punctures are both painful and a bit risky. They were lucky to find 26 individuals who consented to the lumbar punctures.

This was a double-blind, placebo controlled clinical study.

Half the subjects were given 2,152 mg/day of DHA for 6 months, and half were given a daily placebo consisting of corn and soybean oil for 6 months.

Because previous studies have suggested that B vitamins were important for DHA and EPA uptake by nervous tissue, all subjects received a B vitamin supplement.

Levels of DHA and EPA were measured in both plasma and cerebrospinal fluid at baseline and again at the end of 6 months. Note: The subjects were only supplemented with DHA. The investigators were relying on the body’s ability to convert DHA into EPA.

All subjects were screened for APOE4

Other important characteristics of the study subjects were:

Average age was 69. They were 80% female.

All of them had a close family member who had previously been diagnosed with dementia, but none of them had been diagnosed with cognitive impairment at the time of entry into the study.

Around 45% of them had the APOE4 version of the APOE.

In other words, none of them currently had dementia, but most were at high risk of developing dementia.

How Much DHA Is Needed To Prevent Alzheimer’s?

After 6 months of supplementing with over 2,000 mg/day of DHA:

DHA levels in the blood had increased by 200%.

However, DHA levels in cerebrospinal fluid had increased by only 28%.

Moreover, DHA levels in cerebrospinal fluid were 40% lower in subjects who had the APOE4 gene compared to subjects with the APOE2 and APOE3

EPA levels in cerebrospinal fluid averaged about 15-fold lower than DHA levels. When they looked at the effect of DHA supplementation on EPA levels.

EPA levels in plasma had increased by 50%.

EPA levels in cerebrospinal fluid had increased by 43%.

EPA levels in cerebrospinal fluid were 3-fold lower in subjects who had the APOE4 gene compared to subjects with the APOE2 and APOE3

The authors concluded:

“We observed only a modest (28%) increase in cerebrospinal fluid DHA levels with 2152 mg per day of DHA supplementation. This finding has implications for past clinical trials that have used lower doses (e.g. 1 g daily of DHA supplements or less) and were overwhelmingly negative. Using lower doses of omega-3 supplements may have resulted in limited omega-3 brain delivery.”

“Another aspect affecting the response to DHA supplementation is APOE4 status. Subjects with the APOE4 gene showed lower DHA levels and significantly lower EPA levels than subjects with other APOE genes”.

“In summary, our study suggests that higher doses of omega-3 fatty acids (2 or more g of DHA) are needed to ensure adequate brain delivery, particularly in APOE4 carriers…Past low dose (1 g per day or less) omega-3 supplementation trials in dementia prevention may not have provided adequate brain levels to fully evaluate the efficacy of omega-3 supplementation on cognitive outcomes.”

Based on the results from this study the authors are currently testing the effect of B vitamins and high dose DHA supplementation on cerebrospinal fluid fatty acid levels, brain imaging, and cognitive outcomes in a larger ongoing clinical trial.

What Does This Study Mean For You?

The ability of the omega-3 fatty acids DHA and EPA to reduce the risk of cognitive decline, dementia, and Alzheimer’s Disease is confusing. Studies disagree.

In situations like this, most experts dismiss the hypothesis as “unproven”. However, I like to ask, “What are we missing?”

One recent study provided a clue. It suggested that omega-3s and B vitamins were interdependent. We need both to reduce cognitive decline. However, that might not be the complete answer.

This study gave both DHA and B vitamins to subjects and discovered another interesting clue. The study suggests we may not have been giving subjects enough omega-3s to see a significant effect on cognitive decline.

Let me start by saying this study did not test whether or not DHA supplementation prevents cognitive decline, dementia, and Alzheimer’s Disease. Nor does it tell us how much DHA is needed to prevent Alzheimer’s Disease, other than to show that anything less than 2 g per day is likely to be inadequate.

