The Elephant-Sized Flaw in Large Clinical Trials

Imagine you’re like me and have a genetic variation in your D2 Dopamine receptor code which makes some aspects of “executive functioning” difficult. (I was always the last one to finish my lab work in Chemistry, Biochemistry, and General Physics — though I got the highest final score in Physics Lab, so I’m not claiming to be stupid.)

Anyway, you’ve got this D2 challenge in your brain, you do some reading and discover that organic velvet bean powder has L-dopa that might help you with things like working faster through cookbook recipes.

You buy some velvet bean powder, try it and, wow, you’re not only more efficient, your mood improves.

You should feel ecstatic, right?

But no, you’re vaguely suspicious because you’re a medical doctor. Professors and attendings have warned you that anecdotal evidence is worthless, and the placebo effect is ready and waiting to make a fool of you. 

To avoid embarrassment, you decide you need a double-blinded, prospective clinical trial with a large number of test subjects and proper randomization. Anything less would be rubbish.

Fortunately, this is not a problem. You’re also a multi-billionaire who can fund a complete drug trial.

Of course, you didn’t get rich by ignoring opportunity. You plan to make money with these velvet beans. 

Knowing that your problem starts with genetic D2 variation, common sense tells you to study a few thousand people who have the same genetic makeup.

But what about your target buyer? A businessperson looks there first.

From that perspective, you want the FDA approval to apply to as many people as possible so you can hand out genetically modified velvet bean pills to the broader public and make more money.

You therefore choose the typical mainstream experimental design: Thousands of unselected participants taken in randomly and then randomized and blinded into trial and control groups. You’ll also blind the people administering the bean pills and placebos so no one can fault your study.

Ten years and 1.2 billion dollars later, the trial ends and the stats come back from the math geeks, those rare professionals who honestly understands statistics and can manipulate them dishonestly.

Despite their efforts, they bring you bad news. There is no statistical evidence that your patented velvet bean extract improves executive functioning or mood.

Rats!

You go home and glare at your dog, then apologize with an organic carrot.

If you publish the paper, the entire world of mainstream MD’s, those smart women and men who don’t read the scientific literature or think for themselves because they’re too busy and frightened of lawsuits – those dedicated, exhausted people will hear from their educators, the drug reps, that velvet beans are rubbish. “This is just another example of the functional medicine quacks peddling snake oil.”

But you take organic velvet bean powder every day, it’s made a real difference. In the kitchen now, you’re turning out Molten Lava Cakes faster than the famous TV chefs. You feel more grounded and calm, too.

What should you do?

It’s obvious, isn’t it? Common sense tells you to go back and do a clinical trial using people with the D2 receptor issue, testing the organic velvet bean powder that works for you, not the GMO stuff your lab cooked up for megabucks.

Unfortunately, this common-sense approach rarely if ever happens in the real world. Negative studies like this are routinely published, and the mainstream fails to see the elephant-sized flaw in their assumptions: the human population is vastly more diverse than previously known at the genetic and biochemical level.

Genetic diversity is relevant to every branch of medicine because single nucleotide polymorphisms (genetic SNPs), like the one that affects my D2 receptors, create a huge diversity in disease susceptibility at the root-cause level, as well as a myriad of diversity in personal strengths and weaknesses within every system of the body.

From the central nervous system to the skin, genetic SNPs are the rule, not the exception. And science has hardly begun to uncover them all or understand their complex interplay across systems.

I have another common genetic SNP that reduces my ability to “detoxify” caffeine by about 60%.

With this knowledge, I’ve lowered my caffeine intake from several double mochas a day (at the VA Med Center years ago), to two cups of green tea per day. This reversed an unbearable sensation of vascular congestion in my legs. (n=1)

I also have a SNP that makes me inefficient at converting beta-carotene to vitamin A, a few SNPs that increase my need of several B vitamins for adequate methylation to keep my homocysteine levels down, and numerous others that I won’t bore you with. But despite all my SNPs, I’m still quite healthy for 63 year-old man.

