Peter Doshi On The Risk Of Labels

Peter Doshi in the BMJ, 2017:

Labeling people concerned about the safety of vaccines as “anti-vaccine” risks entrenching positions. The label (or its derogatory derivative “anti-vaxxer”) is a form of attack. It stigmatizes the mere act of even asking an open question about what is known and unknown about the safety of vaccines.

The label too quickly assumes that there are “two sides” to every question, and that the “two sides” are polar opposites. This “you’re either with us or against us” thinking is unfit for medicine.

COVID Vaccines – Comparison Chart

Here’s a chart that Peter Doshi included in his article in the BMJ. (Click to enlarge.)

Table 1
Characteristics of ongoing phase III covid-19 vaccine trials


Source: Will Covid-19 Vaccines Save Lives? Current Trials Aren’t Designed To Tell Us, British Medical Journal, 21 October 2020

What he said about this chart:

Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, said, “Ideally, you want an antiviral vaccine to do two things … first, reduce the likelihood you will get severely ill and go to the hospital, and two, prevent infection and therefore interrupt disease transmission.”7

Yet the current phase III trials are not actually set up to prove either (table 1). None of the trials currently under way are designed to detect a reduction in any serious outcome such as hospital admissions, use of intensive care, or deaths. Nor are the vaccines being studied to determine whether they can interrupt transmission of the virus.

It’s not that the vaccines aren’t able to reduce severe illness, reduce deaths, or stop transmission. It’s that the trials cannot tell us that. They would have had to be longer. (If someone is saying these vaccines save lives, well, that’s not the science.) And long trials were not compatable with “Operation Warp Speed.”

I also noted that pregnant or breastfeeding women and immunocompromised patients were excluded. Who knows how these vaccines will affect them? No data.

One Ingredient In COVID Vaccines That May Be Causing Allergic Reactions: Polyethylene Glycol (PEG)

The active ingredient in MiraLAX, a popular over-the-counter laxative and bowel prep for colonoscopies is polyethlyene glycol (PEG). If you have used any products containing PEG in the past, you may have developed anti-PEG antibodies. That could increase your risk of experiencing an immune reaction when you receive the PEG-containing Pfizer or Moderna vaccines.

The new COVID-19 vaccines by Pfizer/BioNTech and Moderna contain polyethylene glycol (PEG), a common ingredient in skin care products and laxatives. Anti-PEG antibodies are found in people who have been exposed to PEG. Upon re-exposure, those antibodies can elicit an immune response with effects that range from mild to severe.

In the study below, 72% of contemporary human samples contained anti-PEG antibodies. That’s a lot! The authors advise screening patients prior to “administration of therapeutics containing PEG.”

Analysis of Pre-Existing IgG and IgM Antibodies Against Polyethylene Glycol (PEG) In The General Population, Analytical Chemistry, December 2016

Circulating antibodies (Ab) that specifically bind polyethylene glycol (PEG), a biocompatible polymer routinely used in protein and nanoparticle therapeutics, have been associated with reduced efficacy of and/or adverse reactions to therapeutics modified with or containing PEG.

Unlike most antidrug antibodies that are induced following initial drug dosing, anti-PEG Ab can be found in treatment-naïve individuals (i.e., individuals who have never undergone treatment with PEGylated drugs but most likely have been exposed to PEG through other means).

Unfortunately, the true prevalence, quantitative levels, and Ab isotype of pre-existing anti-PEG Ab remain poorly understood. Here, using rigorously validated competitive ELISAs with engineered chimeric anti-PEG monoclonal Ab standards, we quantified the levels of anti-PEG IgM and different subclasses of anti-PEG IgG (IgG1-4) in both contemporary and historical human samples.

We unexpectedly found, with 90% confidence, detectable levels of anti-PEG Ab in ∼72% of the contemporary specimens (18% IgG, 25% IgM, 30% both IgG and IgM).

Anti-PEG Ab’s were also observed in ∼56% of serum samples collected during 1970-1999 (20% IgG, 19% IgM, and 16% both IgG and IgM), suggesting that the presence of PEG-specific antibodies may be a longstanding phenomenon.

The widespread prevalence of pre-existing anti-PEG Ab, coupled with high Ab levels in a subset of the population, underscores the potential importance of screening patients for anti-PEG Ab levels prior to administration of therapeutics containing PEG.

