Nutritional Supplementation and JAMA
In the last few months there has been a disappointing series of nutritional studies published in the Journal of the American Medical Association. JAMA was rabidly opposed to supplementation until 2002, when they published an excellent article that proposed that taking supplements could reduce the risk of chronic disease.  That article was right on the money. This recent group of articles challenges those findings, but you will soon find that they were all seriously flawed. Let’s review these clinical trials, and consider how asking the wrong question can yield the wrong answers, and how that process generates negative bias against supplementation.
The first study we will discuss is the:
Physicians’ Health Study II
The first 2 JAMA papers we will review [2, 3] involve the results from the Physicians’ Health Study trial (PHS II). Researchers studied 14,641 male physicians in the United States, aged 50 years or older. They divided them into 4 groups, and gave most of them a placebo, while only 3,656 received both the 400 IU of vitamin E every other day and 500 mg of vitamin C daily. They tracked this group for 8 years.
This trial generated 2 separate articles:
The Heart Disease Report
The first paper  concluded that vitamin C and E supplementation did not reduce the risk of major cardiovascular events. However, their selection of candidates was very seriously flawed:
• The median age of participants was 64.3 years old 
• 42% already had pre-existing high blood pressure
• 6% already had pre-existing heart disease
• 6% already had pre-existing diabetes
The Cancer Report
The second paper  used this same flawed cohort to maintain that vitamin C and E supplementation also did not reduce the risk of prostate, or other forms of cancer. The weak points in this study include:
• 9% already had pre-existing cancers
• 44% were past or current smokers
• All of them were given synthetic supplements
It’s embarrassing to see how much money and time was wasted on such a flawed study design. Why study 64 year olds, many of whom already have the disease under review? Why give them synthetic vitamins? Why give them Vitamin E every other day? The most this study should conclude is that if you wait until you are 64, it may be too late to hope that supplementation may reduce your health risks.
The second large trial we will review is:
Antioxidant and Folic Acid Heart Study
This study was actually one of five “legs” of a much larger clinical trial called the Women’s Health Initiative. The overall study was designed to see whether hormone replacement therapy (HMT), antioxidants, or B vitamins could reduce heart disease or cancer incidence. You may recall that the hormone trial was discontinued in 2002 when it was revealed that HMT had actually increased breast cancer rates by 26%, and heart attack rates by 29%. 
Like the PHS II study, this trial led to the publication of 2 different papers [4, 5]. In this trial, researchers gave folic acid, vitamin B6, and vitamin B12 to 5442 female health professionals, aged 42 years or older, over a 7-year period. Interestingly, the group receiving the B vitamins lowered their homocysteine levels by 18%, compared with the placebo group.
The Heart Disease Report
The first published paper reported that taking the 3 B vitamins did not reduce the risk of major cardiovascular events.  Although the JAMA paper makes that conclusion, the principal author, Dr. Marian Neuhouser made a rather different statement in a Medscape interview recently , when she said that there was “a slightly decreased risk for heart attack (MI) in those who took stress multivitamins — the ones that have high doses of B vitamins, vitamin C, zinc, and selenium — but because there were so few cases in this group, and because there were only 64 MIs among all these women, it’s a little bit hard to draw a firm conclusion, so we didn’t want to draw particular attention to this.” Unfortunately, the rest of the participants only received 3 of the eight B vitamins.
The problems with this trial were:
• The median age of participants was 64 years old 
• All the participants selected were “high risk”, already having pre-existing cardiovascular disease (CVD) or at least 3 or more major risk factors for CVD. If you were healthy, you could not participate in this trial.
The Cancer Report
The second paper  used the same flawed cohort to do a statistical analysis for cancer incidence. The weak points in this study include:
• No statistics were reported for pre-existing cancers
• This paper does not mention the other “leg” that received antioxidants, or the sub-group who took the “stress vitamins” mentioned in the Medscape interview. 
Again, we are being told that supplements do not prevent heart disease or cancer, when in fact, what they actually explored was the response of older, sick individuals to taking 3 of the eight B vitamins. That’s like using a “stacked deck” to prove you can’t win at cards. I refer to this fallacious thinking as the search for:
The “Silver Bullet”
The major fault in all these reports is that they treat isolated nutrients as though they were experimental drugs. It’s not hard to understand why this flawed approach occurs. Many of these same researchers have a background in running clinical drug trials. As an example: Big Drug Company has just developed an experimental drug to manage heart arrhythmia. To test it, they gather a “cohort” of 200-500 individuals with pre-existing heart arrhythmia, and then give half of them the new drug, and the other half receive placebo.