The thing is, genetic SNPs are so common, you yourself almost certainly have at least one, more likely a handful. So it’s irrational for researchers to lump you into a huge unselected “normal” population when they’re testing something. And it’s misinformed and lazy for MD’s, however busy they are, to ignore your SNPs and follow cookbook-official protocols when treating you. They need to read more broadly and act with integrity even if it costs them.

Genetic diversity is why functional medicine, imperfect as it is, will become central to mainstream medical care someday. The establishment will change the name from functional medicine to something they haven’t already disparaged.

Currently, they say functional medicine is not evidence-based. In some ways that’s true.

But when it comes to reversing chronic disease rather than just controlling its progression, functional medicine is more evidence-based than mainstream medicine because it uses personal genetic data that the mainstream ignores.

Moreover, it understands the elephant-sized flaw in the mainstream’s large clinical debunking trials. 

Morrill Talmage Moorehead, MD

Photo by Rafael on Unsplash

13 thoughts on “The Elephant-Sized Flaw in Large Clinical Trials

  1. There is an ever-increasing awareness that large scale clinical studies are very “personalized”, that is, adjusted around the interests of those who order and pay for them.
    I dare see a near future when increasingly medical care will focus on the individual body’s response, instead of on generalized mechanisms of the kind “one-size-fits-all”.

  2. The one thing I learned that I remembered most from college studies was (sadly) the numbers can always be cooked to achieve just about any outcome. *sigh* That said, if organic velvet bean powder made me feel more efficient with a better mood, I’d continue to buy it. 😉 Happy weekend.

    • I’m always reading and experimenting. (n=1) My latest thing is not an organic powder but an electronic gadget called “Omni Stimulator” intended to help people attain the “flow state” among numerous other possible effects. It sends a small direct current across the skull into the cerebral cortex. I’ve read papers about this technology so I thought I’d better try it out for myself. It’s too soon to report, but preliminary results are favorable. I’ll keep you posted. 🙂

            • Thank you, that’s so kind of you. I bought the Omni Stimulator from a guy in Australia. Here’s his site: https://www.omnistimulator.com/. It arrived two days ago, so I’ve only used it twice. It took forever getting here, probably because of customs. Most of the powders and over-the-counter organic herbs and potions I’ve experimented with come through Amazon. Many of those things are based upon Dale Bredesen’s protocol to keep the mind sharp and avoid dementia (“The End of Alzheimer’s). He’s a true scientist, despite having an MD behind his name. Here’s his site: https://www.ahnphealth.com/dr-bredesen.html. I can only experiment on myself, of course. But if you run any experiments on yourself I’d love to hear your results. Knowledge is expanding faster than anyone can keep up. But I love trying. 🙂

                • Hi, I”m back from weeding my garden.

                  It happens that I lost at least 30 or 40 pounds without trying on a mostly vegetarian, no grains ketogenic diet. After a while I was never hungry. The problems with that for me included my propensity for calcium oxalate kidney stones and the fact that I lost too much weight and muscle mass. I should have eaten more food, but I was just never hungry and the mental clarity and energetic mood lift of ketosis was amazing for me until I got too skinny to produce any more ketones. Now I’m on a low carb, no sugar, circadian lifestyle “diet.” It’s not really a diet because I’m never planning to go back to eating the usual American level of carbohydrate intake or eating late. It seems that everything the traditional diet “experts” tells us about the evils of saturated fat is true, but only if you don’t apply it to fats and instead apply it to carbohydrates, which indeed do cause the body to store lipids, develop type 2 diabetes, heart disease and countless other problems, including brain fog and some aspects of dementia. Here’s a long, somewhat technical, but excellent video on all things circadian:

                  Rhonda Patrick is a PhD scientist with the kind of open mind that has earned my complete admiration and respect, by the way. I highly recommend all her videos if you’re interested in cutting edge health science. 🙂

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.