Medical Marijuana and “What’s the Harm

Recently I posted this article on my Facebook: Marijuana Beliefs Outstrip Evidence. I summarized a key point thus, “The only use for which marijuana has reasonably good evidence of effectiveness is for nausea.”

Note, I am all for removing marijuana from schedule 1 of FDA regulation and allowing for comprehensive research of the ways in which marijuana derived substances can be used medically. However I am firmly of the belief that they should go through the exact same FDA process as all other drugs.

The responses I got were predictable. One of the key points made by many was that if it helps people then what’s harm? I am going to set aside the point that it’s not helping most users and focus on the old “what’s the harm?” gambit. It is a standard part of the responses to criticism of alternative medicine.

So, What is the Harm?

If a treatment is just a placebo, and does not provide actual benefits then these are the harms that may result:

Money. These are hardly ever free. And especially in a country where medical expenses are the most common cause of personal bankruptcy the cost of a treatment that doesn’t work is harm.
Time. The time spent going and getting a treatment done, transportation etc. are all costs for the patients and these are things that have a tangible monetary value and therefore refer back to the above point. Is the patient giving up time at work spending, money on transportation and so on? If so that is a very real harm.
Delayed treatment. If a person delays getting effective treatment because they mistakenly believe that this placebo is actually treating their condition then that is an unambiguous harm which has demonstrable negative effects in a wide variety of diseases.
Side effects. Marijuana very clearly has side effects if we are viewing it as a medicinal substance. It is used specifically for its mind-altering effects. Remember the point of this drug originally was that it got you high, that you are stoned while you’re taking it. This is incompatible with most jobs. And even when it’s not it’s still constitutes a set of risks. FDA-approved drugs go through a risk assessment process comparing the benefits to the risks. And as detailed in the linked article above there are very clearly side effects from marijuana use.
Purity and content testing. FDA approved drugs are rigorously tested for their purity, that is their absence of toxic substances and adulteration. As well as that the medication actually contains what it says on the package. Marijuana for medical purposes lacks all of these protections.
Addiction potential. While marijuana does not have the same addictive properties that opioids do it still possesses a risk of becoming habit forming, as can any behavior, especially when it is a mind-altering one such as marijuana use.

This list is not intended to be comprehensive. But does at least hit the highlights of the potential harms of medical marijuana.

An additional range of harms from the current approach to medical marijuana also includes the fact that it increases the danger to children for accidental ingestion and poisoning, especially with the prevalence of edibles and related products that are in similar packaging and have similar names to candy, as detailed here: More Marijuana More Problems for Young Children.

Conclusion

Ultimately, my position on this topic is that all medical treatments should be subject to a uniform study and approval process. The FDA is not perfect but they have a very good track record. The objective should be to lobby for marijuana to be removed from Schedule I, not to create a carve out from regulation where marijuana gets a free pass written by legislators.

Links: Processed Food and Disease

One of the other blogs I follow is the Angry Chef. I aspire to be as entertaining as that blog. But also to be seen as serious – which I think are mutually exclusive goals.

Recently posted was a two-parter about “Ultra-Processed Foods” and the dietary guidelines of Brazil and the World Health Organization.

Rise of the Ultra Foods, part 1 and part 2.

I encourage you to read them. But the short version is that the new nutrition guidelines of Brazil have a lot of positive characteristics about them. They encourage enjoying food, acknowledge the cultural and familial components of eating and meal times. These are good things. But they also go off on the concept of ultra-processed foods. Which is never defined. And the available evidence just doesn’t support the idea that UPF are inherently problematic

There exists this anti-chemical strain of though that modern processing of food is intrinsically bad. Because chemicals or something. That somehow the rise of lifestyle diseases like cardiovascular disease and diabetes are because of the chemicals and not calories and poverty.

There is already an enormous body of evidence that calories consumed are the primary driver of increased lifestyle diseases. And that the biggest confounder in this type of research is the known effect of poverty on health outcomes as well as on food choices/availability.

All of the various safety studies of chemicals used in processing food fail to show any evidence of harm.

Why then should we consider the idea that the “real” problem is processed foods? Well, as The Angry Chef points out, at least one researcher is actually performing a study to address this question. As opposed to just blaming the chemicals. It’s a randomized controlled study comparing matched diets of processed and not processed foods. Here’s the study at ClinicalTrials.gov.

