Category Archives: Supplements

Study: Multiple Dietary Supplements Do Not Improve Measures Of Health

DietarySupplements6A small study (56 men and women, 38-55 years old) found that taking supplements for 6 months had no effect on a number of cardiovascular risk factors:

Multiple Dietary Supplements Do Not Affect Metabolic And Cardio-Vascular Health, Aging, September 2013

Both the supplement group and the control group took a daily multivitamin/mineral. But the supplement group also took the following supplements each day (“the most self-prescribed dietary supplements in middle-aged men and women eating a Western diet”):

100 mg resveratrol ($72 for 180 days)
800 mg green tea extract ($115)
800 mg black tea extract ($240)
800 mg white tea extract ($141)
250 mg pomegranate extract ($156)
650 mg quercetin ($180)
500 mg acetyl-l-carnitine ($68)
600 mg lipoic acid ($318)
900 mg curcumin ($117)
1 g sesamin ($62)
1.7 g cinnamon bark extract ($230)
1.0 g fish oil ($70)

Those costs in parentheses: I went online and priced each supplement at the given strength.  I chose brands randomly but looked for no other ingredients and an easily scalable potency.  Total cost for 6 months (not counting the vitamin/mineral supplement): $1769.

After 6 months, there was no effect on:

Arterial stiffness
Endothelial (blood vessel) function
Body weight
Body fat (measured by DEXA)
Blood pressure
Plasma lipids (triglycerides, total cholesterol, LDL, HDL)
Glucose (fasting)
Insulin (fasting)
Insulin resistance (HOMA-IR)
Advanced glycation end-product (AGE) concentrations
Biomarkers of inflammation and oxidative stress

Conclusion: “In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals.”


“Since completing the randomized trial, all but one of the participants in the SUP group continued for another 6 months on the supplementation regimen. Even with this longer, 12 month period of supplementation, no changes in any outcome were observed.”

Even the authors were surprised at the lack of effect:

“Because all the supplements that we used have been reported to have powerful anti-inflammatory and anti-oxidant effects, it is interesting that no biological change in endothelial function was observed.

One possible explanation for the lack of beneficial metabolic effects of these over-the counter dietary supplements could be the low phytochemical bioavailability or inadequate supplement potency of the phytochemicals contained in some of these compounds which are available without prescription [32]. Nonetheless, the fact remains that millions of individuals in USA and Europe are consuming these supplements, sometimes instead of a healthy diet and conventional medical treatment, which might contain hazard trace amounts of pesticides and heavy metals, including lead, arsenic, mercury, and cadmium [1,33]”

The good news was that there was no negative effect, at least on the markers tested, except for gastrointestinal distress from taking so many supplements. The bad news was that these supplements didn’t do anything, but, as you can see, cost about $1769 for a 6-month supply!

These are the kinds of controlled, efficacy studies supplement makers don’t want to perform, don’t perform, and don’t have to perform. (From FDA: “Unlike drug products that must be proven safe and effective for their intended use before marketing, there are no provisions in the law for FDA to “approve” dietary supplements for safety or effectiveness before they reach the consumer.”) Supplement makers enjoy helping to separate consumers from their disposable income without much justification other than cell culture or animal studies and a few testimonials (which could be placebo effect, which is why you conduct studies, to rule out placebo effect).

Calcium Supplements Found (Again) To Increase Risk For Heart Attack, Stroke

I’m reposting this from April 2011 because I know so many people, women especially, who insist on taking calcium supplements.
The leading cause of death for women in America is heart disease.1 It now looks like some of those heart attacks (and strokes) may have been provoked by the calcium supplements women were taking to protect their bones. (Heart disease is the leading cause of death in men too, but I don’t think men are pressured as much as women to take calcium. Men may also be refraining because of the spectacular association between calcium and prostate cancer.)

