I have always had a bias towards the Appeal to Nature Fallacy:
An Appeal to Nature Fallacy happens when someone argues that something is good, better, or more authentic simply because it’s natural, while brushing aside anything man-made as inferior or harmful.
Or last my version of it.
I have always thought of the human body as more or less tuned by evolution to run optimally. More or less. I know there are those who marvel at the human body, but after 40 years as a doctor, I am more amazed that this kludge of half-assed systems, mutations, and polymorphisms that is a human can survive at all. The only organ that functions adequately in my meat sack is my liver, and that is because I exercise it regularly. Or am I over-sharing?
Be it sodium or temperature or hematocrit or whatever, physiology keeps the value in a tight range. I assume the value is an optimal trade-off between benefits and complications. If we had a core temperature of 103, humans would likely have fewer infections, but the caloric requirements to maintain that temperature would be prohibitive.
Among the many physiologic half assitudes of being human is we have lost the ability to synthesize some vitamins (vitamins A and C) or we have moved to parts of the world that make that synthesis more difficult. Long periods of gray skies here in the great Pacific NW make vitamin D synthesis problematic.
So for these, and other vitamins, we have to rely on diet to stay replete, and evolution has determined what those optimal vitamin levels should be. Much of the world can’t run over to Safeway and get a varied diet to prevent vitamin deficiency. Not that always helps to live in the US. Many people in the US live in food deserts or have food peccadilloes that get in the way of good nutrition. Years ago I saw a patient who for years ate only white rice and had high-output heart failure from thiamine deficiency. That takes real commitment to achieve.
I have always had an interest in vitamins, specifically as they relate to infectious diseases. For those stumbling upon this blog for the first time, I was an infectious disease doctor for 36 years, hence the interest.
There are two issues concerning vitamins and infections: The consequences of deficiency and whether the vitamins can be used pharmacologically to help treat infections.
It is an interesting literature. For vitamins C and D I will sum up, as they are not the focus of this entry: Deficiency in either increases risks for a variety of infections in a variety of populations. In deficient populations, treatment does not always have a clear-cut benefit. In replete populations, supplementation likely does little and supratherapeutic doses do less. It’s like oil in your car. You want the oil at the optimal level on the dipstick and there is no point in adding 7 quarts when the capacity of the crankcase is 6. Many a crank fails to make a case for supratherapeutic doses of vitamins. Although I made sure my TB patients took vitamin D, even if the literature is messy.
But the vitamin treatment du jour is vitamin A and measles. So what’s the deal?
First, vitamin A and the immune system. Does it boost? Of course not. But vitamin A is important for the function of many physiologic functions. Should you be low on Ambien, a nice review notes:
Vitamin A (VitA) is a micronutrient that is crucial for maintaining vision, promoting growth and development, and protecting epithelium and mucus integrity in the body. VitA is known as an anti-inflammation vitamin because of its critical role in enhancing immune function. VitA is involved in the development of the immune system and plays regulatory roles in cellular immune responses and humoral immune processes.
impaired antibody responses to challenge with protein antigens, changes in lymphocyte subpopulations, and altered T- and B-cell function.
All bad if infected with measles, or any pathogen, so like all vitamins, it is good to be replete.
And more is not better, as there is vitamin A toxicity, an issue with all fat-soluble vitamins. And Americans do have a lot of fat to store vitamins.
So being deficient impairs the immune response to measles, and measles is an infection that whacks the immune system, a bad combination. As an example
measles infection can greatly diminish previously acquired immune memory, potentially leaving individuals at risk for infection by other pathogens. These adverse effects on the immune system were not seen in vaccinated children.
wipes out 11 percent to 73 percent of the different antibodies that protect against viral and bacterial strains a person was previously immune to — anything from influenza to herpesvirus to bacteria that cause pneumonia and skin infections.
And during acute infections is a cause of neutropenia, aka low white cell counts.
As a result of that gruesome twosome, vitamin A deficiency leads to worser outcomes in measles with more death and more blindness. Given that vitamin A deficiency is common in much of the world, I was curious about Samoa, where 83 of 5,707 with measles died (1.4%), more than the usual 1 in 1000. People think a 1 in a 1000 chance of death is low. As a thought experiment, I do not think I would hold a gun to my head and pull the trigger if there was a 1:1000 chance of blowing my brains out. But that’s me.
Clinicians reported that Vitamin A deficiency or immunodeficiency did not appear to be a substantial contributing factor to the outbreak.
But the reference is useless:
“We’re not really seeing evidence of acute malnutrition,” says the British paediatrician Dr. Owens, who arrived from the UK on the same flight as me. “As I understand it, there is very little evidence of clinical vitamin A deficiency. And I’ve not met a patient yet with a defined immune deficiency.”
“As I understand it” is not the deepest of understanding or a robust reference. I usually use that phrase when I have only a superficial understanding of a topic.
The amount of vitamin A available for consumption in Samoa is, on average, about 310 mcg per capita per day, which is slightly higher than the average requirements of 282 mcg per day. Huge disparities within the population can be observed, as the level of vitamin. A available for consumption among the poor population is almost half the requirement, while richer households have access, on average, to an amount of vitamin A twice the requirement. The average quantity of vitamin A available for consumption is also well below requirements for large households with many members compared to small households.
Samoan households generally have a lower intake of vitamin A than is recommended.
Vitamin A deficiency could have been a factor for the deaths in Samoa. Of course the US is not Samoa. It might be worse.
