A very tepid positive take on the use of EPA in major depression

In a study by Rapaport et al., on the use of EPA in major depression there is this sentence in the abstract, ‘While overall treatment group differences were negligible (ES=−0.13 to +0.04), subjects with any “high” inflammation improved more on EPA than placebo…’ That is a very tepid positive take.

EPA enteric coated softgels do not work. EPA + DHA softgels must be bitten, the contents swallowed and then softgel capsules thrown away for EPA + DHA to work against major depression

ProEPAxtra was the EPA product used in the Rapoport study. Here is an ad for ProEPAxtra on Amazon. The ad does not explicitly state that the softgel is enteric coated, however, the ad states ‘no fishy aftertaste’ and ‘better absorbed’ both of which are warnings than the soft gel could have some sort of enteric coat. Enteric coated fish oil soft gel capsules appear to be frosty or dull. The softgels in the ad appear to be dull in appearance. The quality of the fish oils themselves is not being questioned.

Gut microbiota and mental illness

I have been arguing on this blog that supplements have to be available in the gastrointestinal tract as well as systematically for supplements to be helpful. There has been a growing realization that what happens in the gut can have a huge impact on mental health. See these reviews Microbes and mental health: A review; Harnessing Gut Microbes for Mental Health: Getting From Here to There and Brain-Gut-Microbiota Axis and Mental Health.

If supplements are not available in the gastrointestinal tract this cannot but affect gut microbiota differently compared to supplements that are available in the gastrointestinal tract. I am open to the possibility that differences in gut microbiota can play a big role in mental states, however, the gut could also be set up so the gut has to use nutrients when nutients first pass through the gut. Use of nutrients by the gut could be a necessary first step in the use of nutrients systematically.

There is a lot of talk about how the diet of our very distant ancestors is the diet that is appropriate for us. One thing is certain about the diet of our very distant ancestors. Our very distant ancestors did not take nutrients than were formulated not to be available in the gut.

Only taking supplements that are available in the gut, when taking supplements, is one way to address to address gut microbiota positively. As an example EPA + DHA combinations are frequently supplied in enteric coated softgels to avoid ‘fishy smells’. However, biting on the softgels, swallowing the contents and then throwing the softgels away works much better for depression. And what is more even given EPA + DHA work in clinical trials EPA + DHA will not work in the field as EPA + DHA supplements sold in stores are very frequently enteric coated.

Bone mineral density and major depression

Decreased bone mineral density is associated with major depression. There are also low vitamin D levels in individuals who are depressed. Ahedonia in major depression could be due to hidden osteomalicias. Taurine, vitamin D and vitamin K could treat hidden osteomalacias present in major depression. Supplements used to treat hidden osteomalicias, would not be effective for intense sadnesses that frequently occur with major depressions.

Major depressive disorder and taurine

Ketamine is being used in the treatment of major depressive disorder. Ketamine is a glutamate NMDA receptor antagonist. A ‘modulating ‘effect of ketamine on NMDA receptors has been stated as giving rise an antidepressant effect of ketamine in major depressive disorder.

Glutamate toxicity due to calcium influx through L-, P/Q-, N-type voltage-gated calcium channels and NMDA receptor calcium channels is inhibited by taurine with taurine having a neuroprotective effect. The treatment presented on the Bipolar Depression page, which includes taurine, would address glutamatergic neurotransmission and could be effective for major depressive disorder.

Addressing glutamatergic neurotransmission via taurine is much preferable to addressing glutamatergic neurotransmission via ketamine. Research points to supplemental taurine as reducing homocysteine levels (Ahn, 2009), reducing cholesterol levels in animals (Guo et al., 2017; Chen et al., 2012) having an anti-obesity effect, as being negatively associated with ischemic heart disease, as ameliorating diabetes and points to taurine deficiencies as resulting in premature aging. Research on rats points to the neurotoxic effects of repeated ketamine exposure as being due to changes in purine metabolism and glycerophospholipid metabolism in the prefrontal cortex that persist even after ketamine withdrawal.