Integrative nutrient therapies for depression: biochemical remedies to melancholy

   Written by Justin G Maguire., 13 May 2020

Let’s quickly paint a little picture. It’s a normal weekday, let’s say Wednesday. You get up, get dressed, get breakfast, get in your car, and get to work. Nothing strange really. Everything is happening as it should, but why doesn’t it feel like it usually does? You go through the workday, go to the car, go get groceries, go home, go, cook, go shower, and go to bed. Again, everything happens as it should, but you feel gloomy. You turn off the light and tell yourself to try again tomorrow. Then it happens again the next day.
Maybe it’s time for a pick me up. You message a friend and arrange something fun for Saturday. You power through Friday just to make tomorrow come a bit faster. You and your friend go out, have a good time, and you take on the week with new motivation. Yet, when Monday comes, it feels off again. Must be the Monday Blues, but Tuesday is the same. Wednesday is the same, and Thursday is the same. It hangs over you like a dark raincloud that just won’t drop.
Depression is a mood disorder that involves a persistent feeling of sadness, loss of interest, lowered or increased appetite, and generally a loss of motivation in life. We all go through depressing moments in our life, however, if you experience a depressed mood persisting for longer than two weeks at a time, then you may be facing the challenge of dealing with depression.
Traumatic events, genetics, and immunological compromise can all trigger depression. Regardless of the cause, treatment needs to be more targeted and specialized in supporting depression.
Depression Stats
Approximately three hundred million people in the world suffer from depression (World Health Organization., Feb 2017) with little sign of decreasing (Ledford, 2014; Gerhard et al., 2016). Since 1950, suicide rates have increased from approx. 16% to 30% globally (Burns P T, 2020), as such depression is no longer a rare topic of discussion, but rather, depression has become part of our global consciousness.

Types of depression
There are two major classes of depressive disorders, namely:
Major depressive disorder: ranging from mild to severe; major depressive disorders involve loss of interest, decreased energy and lack of motivation and in extreme cases suicidal tendencies.   Dysthymia: In contrast dysthymia is a form of depression in which symptoms are not as extreme as major depressive disorder, however, symptoms appear to be more persistent, lasting a longer period of time.  
Treating depression conventionally involves initial psychotherapy and in certain cases the use of serotonin and / or dopamine reuptake inhibitors (Mayo Clinic., 2020), yet what many practitioners are forgetting is considering the methylated response a person may have to a specific drug. Most antidepressants come with a warning label, stating that the drug may cause suicide; why then are certain people more vulnerable to unwanted reactions to psychiatric drugs than others? The answer may possibly be found within the nutrient status of depressed persons!
Methylation, genetic and Heme status within depression 
Methylation, Acetylation and Sulfation all play vital roles in neurochemistry. In specific cases of depression, one may be under or over methylated, dramatically influencing the effect of an anti-depressant medication prescribed (Walsch W., June 2012), additionally, genetics also play a role in determining nutrient needs toward establishing optimal neurotransmitter production (Lynch B., 2018).
Prescription of SSRIs (selective serotonin reuptake inhibitors) within those who express over methylated status can lead to an increase of depressive symptoms, in certain cases even triggering suicidal attempts.  In contrast, prescription of anti-anxiolytic drugs to those who are undermethylated may worsen symptoms, leading to a decrease in dopamine activity and overall motivation in life. Thus, understanding one’s methylation status is of the utmost importance when prescribing or supporting the prescription of anti-depressant medication.
Additionally, the activity of two genes respectively named: MAO (Monoamine oxidase A) and COMT (Catechol-O-methyltransferase) both play a role in the oxidation and breakdown of neurotransmitters, as such considerations to either fast or slow genetic activity alter the requirement of nutrient precursors to maintain equilibrium between production and detoxification.
Whilst nutrient and genetic status is of high importance a common variable often seen throughout depressives is a lack in the ability to reduce oxidised glutathione into its available and powerful antioxidant form (Godlewska B R, et al., 2014). Contributing factors to poor glutathione production and recycling often stem from impaired Heme metabolism, cited by pyrrole disorders (Warren B, et al., 2021).
Pyrrole disorder can be inherent or acquired through environmental triggers such as excessive heavy metal exposure, leading to an increase of beta-amyloid plague and other pro-inflammatory proteins in the brain, further exacerbating depressive symptoms. Incorporating targeted nutrient therapy enables improved innate ability not only to produce glutathione but also to balance mineral and vitamin profiles in a way which reduces oxidative stress and maximises the use of amino acids required to produce neurotransmitters, supporting brain chemistry and saving lives from depression.
Immunity, cortisol and depression 
The onset of depression is multifactorial, incorporating the totality of biochemical actions and reactions. Notably, the state of our immunity plays a huge role in how our brain is able to produce healthy neurochemistry or proinflammatory enzymes. IDO (indoleamine 2, 3- dioxygenase) activity is one major player which influences the use of amino acids, shifting function from the production of neurotransmitters to neuroinflammatory dicarboxylic acids such as quinolinic acid (Hestad K. A et al., 2017).
Triggers such as gram-negative bacterial overgrowth, candida and clostridia all have the ability to instigate heightened IDO activity and thus leading one into a state of neurochemical depression. Furthermore, an increase in cortisol reactive stressors, such as excessive artificial blue light, psychological distress etc… increases the release of TDO (tryptophan 2, 3 dioxygenase) which also creates a ‘steal’ of amino acids, redirecting their use toward proinflammatory outcomes to fuel the needs of the immune system.
Efforts toward modulating cortisol function may prove beneficial toward redirecting one’s raw material toward producing the neurotransmitters lacking in cases of depression (Gibney M S et al., 2014). Additionally, determining whether indeed microorganisms such as candida are compromising your amino acid utility, would provide a valuable strategy targeted toward re-establishing the neurochemical directive of amino acid use toward neurotransmitter production.
Nutrition recommendations and depression 
There is a strong relationship between irritable bowel syndrome and depression (Khatri M., 2022), as such, dietary advocation of nutrition intake to support optimal microflora whilst also minimising immunological reaction would prove to be beneficial. The GAPS (gut and psychology syndrome) diet aims to re-establish optimal immunological defence by improving the integrity of tight junctions within the gut lining in addition to restoring optimal microbiome balance and diversity (Richter A., 2020).
The GAPS diet includes the following considerations:
  Excluding the intake of grains, pasteurized dairy, di and polysaccharides consuming therapeutic strength probiotics, digestive enzymes, essential fatty acids and a multimineral/vitamin supplement  