Having anti-PEG antibodies can lead to another unwanted effect. Those antibodies can attack the vaccine (PEG is used as a coating to keep the vaccine from degrading), resulting in reduced vaccine effectiveness:

“… it is increasingly recognized that treating patients with PEGylated drugs can lead to the formation of antibodies that specifically recognize and bind to PEG (i.e., anti-PEG antibodies). Anti-PEG antibodies are also found in patients who have never been treated with PEGylated drugs but have consumed products containing PEG. Consequently, treating patients who have acquired anti-PEG antibodies with PEGylated drugs results in accelerated blood clearance, low drug efficacy, hypersensitivity, and, in some cases, life-threatening side effects.
The Importance Of Poly(ethylene glycol) Alternatives For Overcoming PEG Immunogenicity In Drug Delivery And Bioconjugation, Polymers, February 2020

Increasing Protein Intake After Age 65: Not Necessary, May Be Harmful

Here are all the studies Greger cites in his video. It’s worth watching; he condenses the core message in these 14 studies into a 6-minute, easy-to-understand video. (Transcript at the bottom.)

Low Protein Intake Is Associated With A Major Reduction In IGF-1, Cancer, And Overall Mortality In The 65 And Younger But Not Older Population, Cell Metabolism, March 2014

Among subjects with no diabetes at baseline those in the high protein group had a 73-fold increase in risk, while those in the moderate protein category had an almost 23-fold increase in the risk of diabetes mortality.

Evidence-based Recommendations For Optimal Dietary Protein Intake In Older People: A Position Paper From The PROT-AGE Study Group, The Journal of Post Acute and Long-Term Care Medicine, July 2013

Meta-analysis Of Nitrogen Balance Studies For Estimating Protein Requirements In Healthy Adults, American Journal of Clinical Nutrition, January 2003

Dietary Protein Requirements Of Younger And Older Adults, American Journal of Clinical Nutrition, November 2008

This study provides the most comprehensive nitrogen balance–based assessment of the protein needs of older men and women ever published. The results indicate that the requirement for dietary protein is not different between apparently healthy younger and older adults, and that the recommended dietary allowance of 0.8 g protein · kg body wt−1 · d−1 is adequate to meet the minimum dietary needs of virtually all older persons.

Is The Optimal Level Of Protein Intake For Older Adults Greater Than The Recommended Dietary Allowance?, The Journals of Gerontology: Series A, June 2013

Conflict of Interest: E. Volpi: travel support from Abbott and Nestle. W. Campbell: member of the Whey Protein Advisory Panel for the National Dairy Council. R.R. Wolfe: consultant for the National Cattlemen’s Beef Association

Aging Of Skeletal Muscle: A 12-yr Longitudinal Study, Journal of Applied Physiology, April 2000

Dietary Protein And Muscle In Older Persons, Current Opinion in Clinical Nutrition and Metabolic Care, January 2014

Age‐Related Changes In Skeletal Muscle Mass Among Community‐Dwelling Japanese: A 12‐Year Longitudinal Study, Geriatrics and Gerontology, January 2014

Moderately Increased Protein Intake Predominately From Egg Sources Does Not Influence Whole Body, Regional, Or Muscle Composition Responses To Resistance Training In Older People, The Journal of Nutrition, Health and Aging, April 2009

Conclusion: Consumption of diets that contained moderately higher protein … did not differentially affect body composition, skeletal muscle fiber size, or serum lipid-lipoprotein profile responses to resistance training in older people. (Study funded by American Egg Board. If they could have promoted eggs, they would have!)

Dietary Protein And Resistance Training Effects On Muscle And Body Composition In Older Persons, Journal of the American College of Nutrition, December 2007

Most of the limited research suggests that resistance training-induced improvements in body composition, muscle strength and size, and physical functioning are not enhanced when older people who habitually consume adequate protein (modestly above the RDA) increase their protein intake by either increasing the ingestion of higher-protein foods or consuming protein-enriched nutritional supplements. (Study funded by the National Dairy Council. Again, if they could have promoted dairy, they would have!)

Association Between Healthy Diet And Exercise And Greater Muscle Mass In Older Adults, Journal of the American Geriatrics Society, April 2015

Consuming recommended levels of vegetables was associated with 48% lower odds of low muscle mass and engagement in recommended levels aerobic exercise with 38% lower odds. (Note diet had a greater impact than exercise.)

The alkalizing effects of vegetables may neutralize mild metabolic acidosis, which has catabolic effects on muscle.

Alkaline Diets Favor Lean Tissue Mass In Older Adults, American Journal Of Clinical Nutrition, March 2008

Muscle wasting appears to be an adaptive response to acidosis.

Diet-induced Acidosis: Is It Real And Clinically Relevant?, British Journal of Nutrition, December 2009

Chronic ‘low-grade’ acidosis is thought to be brought about primarily by two factors: advancing age with a consequent decline in renal function, and diet, which may promote acidosis by both its net acid load, as well as its sodium chloride content.