A revisit of data in the huge Women’s Health Initiative (WHI) study found that women who took calcium supplements increased their risk for heart attack and stroke:

Calcium Supplements With Or Without Vitamin D And Risk Of Cardiovascular Events: Reanalysis Of The Women’s Health Initiative Limited Access Dataset And Meta-Analysis, British Medical Journal, April 2011

The original WHI analysis showed no such risk. But that was because thousands of women who were already taking calcium before the study weren’t told to stop. If those calcium-takers ended up in the placebo group (which was supposed to receive no calcium), you might expect them to show similar heart attack risk as intervention groups (which did receive calcium). That’s exactly what they found.

This new analysis looked at women who weren’t taking calcium before the study. If those women were randomized to a group that received calcium, it did indeed increase their risk for heart attack and stroke.

The Amount Of Calcium Didn’t Matter

Here’s Dr. Ian Reid, senior author of the new analysis:

It is actually taking a supplement that matters, not how much of it you take, that causes this increase in heart risk.”

And from a HeartWire interview:

“That makes sense, [Reid] says, since even small levels of supplemental calcium create “abrupt” increases in blood calcium levels within hours. This speaks to one criticism levied at the group’s earlier work — namely, that the cardiovascular events seemed to be occurring too swiftly to be related to calcified plaques.

MI spikes likely reflect a more acute response to blood calcium levels, including changes in platelet function, blood coaguability, or endothelial cell activity.”

Calcium Supplements And Cardiovascular Events: New Data, More Debate, HeartWire, April 19, 2011

I would like to add to those mechanisms something readers of this blog already know – calcium lowers vitamin D levels, and vitamin D is thought to be cardio-protective:

“If serum levels of calcium are high, production of 1, 25 D is suppressed by reduced parathyroid hormone production.”

Dairy Products, Calcium, and Vitamin D and Risk of Prostate Cancer, Epidemiologic Reviews, 2001

The present analysis found no benefit in taking vitamin D.

Dr. Reid: “Our own recommendation is to critically review the use of calcium supplements, since the data in this paper suggests that they do more harm than good.”

Women Taking Calcium Supplements May Risk Heart Health, Researchers Say, HealthDay, April 19, 2011

1 CDC: Leading Causes of Death in Females, 2010

Less Than 1 Percent Of Dietary Supplements Are USP-Verified

USP just backed up Dr. Offit’s claim that a mere pittance of dietary supplements are USP-verified. Hardly any meet standards set by the U.S. Pharmacopeia for ensuring that what is on a supplement’s label is what is in the bottle:


USP ensures ensure the strength, quality, purity, and believe it or not, the identity of a product. You would think that a bottle of, say, St. John’s wort contains St. John’s wort, but:

“One bottle of St. John’s wort was wholly made of ground rice, while another contained a known laxative called Alexandrian senna. Neither of the 2 bottles tested contained the common active ingredient in St. John’s wort.”

I guess companies really can get away with selling cheap fillers in lieu of active ingredients.

USP Verified Label – Look For It When You Buy Supplements

Before reading the rest of this post, go to your vitamins and supplements and look for this label (just the letters “USP” don’t count, you have to see this exact mark):

For example:

The United States Pharmacopeia (USP) is a private, nonprofit organization that publishes the official pharmacopeia for drugs (both prescription and over-the-counter), food additives, and dietary supplements. A pharmacopeia is a document that describes what’s in or how to make a drug.

The USP, which came into being in 1820, predated the Food and Drug Administration (FDA) by 86 years. To this day, FDA continues to depend on, and enforce, USP standards. Those standards ensure products are of the correct identity, strength, quality, purity, and consistency. The buck stops with the USP when it comes to identifying a drug.

Prescription drugs are required to meet USP standards, dietary supplements are not. (USP, White Paper, Access To Good Quality Dietary Supplements, September 2009.) Two other bits of data from that White Paper:

“Manufacturers set their own limits for contaminants such as heavy metals, microbial limits, fungal toxins, or pesticides.”

“Under the current law and regulations, there is no way of knowing the quality standards to which each product is held, and thus, there is no way to determine whether two products with the same dietary supplement ingredients are the same or different.”

That is why the 30 top-selling fish oil supplements all contain mercury, some at levels above the maximum set by the EPA for drinking water.  Manufacturers can set their own limits.