I await the results of this study. And will update my understanding of the topic based on the results if they show that I’ve been wrong so far.

Benefits of Strength Training

I’ve written before about the benefits of strength training, on my previous blog. Now recent research backs up one of the reasons I’ve long suspected.

As I’ve brought up before, it’s important not to over-interpret preliminary evidence or attempt to extrapolate from basic science to clinical reality. So while I’ve long suspected that strength training would have a benefit when it comes to diabetes development, I’ve avoided actually saying that.

And so it’s always nice when the clinical studies back up what I suspected. Hooray!

One of the things I learned from my exercise physiology education was that strength training upregulates GLUT4 on muscle cells. GLUT4 is an insulin triggered transporter for glucose. This means that strength training increases the ability and sensitivity of the of the muscle cell to take glucose out of the bloodstream and put it in the muscle cell.

Theoretically, this should reduce the likelihood of diabetes. But does it?

To the research!

I recently came across this study from JAMA: A Prospective Study of Weight Training and Risk of Type 2 Diabetes Mellitus in Men. The large Health Professionals Follow-up Study was used to track physical activity in 32,002 men for 18 years. Any physical activity reduced the risk of developing or dying from diabetes. Strength training was more effective than cardiovascular training. Both was better than just one.

Things to note about why this research is notable for this conversation:

The size of the study. Tens of thousands of subjects followed for nearly 2 decades is a lot.
The effect sizes are large. For relative risk, reducing the number of cases by up to 1/3, of one of the most common and expensive lifestyle modifiable diseases, is a big deal.
P value was tiny. P < .001. This wasn’t one of those, “if I hack it I can get P to equal .05” types of studies.
Dose response. There is a clear, fairly linear, dose response of more weight training leads to lower risk.
Normal living humans. Study was conducted on humans. The people were not having their lives dictated to them by researchers.

The best results were seen at 150+ minutes per week of weight training, cardiovascular exercise and for both. This may seem like a lot, but it’s hitting the gym 3 times a week and going for a 30 minute brisk walk most days.

There are limitations to the study, of course. It’s not randomized, but the best studies of this type of question can’t be because it’s hard to control behavior for that long in free-living humans. It’s only in men. Weight training is not necessarily defined the same as strength training.

Conclusion

As I’ll keep saying, the best outcomes result from a complete approach to physical activity which includes strength training, cardiovascular exercise, flexibility/range-of-motion and neuromotor (balance/agility) training.

Reference

Grøntved, A., Rimm, E. B., Willett, W. C., Andersen, L. B., & Hu, F. B. (2012). A Prospective Study of Weight Training and Risk of Type 2 Diabetes Mellitus in Men. Archives of Internal Medicine, 172(17), 1306–1312. https://doi.org/10.1001/archinternmed.2012.3138

Oh no, Carbs

(Updated for clarity based on Facebook feedback)

There is a lot of hullabaloo about carbs in nutrition circles, especially in clean eating types of diets. Especially if those carbs are from sugar. And extra especially if that sugar is high-fructose corn syrup. But the reality is that for weight loss and general health goals* carbs are not, in and of themselves, a big deal.

The science is clear that low carb and low fat diets produce the same long term outcomes when measuring weight loss. These two links do a good job of addressing this:

Low Fat vs Low Carb – No Difference

Sorry, but Low Carb and Low Fat Diets Get Pretty Much the Same Results

This is the study being discussed: Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion

So, rather than repeat that content, I want to address why this is the more reliable research. Because, of course, there will be replies about research showing that low carb works better.

To analyze diet science we need to look at a couple of factors:

Time

How long was the study? Any study of just a few months can show weight loss. The reality is that if you can’t show weight loss in a 12-16 week study then you are just bad at your job. Any possible diet strategy can show weight loss in this time frame. Such results are meaningless to this conversation.

The health outcomes that are important for this kind of research are ones that evolve over the course of decades. Some of the landmark studies in this field have been running longer than most of my readers have been alive.

So let’s be clear. 6 months or less is short. Too short for me to care about. Too short to inform human interventions. 1 year is the bare minimum to matter.

