Metabolomics and Science Racketeering?

And the possible association between the attack on diets, NIH-funded research, and pharmaceutical incentives.

This is a follow-up to yesterday’s post in which I look into Hazen’s research team and consider all of their findings in an overarching manner, as well as consider possible reasons for such research to be published. Note that the information placed here is me speculating on the matter and trying to piece together bits of information, so take such information with skepticism. But also consider it as a look into some of the problems that modern science has and why people have grown to become so cynical of science in general.

Yesterday’s post for those interested:

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In my prior articles highlighting issues with the studies being put out by Hazen, et al.’s team I received some comments that these studies may be serving as a way to crack down on people’s lifestyles.

For instance, if red meat is considered to be associated with increased risk of heart disease then surely the solution is to eat less red meat. If non-nutritive sweeteners such as erythritol and xylitol are also associated with increased risk of cardiovascular disease then we should clamp down on foods containing these sweeteners. And if niacin-related metabolites are related with possible increased risk of MACE then maybe we should crack down on niacin supplements available on the market.¹

Individually each study would merit their own scrutiny. As mentioned and must be reiterated the previous studies put out by Hazen, et al. in no ways tied dietary intake of these metabolites to serum levels of said metabolites and biomarkers. The researchers didn’t make any note of intake of either niacin or the non-nutritive sweeteners. Thus, each study itself would be representative of poor correlative research that doesn’t provide anything of predictive value.

However, because this research is coming out of one team in particular this warrants something else worth considering. Again, it’s rather interesting that the reported findings of these metabolomics research seemed to focus on metabolites related to diet and supplementation. The fact that something tangential as an antibiotic was found to relate to increased risk of MACE should have caused raised some questions regarding these correlative findings.

Now, given what has occurred over the past few years there have been growing rightful skepticism regarding the nature of scientific research, in which scientific endeavors may not be done with the pure pursuit of science, but rather that financial and government incentives are helping to dictate the type of research that gets funded and published.

That is, politics can run downstream of science whereby pseudoscience and poor scholarship can be used as citations for policy-making decisions. If you happen to come across research suggesting that non-nutritive sweeteners may be linked with cardiovascular disease risk irrespective of the research quality it can then be used to provide government power to regulate and dictate the use of such sweeteners in products, thereby removing power from consumers in being able to choose products for themselves.

Again, I am usually one to show a degree of skepticism, and would have originally been skeptical of this thought if not for the fact that all of these studies seem to be derived from Hazen, et al.’s research team and tied to the Cleveland Clinic, rather than being different works from different labs across the globe.

So you could imagine my surprise when coming across an article put out by none other than the NIH reporting on Hazen, et al.’s work on niacin:

Funny that an article put out by the NIH didn’t even comment on the fact that actual niacin levels, as well as dietary/supplemental intake of niacin was never reported by Hazen, et al.’s team.

But what caught my eye was this phrase used in one of the paragraphs (emphasis mine):

To investigate, an NIH-funded research team, led by Dr. Stanley Hazen at the Cleveland Clinic, searched for products of metabolism that might contribute to CVD risk. The results appeared in Nature Medicine on February 19, 2024.

So it would appear that the NIH is helping to fund work being conducted by Hazen’s research team. Again, this itself wouldn’t be concerning given that most labs will invariably receive government funding of some king.

However, in this case it appears that Hazen’s team was awarded an NIH grant of up to $12 million in 2019 in order to conduct research into gut microbe-related metabolites such as TMAO and seeing how it relates to cardiovascular risk:

That’s a pretty big lump of change for any research team, and in the most cynical sense may make one question whether there is some motive for the studies that have been published. That is, what better way for the NIH to crack down on people’s diets than to help fund research suggesting that these things can be harmful?

I won’t say that this is definitively what is going on here, but again it seems rather coincidental that such poor research methodologies are being overlooked in order to present some sort of health hysteria.

But the coincidences don’t stop there. Remember that in yesterday’s post I included an excerpt which mentioned that Hazen has many patents under his belt. Now, many of these patents appear to be related to metabolomics and identification of metabolites through analytical means.

However, in skimming through some of the patents I also noticed some interesting ones. In particular, Hazen seems to have a few patents related to targeting TMAO production pathways with various drugs, which was referred to as “drugging the microbiome” in an older Cleveland Clinic article as they seem to target the microbiome’s production of these red meat-related metabolites. Here are some of the more recent patents:

And was even referenced within the article for the $12 million grant (emphasis mine):

Central to those discoveries was the Hazen group’s demonstration that TMAO (trimethylamine N-oxide) — a byproduct of gut bacteria formed during digestion — contributes to the development of cardiovascular disease. High blood levels of TMAO have been shown to be a powerful tool for predicting future risk of heart attack, stroke and death, according to previous research initially spearheaded by Dr. Hazen and his team, and subsequently replicated around the world. TMAO testing is now widely available and in clinical use as a result.

The team also recently reported the development of a new class of drugs that target the TMAO pathway and reduce atherosclerosis and thrombosis potential in preclinical models. “As part of the Program Project, we are seeking to further develop therapeutics that leverage new insights into the mechanistic links between the gut microbiome and cardiometabolic diseases,” Dr. Hazen notes.