Fortunately, the USP conducts a verification program for dietary supplements. Unfortunately, the program is voluntary and not widely used by the supplement industry:

[USP] awards the use of a distinctive USP Verified Mark for dietary supplements to products that meet the program’s rigorous standards. The distinctive USP Verified Mark on a dietary supplement product is intended to assure consumers, healthcare practitioners, and pharmacists that the product:

  • Contains the ingredients stated on the label in the declared amount and strength
  • Is within limits for contaminants such as heavy metals, pesticides, and microbes
  • Will disintegrate or dissolve as per USP’s requirements, where applicable, to release nutrients for absorption into the body
  • Has been manufactured using well-documented and controlled procedures in accordance with Good Manufacturing Practices (GMPs)

Back to that task at the top of this post … Did you find the USP Verified mark? I’ll bet you didn’t. According to Dr. Paul Offit, chief of Infectious Diseases at CHOP (Children’s Hospital of Philadelphia, which just, controversially, removed almost all dietary supplements from its list of approved medications) only “0.001 percent” of supplements are USP-verified. That means your supplements may not contain what the label says they contain (i.e. do not meet USP standards for identity, strength, quality, and purity).  If they did, why wouldn’t the manufacturer seek to obtain use of the mark?

I can’t believe that a wholesale club like BJ’s has an inexpensive house brand (Berkley&Jensen) that includes USP verified products but a high end supplement like Twinlab does not (even though they refer to “USP” on their labels).  See List of USP Certified Dietary Supplements.

Nature Made is on the USP-verified list:


From Wikipedia: “Products that meet the requirements of the program can display the USP Verified Dietary Supplement Mark on their labels. This is different from seeing the letters “USP” alone on a dietary supplement label, which means that the manufacturer is claiming to adhere to USP standards. USP does not test such products as it does with USP Verified products.”

By the way, USP requires:

“Care shall be taken not to state or imply that the USP Verified Mark indicates that USP endorses the safety or efficacy of the product.”

USP ensures the identity, strength, quality, and purity of a drug, but it doesn’t ensure safety, and it makes no comment about whether a supplement does what it says it can do. That falls under FDA, but there’s no pre-market enforcement as there is with prescription drugs.

We demand fresh, organic, locally-grown, minimally processed, uncontaminated food, but we toss those standards to the wind when it comes to supplements – opting for stale, non-organic (pesticides), genetically modified, imported, ultra-processed pills with no assurance of potency, purity, efficacy or safety.

See also:
US Dietary Supplement Verification Program (pdf)

USP Verified Dietary Supplements, USP Resource Page

Antioxidants Including Vitamin E Found To Promote Lung Cancer

VitaminE8Reuters is reporting on a new study that investigated whether antioxidants could fight cancer. Not only did antioxidants not help slow cancer growth, but…

“The antioxidants caused a 2.8-fold increase in lung tumors, made the tumors more invasive and aggressive, and caused the mice to die twice as quickly – all compared to mice not given antioxidants.

When the antioxidants were added to human lung tumor cells in lab dishes, they also accelerated cancer growth.”

Here’s the mechanism:

“What seems to happen is that antioxidants indeed decrease DNA damage, as expected. But the damage becomes so insignificant as to be undetectable by the cell. The cell therefore does not deploy its cancer-defense system.”

The scientists stressed that the results do not pertain to foods such as fruits and vegetables that are naturally high in antioxidants.”

Antioxidants Including Vitamin E Can Promote Lung Cancer: Study, Reuters, 29 January 2014

Co-author of the study, Per Lindahl, said “antioxidants allow cancer cells to escape cells’ own defense system,” letting existing tumors, even those too small to be detected, proliferate uncontrollably.

Here’s the study:

Antioxidants Accelerate Lung Cancer Progression in Mice, Science Translational Medicine, 29 January 2014

“Antioxidants are widely used to protect cells from damage induced by reactive oxygen species (ROS). The concept that antioxidants can help fight cancer is deeply rooted in the general population, promoted by the food supplement industry, and supported by some scientific studies.