However, the drug-testing model does not work well with nutrients. Using people who already have heart disease, to see if B vitamins can extinguish it, is ridiculous. All the long-term trials suggest that it is the deficiencies in those vitamins that contributes to the onset of heart disease.
All the retrospective lifestyle studies of the last 40 years have shown a direct relationship between diet and disease. [11-13] The newest study, just published in the Circulation journal (2-18-09), reviewed 74,886 files from the Nurses’ Health Study, and found that the lowest incidence of heart disease and stroke was in women who’s diets most closely resembled the traditional Mediterranean diet.
That diet contains minimally processed, mostly plant-based foods, with an abundance — not just in terms of quantity, but also in terms of variety — of different plant foods and fish.
The author stated: “Compared with the typical US diet, the Mediterranean-type diet requires a shift toward a more plant-based meal, which means eating less meat and getting more of the day’s protein from plant sources, such as beans and nuts”. 
Since the discovery of penicillin by Fleming in 1928, science has succumbed to the siren call of the “silver bullet” approach to disease. A large chunk of the $29 billion budget of the National Institute of Health (the principal sponsor for American research) is devoted to funding single-substance or intervention studies. 
The Landmark Study
To date, there is only one retrospective study that has examined the health benefits of taking a full-spectrum of vitamins and minerals over a prolonged period of time. I’m referring to the Landmark Study, which was financed by the Shaklee Corporation.  The results from the study clearly demonstrate that longtime use of broad-spectrum nutrients DOES reduce the incidence of vascular disease, heart disease, diabetes, stroke, and cancer.
The primary database the authors used for health comparisons was the National Health and Nutrition Examination Survey (NHANES), a collection of millions of health questionnaires gathered since the 1970s. 
In this study, they compared a large group of Shaklee members, who had used a wide variety of supplements for 20+ years, with NHANES groups which had not supplemented, or ones who had used “at least” one multi-vitamin daily.
Lab analysis revealed that the long-term group maintained much higher blood levels of all the essential vitamins and minerals, and they also experienced reduced or normal levels of all the key biomarkers for disease.
Biomarkers refer to the standard blood tests that are used to test for and diagnose disease.
In the 3 groups studied in Landmark, only the long-term users had normal blood homocysteine levels. Homocysteine is a key indicator for vascular disease, and is closely associated with sudden-death heart attack and stroke. 
C-reactive Protein (CRP) levels are an indicator of inflammation, and high levels are associated with many disease processes, including heart disease, diabetes, and colon cancer.  Unlike the 2 control groups, the long-term group maintained completely normal physiologic levels for CRP.
High levels of triglycerides and low-levels of high-density cholesterol (HDL) are also associated with vascular disease, heart disease, and stroke.  Again, the long-term group scored completely normal cholesterol levels while the 2 other groups didn’t. They also maintained completely normal blood pressure levels!
This study offers compelling proof that long-term supplement use can reduce the incidence of the most serious causes of death and disability.  Finally, it demonstrates that there are no negative side effects to long-term supplement use. This contradicts earlier studies that suggested that beta-carotene was associated with increases in lung cancer. However, all the studies that reported those results used synthetic beta-carotene in the trial.
1. JAMA 2002 (Jun 19); 287 (23): 3127–3129
2. JAMA 2008 (Nov 12); 300 (18): 2123-2133
3. JAMA 2009 (Jan 7); 301 (1): 52-62
4. JAMA 2008 (May 7); 299 (17): 2027-2036
5. JAMA 2008 (Nov 5); 300 (17): 2012-2021
6. Arch Intern Med 2009 (Feb 9); 169 (3):
7. Medscape Family Medicine; 11-24-2008
8. Medscape Family Medicine; 12-12-2006
9. Yale/New Haven Hospital Review; 9-24-2002
10. Medscape’s Heartwire; 2-10-2009
11. National Health and Nutrition Examination Survey
12. Framingham Heart Study Website
13. The Nurses’ Health Study
14. Medscape Medical News; 2-18-2008
15. The NIH Yearly Budget
16. Nutrition Journal 2007 (Oct 24); 6 (30)
17. National Health and Nutrition Examination Survey
18. Nutrition Science News; December 2000
19. C-reactive Protein
20. Alternative Medicine Review 2001 (Dec); 6 (6): 590–600
21. “Mortality Patterns in the United States”
22. Vitamins at Kids Health
23. The FrontRunners website
24. The Carotenoids page
25. The Bioflavonoids Page
26. Alternative Medicine Review 2000 (Dec); 5 (6): 530-545