Psychiatry is Broadening the Biological Paradigm at Last – A Commentary on Hoffmann et al. “Dietary Supplements in Psychiatric Treatment – A Narrative Review”

Those clinicians I have met during my academic career were mostly pragmatically interested in the well-being of patients. And so it is not surprising that alongside, or even in addition to mainstream theorizing and therapy, complementary approaches and unconventional therapeutic avenues have been used all along. The review of Hoffmann and colleagues giving an overview over such approaches using various supplements is a testimony to this pragmatic stance [1]. And there is some theoretical background music to it that could be played to support their case. After all, it has long been known that there is an epidemiological north-south gradient of various neurological diseases, especially multiple-sclerosis [2], that makes plausible that vitamin D should and could play a role in the genesis of neurological, and, why not, psychiatric diseases that often have an inflammatory and immunological component to it [3]. It is no surprise, therefore, that studies regarding vitamin D are most frequently mentioned in the review. If, as some suggest, there are genetically fixed vitamin D receptor deficiencies in the population [4] [5], it is to be expected that most people have no problems with reduced vitamin D levels through a lack of direct sunlight exposure, but that some very vulnerable persons do have problems as a consequence. If this is so, normal dosages would be too low, and perhaps more daring approaches are needed?

Ruding suggested in the 80ies that some psychiatric diseases are actually due to a malfunctioning of lipid-metabolism, be it because the supply with essential fatty acids has changed, or be it because of individual, idiosyncratic metabolic problems [6]. That is not surprising, given the fact that the neuronal system depends crucially on lipids, especially on phospholipids that make up the membranes and are necessary for axonal growth and dendritic sprouting [7] [8]. Iain McGilchrist has pointed out in his magisterial “The Master and His Emissary”, where he traces the development of our modern mindset to a loss of balance between left- and right-brain style mental activity [9], that schizophrenia was apparently unknown before the industrial revolution [10]. Whether the epidemiological evidence for this statement is strong enough I do not know. But I find it quite intriguing to observe that the nutritional balance between omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) has long been 1:1, up until the middle of the 19^th century, when two things happened rather simultaneously [11] [12] [13]. Due to the possibility of industrial food production seeds containing mainly omega-6 PUFAs, such as corn, soy, sunflower, peanuts were grown at large scale, and the ratio between omega 3 and 6 PUFAs today is between 1:15 to 1:20 and can go up as high as 1:40 in children with behavioral and neurodevelopmental problems. The second change was the introduction of trans-fatty acids for margarine production and production of industrially produced fats for the food industry [14] [15] [16]. Omega-3 and omega-6 PUFAs have, physiologically speaking nearly opposite effects – omega-3 PUFAs are the precursors for all anti-inflammatory cytokines and omega-6 PUFAs are the precursors for pro-inflammatory cytokines [17]. And their balance is needed for optimal membrane fluidity and neuronal growth. But they share a long enzymatic pathway of converting enzymes. Thus, a shift of balance in the precursor products from 1:1 to 1:15 or 1:20 on a population basis, is a massive threat to public health in terms of favouring a proinflammatory state in a large part of the population. Hence, it is no surprise that in psychiatric patients this might come to the fore, because such patients are very likely those among the population that are most sensitive to such shifts or may have a genetic make-up that makes them vulnerable. If this is so, then we should anticipate that a long-term exposure to such a dysbalance in essential PUFAs might trigger a critical state, and then only long term-reversal with high dosages would be able to act therapeutically. This has been actually shown in recent meta-analyses of therapeutic trials, which are surely only the beginning [18] [19] [20] [21]. They do, however, point the way: in some patients, and perhaps we have to figure out first which ones they are, such nutritional interventions may actually be causal.

The second shift, towards more trans-fatty acids, may be central for the rise in incidence of coronary artery disease. This has, however, triggered mainly a canvassing of the population with lipid-lowering drugs whose main side-effects are muscle pain due to the depletion of co-enzyme Q10 [14] [22]. Hence it is logical that Q10 supplements are popular. Perhaps a review of the distribution of lipidlowering drugs would be more efficient and a causal treatment for widespread muscle pain?

These few hints might serve its purpose: nutritional interventions and supplements might be much more than just the odd add-on treatment. They might in fact point the way to more deeply located root-problems in certain types of patients. Perhaps we need to understand more about the differential metabolisms for fat, essential agents such as vitamins, before we can actually understand why and for whom such interventions are beneficial. Meanwhile, the data provided by the review hopefully lower the threshold for funders and researchers to really embark on well planned and thoughtful studies on such interventions. They will likely need to target the right types of patients with sufficiently powerful doses over a long enough period of time. This might in the end lead to a better understanding not only of therapy, but also to causes of psychiatriy diseases, at least for some patients.

• References

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