Texas, where measles is running rampant, is not noted for either healthy diet or food security. One summary of vitamin A in the US says:
Dietary surveys indicate that many US adults are not meeting dietary requirements for vitamin A: Even when accounting for vitamin A from fortified food, which is significant, 51% of adults fall short of the EAR. In contrast, more than 94% of children and adolescents (ages 2-18 years) have vitamin A intakes equivalent to the requirement or higher. Fortified, ready-to-eat cereal and fortified milk are important sources of vitamin A for children and adolescents. NHANES has also reported serum retinol concentrations: less than 1% of the US population is deficient in vitamin A. Serum retinol concentrations can be used to assess deficiency in a population but this assay cannot assess vitamin A inadequacy because retinol concentrations decline only once liver reserves are depleted.
The raw data is there on vitamin A, but not by state. Vitamin A deficiency is fairly rare in the US. In Texas, who knows? In poor Texans with a bad diet? Who knows?
It is unlikely that vitamin A deficiency is going to be important in measles outcomes in the US, except perhaps for the poor, and in the US the poor don’t matter. And I would suppose that those most in need of supplementation, the poor and those with food insecurity, are also those least able to purchase vitamins or find vitamin A rich foods.
So how about vitamin A as a treatment?
A summary of placebo-controlled trials.
Main results
Eight trials met the inclusion criteria (2574 participants). There was no significant reduction in the risk of mortality in the vitamin A group when all the studies were pooled (RR 0.70; 95% CI 0.42 to 1.15). The evidence suggests that vitamin A in a single dose was not associated with a reduced risk of mortality. However, two doses of vitamin A (200,000 international units (IUs) on consecutive days) reduced the mortality in children aged less than two years (RR 0.21; 95% CI 0.07 to 0.66) and pneumonia‐specific mortality (RR 0.57; 95% CI 0.24 to 1.37). Two doses of vitamin A reduced the incidence of croup (RR 0.53; 95% CI 0.29 to 0.89) but not pneumonia morbidity (RR 0.92; 95% CI 0.69 to 1.22), nor diarrhea morbidity (RR 0.80; 95% CI 0.27 to 2.34). None of the studies included in this review reported any adverse effects.
Authors’ conclusions
No overall significant reduction in mortality with vitamin A therapy for children with measles was found. However two doses reduced overall and pneumonia‐specific mortality in children aged less than two years. No trials directly compared a single dose with two doses.
And studies out of Africa, where vitamin A deficiency is common and vaccination is not
A systematic review, including the use of meta-analysis was done of randomized controlled trials comparing vitamin A with placebo obtained from a systematic search of the medical literature to determine whether vitamin A prevents mortality and pneumonia-specific mortality in children with measles. We identified five trials conducted in Africa, four in hospitals and one in a community that met the inclusion criteria. There were 445 children aged 6 months to 13 years supplemented with vitamin A and 478 with placebo. There was a 39 per cent reduction in overall mortality when vitamin A was used for the treatment of measles but this was not statistically significant (relative risk 0.61; 95 per cent confidence interval 0.32-1.12). When stratified by dose, 200 000 IU of vitamin A given for 2 days was associated with a reduction in overall mortality (0.36, 0.14-0.82) and pneumonia-specific mortality (0.33, 0.08-0.92) in hospitalized children in areas with high case fatality. Greater reduction in mortality was observed in children under the age of 2 years (0.17, 0.03-0.61). On the other hand, a single dose of 200 000 IU of vitamin A was not associated with reduced mortality (1.25, 0.48-3.1). There were no trials comparing a single dose with two doses of vitamin A. There were not enough studies to separate out the individual effects of age, dose, formulation, hospitalization and case fatality in the study area. We conclude that 200 000 IU of vitamin A repeated on 2 days should be used for the treatment of measles as recommended by WHO in children admitted to hospitals in areas where the case fatality is high.
Like most viral infections, interventions are probably too late in the course of the disease to do much. Viri multiply at an amazing rate and by the time people get to the doctor, most viral infections are too advanced to alter the course with antibiotics. But if there is a reasonable chance of vitamin A deficiency, it is probably good to give the kids a couple doses of A, and other vitamins, on general principles.
And in Italy, where vitamin A deficiency is unlikely? One tomato has 17% the RDA and the average Italian eats 35 kg a year. An Italian diet looks pretty good for vitamin A.
Vitamin A does not change the clinical course of measles infection or the rate of complications in children hospitalized in a high-income country.
And vitamin A or not, I also suspect that many who die of infections have mutations that increase their chance of dying, like influenza. The human genome is chockablock full of variations, polymorphisms, that increase or decrease the risk from infections. The fault, dear RFK, is not in our vitamin A, But in ourselves, that we need vaccinations.
And vitamin A doesn’t prevent measles. Remember my appeal to nature fallacy. Measles whole purpose in life is to infect humans. Infecting you is what it has evolved to do. You think the urge to reproduce was annoying as a teenager? Try being a virus.
Measles has likely only been infecting humans for 900 years or so, jumping from rinderpest, the measles of cows and goats. Eradicated by vaccination, BTW. Or perhaps rinderpest began after a leak from an 11th century Chinese virology lab. Hard to say. But I would wager measles has not had the impact on the human genome and immunity of, say, malaria.
Take home for vitamin A and measles?
Be vitamin A replete. If you are in a Third World medical and nutritional area and could be vitamin A deficient, perhaps like worst-of-breed Texas, there may be some marginal benefit from vitamin A to treat measles. If not vaccinated, try to be replete. When a child hits the ER with measles, you don’t know their nutritional status and while some vitamin A probably will not help in the short term, but might in the long run.
It would be silly to rely on vitamin A for either prevention or treatment when we have a very effective and safe vaccine.
Remember, vaccinated people do not die of measles, do not get immune reset, and do not get sicker than shit. Unvaccinated do. Vitamin A at best, in the vitamin A deficient, decreases mortality by 39%, not the 100% decrease from vaccination.
An ounce of perversion is better than a pound of pure. No. Wait. That should be an ounce of prevention is better than a pound of cure.
Get vaccinated.