We show that supplementing the diet with the antioxidants N-acetylcysteine (NAC) and vitamin E markedly increases tumor progression and reduces survival in mouse models of B-RAF– and K-RAS–induced lung cancer. RNA sequencing revealed that NAC and vitamin E, which are structurally unrelated, produce highly coordinated changes in tumor transcriptome profiles, dominated by reduced expression of endogenous antioxidant genes. NAC and vitamin E increase tumor cell proliferation by reducing ROS, DNA damage, and p53 expression in mouse and human lung tumor cells. Inactivation of p53 increases tumor growth to a similar degree as antioxidants and abolishes the antioxidant effect.

Thus, antioxidants accelerate tumor growth by disrupting the ROS-p53 axis. Because somatic mutations in p53 occur late in tumor progression, antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations such as smokers and patients with chronic obstructive pulmonary disease who receive NAC to relieve mucus production.”

As it stands, smokers are being advised to get more antioxidants, e.g. “Individuals who smoke require 35 mg/day more vitamin C than nonsmokers.” Hm. Best to eat an orange and skip the supplement.

Dr. Campbell described this, in a conceptual way, in his book, “Whole.” When you put a chemical – in isolated, concentrated form – into the chemical soup that is our body, you can’t easily predict how all the other chemicals are going to respond.

Dr. Paul Marantz, epidemiologist at Albert Einstein College of Medicine:

“It’s disappointing but not surprising that people’s beliefs are not modified by scientific evidence. … People so want to believe there is a magic bullet out there.”

30 Best-Selling Fish Oil Supplements – All Contain Mercury


Every fish oil supplement that LabDoor tested, including the ones you see here, contained measurable amounts of mercury. Three products contained 50% or greater of the allowable methylmercury content per serving.

A fairly new (2012) company, LabDoor, is taking on the poorly regulated supplement industry. They’re testing products for contaminants and label claims. Here’s their run-down of the 30 best-selling fish oil supplements in the US:

LabDoor: Top 30 Fish Oil Supplements

People believe labels. If one bottle says it contains 200 mg of something, and another says 300 mg, you would think the one with the higher stated dose would indeed contain more, and would justify the higher price. Not true. At least not all of the time.  Since no one is regularly checking that what is on a supplement’s label is what is in the bottle, manufacturers are lax in quality control.

LabDoor found:

  • Total omega-3 content ranged from -60.0% to +62.5% versus their stated label claims.
  • 21/30 products demonstrated omega-3 levels that varied by over 10% off their label claims, 15 of which recorded a 25% variance between actual versus claimed content.
  • EPA + DHA content showed significant ingredient variance, ranging from -50.7% to +90.2% versus its stated label claims.

-60%. So, you buy one of these fish oil supplements, it says it contains 500 mg, but it only contains 200 mg. You paid for 500 mg too.
+90.2%. Too much omega-3 increases the risk for bleeding and stroke. And you don’t know how much you’re taking when the label is wrong.

They looked at mercury.  For relativity’s sake, the EPA has set a maximum contaminant level for mercury in drinking water at 2 ppb. LabDoor found:

  • Every fish oil supplement contained measurable amounts of mercury, with the category averaging 2.9 PPB (parts per billion) of mercury.
  • The worst offenders were Nature Made Cod Liver Oil and Natrol’s Omega-3, which both recorded mercury levels of 6 PPB.

As to organic mercury, or methylmercury, which is more toxic to the body than inorganic mercury, LabDoor found:

  • Every product contained measurable amounts of methylmercury, with 3 products recording 50% or greater of the allowable methylmercury content per serving.

As to freshness:

  • All products recorded measurable levels of oxidation; the category averaged a TOTOX score of 21.3 (Upper Limit = 26). The majority of products measured scores above 20.
  • 12/30 products recorded peroxide levels (measure of primary oxidation) at or above the upper limit.