However, the study did make two important advances:

#1: It showed just how difficult it is to deliver adequate amounts of DHA and EPA to the brain. This is important because it shows:

Most previous studies have not used high enough doses of DHA or DHA plus EPA to evaluate the effect of omega-3 fatty acids on cognitive decline. Those studies were not simply negative. They were doomed to failure. The studies were worthless.

That means we should stop saying that the ability of omega-3s to prevent cognitive decline and diseases like Alzheimer’s is unproven. Instead, we should say that hypothesis has not adequately been tested.

That also means future studies of the ability of DHA to reduce the risk of cognitive decline, dementia, and/or Alzheimer’s will need to use much higher doses or a better delivery system to get adequate amounts of DHA and EPA into the brain.

#2: It showed that the APOE4 gene significantly decreases the ability of the brain to accumulate DHA and EPA. This has several important implications.

Because both DHA and EPA are vital for brain health, this may explain why the APOE4 gene increases the risk of Alzheimer’s Disease.

It also means those at highest risk for Alzheimer’s Disease are the ones who are most likely to have difficulties accumulating DHA and EPA in their brain.

Once again, it means future studies of the ability of supplemental DHA to reduce the risk of Alzheimer’s Disease will need to use much higher doses of DHA.

The Bottom Line

The ability of the omega-3 fatty acids DHA and EPA to reduce the risk of cognitive decline, dementia, and Alzheimer’s Disease is controversial.

Association studies show that greater intake and higher blood levels of the omega-3 fatty acids EPA and DHA are associated with lower risk of Alzheimer’s Disease.

However, most placebo-controlled clinical trials with either DHA alone or DHA + EPA have come up negative.

In situations like this, most experts dismiss the hypothesis as “unproven”. However, I like to ask, “What are we missing?”

One recent study provided a clue. It suggested that omega-3s and B vitamins were interdependent. We need optimal amounts of both to reduce dementia. However, that might not be the complete answer.

This study gave both DHA and B vitamins to participants and discovered another interesting clue. The study suggests we may not have been giving subjects enough omega-3s to see a significant effect on cognitive decline.

The authors of the study hypothesized:

Uptake of DHA and EPA by the brain is very inefficient, and previous studies have not used sufficient doses of DHA or DHA plus EPA to see a significant effect on cognitive impairment.

The APOE4 gene, which is known to increase the risk of Alzheimer’s Disease, further decreases the uptake of DHA and EPA by the brain.

Their study confirmed their hypotheses and made two important advancements:

#1: It showed just how difficult it is to deliver adequate amounts of DHA and EPA to the brain. This is important because it shows:

Most previous studies have not used high enough doses of DHA or DHA plus EPA to evaluate the effect of omega-3 fatty acids on cognitive decline. Those studies were not simply negative. They were doomed to failure. The studies were worthless.

That means we should stop saying that the ability of omega-3s to prevent cognitive decline and diseases like Alzheimer’s is unproven. Instead, we should say that hypothesis has not adequately been tested.

That also means future studies of the ability of DHA to reduce the risk of cognitive decline, dementia, and/or Alzheimer’s will need to use much higher doses or a better delivery system to get adequate amounts of DHA and EPA into the brain.

#2: It showed that the APOE4 gene significantly decreases the ability of the brain to accumulate DHA and EPA. This has several important implications.

Because both DHA and EPA are vital for brain health, this may explain why the APOE4 gene increases the risk of Alzheimer’s Disease.

It also means those at highest risk for Alzheimer’s Disease are the ones who are most likely to have difficulties accumulating DHA and EPA in their brain.

Once again, it means future studies of the ability of supplemental DHA to reduce the risk of Alzheimer’s Disease will need to use much higher doses of DHA.

Based on the results from this study the authors are currently testing the effect of B vitamins and high dose DHA supplementation on DHA and EPA levels in the brain, brain imaging, and cognitive outcomes in a larger ongoing clinical trial.

For more details, read the article above. For a better understanding of the roles of DHA, EPA, and the APOE gene in brain health, you may want to read my “Biochemistry 101” section 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.