But why are studies like this even done if they are not meaningful? Well, they are preliminary research. Preliminary research plays an important role in the process of science but they are clearly not the end point. News stories about them are usually counterproductive and they shouldn’t be used to guide interventions in humans.

A preliminary study might just be used to determine in an approach is feasible, or to determine dosing, safety and similar characteristics. But they don’t tell us if an intervention works.

There is, of course, another more cynical reason for short-term diet studies: using them to sell stuff. Since positive results are just about guaranteed in a short-term study they create an easy way to apply the “clinically proven” sticker to your diet and resist FTC objections.

Petri Dishes and Animals

A lot of the objection to sugar and carbs is the result of a belief that calories from those sources are particularly bad for human health compared to protein or (good) fats. However, this comes pretty much entirely from research in petri dishes or animal studies.

Again this is another example of over-interpreting preliminary research. The results of applying a substance directly to a cell in a petri dish cannot be generalized to the whole human body. There are so many other factors at play in understanding how a substance will affect clinical outcomes. How is it digested? How does it interact with other substances in the body? How do homeostatic mechanisms operate to limit any changes? Etc.

And while animal research is a useful step in health research for humans we are, forgive me for stating the obvious, not mice. Or rats. Or guinea pigs. Or regular pigs. Or even monkeys. The question of what animal are we most like, a mouse or a rat, suffers from the fact that it depends on what part of the human system you are studying. And even then, we cannot just blithely assume that any animal results will apply to humans.

Biomarkers!

An extension of the last point is research into biomarkers. In short biomarkers are substances found with chemistry tests that are thought to indicate a particular (disease) state. Some are well validated, like troponin for a heart attack, others are not, like telomere length for aging. It is important to understand that a biomarker is correlated to the state of the body and is not a direct measure of the state of interest. They can be suggestive, but they don’t always predict actual health outcomes.

One of the most commonly misused biomarkers are any markers for inflammation. The assumption being that such markers indicate that something Bad is happening. So if eating sugar boosts the levels of some inflammatory biomarkers it must be terrible for you! But the research into actual health outcomes – death, disability etc. – doesn’t bear this out. Sure, eating too many calories leads to problems but the source of those calories doesn’t actually predict outcomes.

Conclusion

Yes it’s calories. Clearly though, understanding that is not the hard part. Behavior change is the hard part. Establishing new eating patterns and habits is the hard part. Fad diets that focus on one, or a few, components like sugar or carbs attempt to create the impression that it’s what you eat, not how much, that really matters. And it’s just not true.

* General health goals = is the phrase I’m using to mean premature death and disability/loss of function due to lifestyle modifiable diseases and risk.

“The Dirty Dozen” – Brief Response to News

(We’ll see if this becomes a regular thing for this blog)

The Environmental Working Group released its annual Dirty Dozen list again. They are a non-scientific group of scaremongers. This list of theirs epitomizes this fact. They take the publicly available USDA data on pesticide residue and then report characteristics like the number of different residues found and the amount of those residues. Then they rank grocery store produce based on these numbers.

What they never do is compare those values to the actual amounts necessary to harm a person. Because if they did, they’d look silly. For instance you’d have to eat 10 kilograms a day of strawberries just to reach the low end of minimum appreciable risk (RfD). (I got the math from here.)

The techniques used to detect pesticide residue are incredibly sensitive. Far more sensitive than necessary for human health. The tiniest amounts can be detected. But those tiny amounts need to be compared to results from toxicology studies to have any meaning.

The Environmental Working Group also asserts, without evidence, that a wider variety of pesticides on a plant is somehow intrinsically more dangerous than just one pesticide. This statement might be true – different chemicals may interact to be more dangerous than toxicology research on a single chemical indicates. But no evidence suggests that it is. And human health is carefully tracked by the CDC.

And even if more chemicals on the plant is more dangerous they fail to take into account the fact that the plant already has thousands of different chemicals inside. At at much higher concentrations than the pesticides. And those plant chemicals include substances evolved to kill other life forms to protect the plant i.e. pesticides. There is more of those pesticides than the ones applied by farmers.

In short, their list has nothing to do with known toxicology information. It is just an attempt to scare people. And CNN and other media swallowed it whole.