Other findings:

  • Current clinical research indicates that DHA intake should exceed that of EPA, with the recommended ratio of 3:2. The fish oil supplements in this study trended in the opposite direction, containing nearly twice as much EPA as DHA.
  • Eight supplements in this study contained ‘natural’ flavors such as citrus-derived additives. One product, Coromega Omega-3, also contained benzoic acid, a popular antibacterial agent linked to carcinogenic risks when combined with vitamin C.

There you have it. The top 30 fish oil supplements all contain mercury, some at dangerously high levels; are likely to contain either less or more omega-3 than is stated on the label, could be contaminated with undesirable, possibly harmful, flavors, fillers, or preservatives; and have oxidized so much they’ll most certainly result in fish-burp.

Americans spent $1.1 billion on fish oil supplements in 2011.

Low Vitamin D Not A Cause Of Poor Health, More Likely A Result

Population studies describe an association between levels of vitamin D and disease … low vitamin D seems to increase risk for heart disease, diabetes, some cancers, and other chronic illnesses. But does it? Supplementation with vitamin D, in intervention studies, does not improve health. What’s going on? Autier et al. in this recent analysis say that low vitamin D may merely be a marker for ill health:

Vitamin D Status And Ill Health: A Systematic Review, The Lancet Diabetes and Endocrinology, Online 6 December 2013

“We did a systematic search of prospective and intervention studies that assessed the effect of 25(OH)D concentrations on non-skeletal health outcomes in individuals aged 18 years or older. We identified 290 prospective cohort studies (279 on disease occurrence or mortality, and 11 on cancer characteristics or survival), and 172 randomised trials of major health outcomes and of physiological parameters related to disease risk or inflammatory status.

Investigators of most prospective studies reported moderate to strong inverse associations between 25(OH)D concentrations and cardiovascular diseases, serum lipid concentrations, inflammation, glucose metabolism disorders, weight gain, infectious diseases, multiple sclerosis, mood disorders, declining cognitive function, impaired physical functioning, and all-cause mortality. High 25(OH)D concentrations were not associated with a lower risk of cancer, except colorectal cancer.

Results from intervention studies did not show an effect of vitamin D supplementation on disease occurrence, including colorectal cancer. In 34 intervention studies including 2805 individuals with mean 25(OH)D concentration lower than 50 nmol/L at baseline supplementation with 50 μg* per day or more did not show better results. Supplementation in elderly people (mainly women) with 20 μg vitamin D per day seemed to slightly reduce all-cause mortality.

The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status is reported in a wide range of disorders.”

* 50 μg is 50 micrograms or about 2000 IUs

Vitamin D has become a darling in the supplement world. That reputation may not be founded. What’s more likely is that low vitamin D levels, rather than being a cause of poor health, are a consequence.

Lead author of the study, Dr. Autier:1

“Ageing and inflammatory processes involved in disease occurrence… reduce vitamin D concentrations, which would explain why vitamin D deficiency is reported in a wide range of disorders.”

1 Doubt Cast On Vitamin D’s Role Against Disease, BBC, 5 December 2013

Talking To Your Doctor About Supplements

Here’s an excerpt of Steve Mister’s* letter to the editor about “Skip the Supplements” (by Paul A. Offit and Sarah Erush, New York Times, December 15):

“People today want to be part of the decision-making process when it comes to their health. When consumers believe that their physicians won’t have that informed dialogue, it drives them to be less candid about their supplement use. That would be an unfortunate result for everyone.”

I don’t agree with many of Mister’s claims. Here’s one: “Multivitamins are an excellent source of nutrients to fill in the gaps we miss in our less-than-perfect diets.”

And Mister saying it:

Pills don’t fill gaps, our body fills gaps. It does so by, for instance, increasing absorption and decreasing elimination.

But I agree with that statement he made above, “When consumers believe that their physicians won’t have that informed dialogue, it drives them to be less candid about their supplement use.” Healthcare professionals should be educated on the risks and benefits of supplements, and be willing to engage in a dialog, a non-judgmental conversation. Has that been your experience?

* Mister is president of the Council for Responsible Nutrition, the trade association for the dietary supplement industry.