A Higher Alkaline Dietary Load Is Associated With Greater Indexes Of Skeletal Muscle Mass In Women, Osteoporosis International, November 2012

This study found a more alkaline diet was positively associated with muscle mass in women suggesting a role for dietary acid–base load in muscle loss.

Video Transcript:

That study that purported to show that diets high in meat, eggs, and dairy could be as harmful to health as smoking supposedly suggested that people under 65 who eat lots of meat, eggs, and dairy are four times as likely to die from cancer or diabetes. But if you look at the actual study, you’ll see that’s simply not true. Those eating lots of animal protein didn’t have four times more risk of dying from diabetes; they had 73 times the risk.

What about those that chose moderation, those in the moderate protein group, who got 10 to 19% of calories from protein? They just had about 23 times the risk of death from diabetes, compared to those consuming the recommended amount of protein, which comes out to be about 6 to 10% of calories from protein—around 50 or so grams a day.

So, the so-called low protein intake is actually the recommended protein intake—associated with a major reduction in cancer, and overall mortality in middle age, under age 65. But note, it says not in older populations. When it comes to diabetes deaths, lower overall protein intake is associated with a longer life at all ages. But for cancer, it seems to flip around age 65.

These results suggest that low protein intake during middle age, followed by moderate to high protein consumption in old adults, may optimize healthspan and lifespan. Some have suggested that the standard daily allowance for protein, 0.8 grams of daily protein for every healthy kilogram of body weight, may be fine for most, but maybe older people require more.

This is the study upon which the RDA was based, and though there was a suggestion that the elderly may have a somewhat higher requirement, there is just not enough evidence to make different recommendations. The definitive study was published in 2008, and it found no difference in the protein requirements between young and old. The same RDA should be adequate for the elderly.

But adequate intake is not necessarily optimal intake. The protein requirement studies don’t address the possibility that protein intake well above the RDA could prove beneficial—or so suggests a member of the Whey Protein Panel, and a consultant for the National Cattlemen’s Beef Association.

If you follow sedentary individuals over the age of 65, they lose about 1% of their muscle mass every year. If you force people to lie in bed all day for days at a time, anyone would lose muscle mass. But older adults may lose muscle mass on bed rest six times faster than young people. So, it’s use it or lose it for everyone, but the elderly appear to lose it faster; so, they better use it.

The good news is, in contrast to the 12-year U.S. study, a similar study in Japan found that the age-related decreases in muscle mass were trivial. Why the difference? It turns out the participants were informed about the results of their muscle strength; and so, often tried to improve it by training before the next exam for the study—especially the men, who got so competitive their muscle mass went up with age, which shows that the loss of muscle mass with age is not inevitable; you just have to put in some effort.

And, adding protein does not seem to help. Adding more egg whites to the diet did not influence the muscle responses to resistance training—and that’s based on studies funded by the American Egg Board itself. Even the National Dairy Council couldn’t spin it; evidently, strength training induced improvements in body composition, muscle strength and size, and physical functioning are not enhanced when older people increase their protein intake by either increasing the ingestion of higher-protein foods, or taking protein supplements.

Is there anything we can do, diet-wise, to protect our aging muscles? Vegetables. Consuming recommended levels of vegetables was associated with cutting the odds basically in half of low muscle mass. Why? The alkalizing effects of vegetables may neutralize the mild metabolic acidosis that occurs with age, and, you know, it may be that little extra acid in our body that facilitates the breakdown of muscle.

I’ve talked about this before, how muscle wasting appears to be an adaptive response, to acidosis. We appear to get a chronic low-grade acidosis with advancing age because our kidneys start to decline, and because we may be eating an acid-promoting diet—which means a diet high in fish, pork, chicken, and cheese, and low in fruits and vegetables. And, as you can see, beans and other legumes are the only major source of protein that’s alkaline- instead of acid-forming. And indeed, a more plant-based diet, a more alkaline diet, was found to be positively associated with muscle mass in women aged 18 through 79 years old.

So, if we are going to increase our protein consumption after age 65, it would be preferable to be plant-based proteins to protect us from frailty. No matter how old we are, a diet that emphasizes plant-based nutrition is likely to maximize health benefits in all age groups.

Related:
How To Preserve Muscle And Bone As We Age: Eat Less Meat And Dairy, More Fruits And Vegetables

Here’s a chart Greger included in his video. You want to eat more foods on the right side and fewer foods on the left. The effects of an alkaline diet are so good at preserving muscle that athletes are known to supplement with sodium bicarbonate, a.k.a. baking soda. Eating a plant-based diet gives you that benefit without all the sodium and stomach upset.