So not only is TMAO and other red meat/gut-related metabolites being indicted for cardiovascular disease risk, there also appear to be medications undergoing R&D to try to target these metabolites.

Again, it seems more than incidental that a metabolite that is being associated with bad health is also being researched for possible treatments.

The problem with modern scientific research

If I were to summarize some of my many grievances with modern research I would boil it down to two phrases which highlight the reductive nature of scientific research:

If detected, then pathologize.

In essence, any biomarker or metabolite that appears elevated simultaneous to a disease can be made to be related to the disease somehow.

This is one of the greatest pitfalls of correlative research, and again one of the biggest issues I have with the work of Hazen’s team as being able to detect and correlate specific metabolites doesn’t mean that these metabolites are related or predictive of possible disease. This is also why I have such an issue with the phrase “correlation does not equal causation” because it’s a nebulous statement stated as a formality to obfuscate shoddy research methodology- it’s far more important to explain why correlations may not be related to causation.

To elaborate, just because you can detect a biomarker or metabolite doesn’t mean that it is the cause of the disease. In the case of Hazen’s work it seems just as feasible to suggest that some of these elevated biomarkers may be related to the fact that many of the participants within the Discovery Cohort had prior incidences of MACE. Wouldn’t it seem plausible to consider that prior events may explain elevated biomarkers, especially given that the researchers didn’t report on any dietary intake of these compounds? And since the elevated xylitol levels were argued to be related to endogenous production of xylitol then surely we can’t tie diet to risk of cardiovascular disease based upon this biomarker. The latter is extremely problematic because it can’t even correlate dietary intake with elevated xylitol levels, and so there are several degrees of separation before we can even make a proper correlation here.

But then why does this continue to happen in research?

Maybe researchers fall into similar habits as any human where we seek to find something to blame for whatever thing ails us. If you can at least point to something as being related to a disease then you can divert attention and funds into researching that thing, even if it may not prove useful in the end. It may allow researchers avenues to explore even though the work may not be anything meaningful in the long run.

And that brings me to the other phrase:

If pathologized, then treat.

This one is rather self-explanatory, but if you claim that some sort of biomarker is related to a disease then that means finding means of targeting that biomarker through pharmaceuticals. Create a drug or treatment that can then help reduce that biomarker even if that biomarker may not be responsible for the disease in question.

This appears to be the bedrock that forms much of the problematic research we see today. Try to find a problem and offer a solution through medicalization. It’s a dangerous bastardization of what should be an earnest pursuit of truth and knowledge that is clouded in incentivized structures.

tl;dr- The government → research → pharma pipeline

Remember that what is presented here is intended to raise questions regarding the ways in which research gets funded and studies get published. But it also highlights how media outlets can manipulate scientific research in order to produce misinformation that alters our perception of the work that is being done.

It’s the same playbook that has happened many times, including during the COVID pandemic, so everything stated here is just a repetition of the typical means of malfeasance.

In viewing some of the studies and relationships shown above we can likely collect the information into a supposed hypothetical pipeline:

1. Regulatory agencies, corporations, and other large bodies may want to crack down on specific products or lifestyles, and therefore funds work in order to target these things. For instance, if farming of red meat is argued to be bad for the environment then you may want to fund research that disincentives red meat consumption. The same goes for supplements if you want to crack down on people’s ability to take health into their own hands.

2. Researchers conduct fishing expeditions to see what they can implicate regarding poor health. The work may be of poor quality, low correlative and predictive value, but nonetheless still gets published. In this case researchers may tie red meat metabolites and non-nutritive sweeteners to increased risk of cardiovascular disease even if the researchers didn’t know how much red meat or non-nutritive sweeteners their participants consumed. So even though the link between a dietary agent and the risk of disease is shoddy at best publications may still pick up the work.

3. Media outlets report on the shoddy work, putting out misinformation which falsely links some sort of dietary agent to disease. As several outlets spew out the same misinformation a false assumption is made that the underlying research is accurate- “all of these outlets can’t be wrong, can they?” Thus the public is misled due to lack of fact-checking and due diligence from the press. Here we can bifurcate the end goal into two paths:

   1. Public fears and concerns may lead to changes in behavior or calls to action by government agencies. If people become fearful of non-nutritive sweeteners then regulatory agencies can be provided power and oversight into products and thus dictate what people can put into their bodies. Policies may be changed that may also reflect the growing public’s fears, even if those fears are based on false pretenses.

   2. Pharmaceutical manufacturers and researchers may then provide a treatment which may or may not work to resolve the disease in question. Regardless, millions to billions of dollars can be directed towards this research endeavor, with the end result being medicalization of many people who may not need the drug or may be taking a drug that has no clinical benefit with uncertain side effects.

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Apologies as I had a lot more to say regarding this situation, but in looking into some of the work being put out by Hazen’s team I couldn’t help but consider the extent to which this represents many of the issues people have with science.

Anyways, it’s all the more reason to remain vigilant, question and remain skeptical, and always do your own research.

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1. Bear in mind that these aren’t direct comments from readers, and instead is me examining the line of thinking in which results from these prior studies can create the perception that crackdowns should be occurring.