Peptides and Depression 
New advancements have recently been made within the field of molecular medicine, incorporating the use of target-specific peptides to combat depression. GLP 1 (Glucagon-like peptide 1) and SELANK are two commonly used peptides in the fight again depression. Although peptides are far safer to use than pharmaceutical drugs, taking into consideration the full aetiology of depression is vital in developing a synergistic intervention protocol, one which will support not exacerbate symptoms.
GLP 1 has been shown to improve states of neuroinflammation, synaptic function and neurotransmitter balance (Young-Kook K, et al., 2020) thereby reducing depletion of glutathione stores and an associated rise in neurodegeneration. Given that most depressants express poor recycling of glutathione, in cases whereby depression may be accompanied by metabolic syndrome in relation to poor glucose control, GLP1 may prove to be useful. 
SELANK is a gastric peptide derivative that has had an extra 3-part amino acid series added to its chain to increase stability for exogenous use. SELANK is not only anti-anxiolytic but also anti-viral in nature, thus those who are suffering from depression linked to immunological or persistent environmental infections (candida etc…) may do well to incorporate SELANK into a depressive intervention protocol. Additionally, those who are on prescriptive diazepam use may benefit from the co-administration of both SELANK and diazepam, as studies have shown SELANK to improve the efficacy of benzodiazepines (Kasian A, et al., 2017) thus lowering the quantity needed to modulate stress often associated with depression.
Recommended testing and depression
Within the realm of alternative therapy, one can often become deluded as to what to do toward helping themselves or a loved one. Opting to invest in targeted molecular diagnostics proves to take out the guesswork and enables a targeted and quantifiable approach to healing depression. Here are my top picks of both functional diagnostics and blood chemistry markers in assessing the Integrative medical needs of depressed patients
  whole blood histamine full Thyroid panel (including rT3) full liver function panel RBC zinc Serum copper Ceruloplasmin RBC folate Methylmalonic acid Organic Acids urinalysis Dried hormone urinalysis Hair mineral analysis  

The material contained within this article is not intended to replace the services and/or medical advice of a licensed health care practitioner, nor is it meant to encourage diagnosis and treatment of disease. It is for health education purposes only based on the clinical experiences of its authors. Autonomic Coaching Pty Ltd. Justin Maguire or any of its associates and members do not accept legal responsibility for any problems arising from your personal experimentation with the health education information described herein. Any application of suggestions set forth in the following portions of the article is at the reader’s discretion and sole risk.  You are solely responsible for implementing treatment strategies for your or others’ health. Implementation or experimentation with any supplements, herbs, dietary changes, medications, and/or lifestyle changes, etc., discussed in this article, is done so at your sole risk. As an individual, you accept full responsibility for using/implementing any health education information discussed in this article and understand that experimentation with supplements, medications, herbs, dietary changes, etc. needs to be discussed with your personal physician first.
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