World Health Organization: Vaccines May Not “Prevent People From Actually Getting The Infection”

World Health Organization chief scientist Soumya Swaminathan said:

I don’t believe we have the evidence on any of the vaccines to be confident that it’s going to prevent people from actually getting the infection.

What is a vaccine then? If not to prevent infection?

She also said:

I would say in a four to five-year timeframe we could be looking at controlling this.

I do not understand how these vaccines can contribute to herd immunity when they may not even provide immunity. When they may not prevent transmission.

In the spring, when the weather warms and people go back outside, will the case numbers drop? Will fewer cases be a result of weather or vaccinations?

Nonetheless, even with an effective vaccine, even with herd immunity, “the destiny of the virus is to become endemic,” that is, regularly found in populations for several years.

The COVID Vaccines Were Not Designed To Stop Transmission Or To Prevent Serious Illness

Getting the vaccine does not mean you can’t get infected, get very sick, or transmit the virus to others. That’s why, according to the CDC, you have to continue wearing a mask and social distancing. The vaccine was only designed to lessen mild symptoms. It was not designed or tested to prevent serious illness or to prevent transmission. The vaccine manufacturers should be making this point more forcefully in the media.

Will Covid-19 Vaccines Save Lives? Current Trials Aren’t Designed To Tell Us, British Medical Journal, 21 October 2020

Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, said, “Ideally, you want an antiviral vaccine to do two things . . . first, reduce the likelihood you will get severely ill and go to the hospital, and two, prevent infection and therefore interrupt disease transmission.”7

Yet the current phase III trials are not actually set up to prove either (table 1).

None of the trials currently under way are designed to detect a reduction in any serious outcome such as hospital admissions, use of intensive care, or deaths. Nor are the vaccines being studied to determine whether they can interrupt transmission of the virus.

Yet until vaccine manufacturers began to release their study protocols in mid-September, trial registries and other publicly released information did little to dispel the notion that it was severe covid-19 that the trials were assessing. Moderna, for example, called hospital admissions a “key secondary endpoint” in statements to the media.15 And a press release from the US National Institutes of Health reinforced this impression, stating that Moderna’s trial “aims to study whether the vaccine can prevent severe covid-19” and “seeks to answer if the vaccine can prevent death caused by covid-19.”16

But Tal Zaks, chief medical officer at Moderna, told The BMJ that the company’s trial lacks adequate statistical power to assess those outcomes. “The trial is precluded from judging [hospital admissions], based on what is a reasonable size and duration to serve the public good here,” he said.

“Our trial will not demonstrate prevention of transmission,” Zaks said, “because in order to do that you have to swab people twice a week for very long periods, and that becomes operationally untenable.”

Great uncertainty remains over how long a randomised trial of a vaccine will be allowed to proceed. If efficacy is declared, one possibility is that the thousands of volunteers who received a saline placebo would be offered the active vaccine, in effect ending the period of randomised follow-up. Such a move would have far reaching implications for our understanding of vaccines’ benefits and harms, rendering uncertain our knowledge of whether the vaccines can reduce the risk of serious covid-19 disease and precluding any further ability to compare adverse events in the experimental versus the placebo arm.

If frail elderly people, who are understood to die in disproportionate numbers from both influenza25 and covid-19, are not enrolled into vaccine trials in sufficient numbers to determine whether case numbers are reduced in this group, there can be little basis for assuming any benefit in terms of hospital admissions or mortality.

This is hard to evaluate in the current trials because there are large gaps in the types of people being enrolled in the phase III trials (table 1). Despite recruiting tens of thousands, only two trials are enrolling children less than 18 years old. All exclude immunocompromised people and pregnant or breastfeeding women, and though the trials are enrolling elderly people, few or perhaps none of the studies would seem to be designed to conclusively answer whether there is a benefit in this population, despite their obvious vulnerability to covid-19.

Al Sommer, dean emeritus of the Johns Hopkins School of Public Health, told The BMJ, “If they have not powered for evidence of benefit in the elderly, I would find that a significant, unfortunate shortcoming.”

One view is that trial data should be there for all target populations. “If we don’t have adequate data in the greater than 65 year old group, then the greater than 65 year old person shouldn’t get this vaccine, which would be a shame because they’re the ones who are most likely to die from this infection,” said vaccinologist Paul Offit.8 “We have to generate those data,” he said. “I can’t see how anybody—the Data and Safety Monitoring Board or the FDA Vaccine Advisory Committee, or FDA decision-makers—would ever allow a vaccine to be recommended for that group without having adequate data.”

“I feel the same way about minorities,” Offit added. “You can’t convince minority populations to get this vaccine unless they are represented in these trials. Otherwise, they’re going to feel like they’re guinea pigs, and understandably so.”