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Taking Care of Mental Health

AUTHOR: Daria Šurić, MPharm.

Supplementation with certain vitamins and supplements may offer potential benefits for mental health, such as managing symptoms of depression, anxiety, and stress-related conditions. However, it's crucial to emphasize that supplements are typically considered as complementary therapies and should be used under the guidance of healthcare professionals. Further research is needed to better understand their mechanisms and effectiveness in addressing mental health issues.

What is mental health?

According to the WHO definition: “Mental health is a state of mental well-being that enables people to cope with the stresses of life, realize their abilities, learn well and work well, and contribute to their community.”

It is an integral component of health and well-being that underpins our individual and collective abilities to make decisions, build relationships and shape the world we live in. Mental health is a basic human right. And it is crucial to personal, community and socio-economic development.

 

FIGURE 1:  Key facts regarding mental health according to WHO

Affordable, effective and feasible strategies exist to promote, protect and restore mental health.
The need for action on mental health is indisputable and urgent.
Mental health has intrinsic and instrumental value and is integral to our well-being.
Mental health is determined by a complex interplay of individual, social and structural stresses and vulnerabilities.

 

Mental health is more than the absence of mental disorders. It exists on a complex continuum, which is experienced differently from one person to the next, with varying degrees of difficulty and distress and potentially very different social and clinical outcomes.

Mental health conditions include mental disorders and psychosocial disabilities as well as other mental states associated with significant distress, impairment in functioning, or risk of self-harm. People with mental health conditions are more likely to experience lower levels of mental well-being, but this is not always or necessarily the case1.

 

Mental disorders prevalence

As the world comes to live with and learn from, the far-reaching effects of the COVID-19 pandemic, we must all reflect on one of its most striking aspects – the huge toll it has taken on people’s mental health. Rates of already-common conditions such as depression and anxiety increased by more than 25% in the first year of the pandemic, adding to the nearly one billion people already living with a mental disorder. Pre-pandemic, in 2019, an estimated 970 million people in the world were living with a mental disorder*.

Between 2000 and 2019, an estimated 25% more people were living with mental disorders, but since the world’s population has grown at approximately the same rate the (point) prevalence of mental disorders has remained steady, at around 13%.

Having good mental health means we are better able to connect, function, cope and thrive. Mental health exists on a complex continuum, with experiences ranging from an optimal state of well-being to debilitating states of great suffering and emotional pain2.

In both males and females, anxiety disorders and depressive disorders are the two most common mental disorders. Anxiety disorders become prevalent at an earlier age than depressive disorders, which are rare before ten years of age. They continue to become more common in later life, with the highest estimates in people between 50 and 69. Among adults, depressive disorders are the most prevalent of all mental disorders.

In 2019, 301 million people globally were living with anxiety disorders; and 280 million were living with depressive disorders (including both major depressive disorder and dysthymia). In 2020, these numbers rose significantly as a result of the COVID-19 pandemic. In both cases, the countries that were hit hardest by the pandemic had the greatest increases in disorder prevalence. All over the world, there was a greater increase in disorder prevalence among females than among males, probably because females were more likely to be affected by the social and economic consequences of the pandemic. And globally there was also a greater change in prevalence among younger age groups than older ones, potentially reflecting the deep impact of school closures and social restrictions on youth mental health.

 

Types of mental health disorders

Specific mental disorders are grouped together due to features they have in common. Some types of mental illness are as follows:

  • anxiety disorders
  • mood disorders, e.g. depression
  • schizophrenia disorders

 

Impact of stress and mental health

Everyone experiences stress from time to time. When it becomes chronic, it can affect mental health. When stress it’s long-lasting or chronic, it may begin to affect mental health.

WHO definition of stress:

“Stress can be defined as a state of worry or mental tension caused by a difficult situation. Stress is a natural human response that prompts us to address challenges and threats in our lives. Everyone experiences stress to some degree. The way we respond to stress, however, makes a big difference to our overall well-being.”

The body’s autonomic nervous system controls the heart rate, breathing, and other body processes that take place without conscious effort. It triggers the fight-or-flight response during stressful situations, causing an increased heart rate, dilated pupils, sweating and other symptoms.

Continued activation of this response can cause wear and tear on the body and result in physical and emotional symptoms. Emotional and mental symptoms of stress can include anxiety or irritability, depression, panic attacks and prolonged sadness.

 

Mental health and help from supplements

Mood improvement refers to a beneficial change in one’s temporary mental or emotional state which can include improvements in feelings of anxiety, anger, sadness, relief, positivity, optimism, loneliness, insecurity, happiness, excitement, curiosity, and calmness.

When “low mood” turns very severe or simply lasts too long, it is often classified as a mood disorder.

A growing body of research suggests that certain vitamins and supplements may help with various mental health issues, especially with anxiety and depression.

Before starting any supplement for mental health, it is important to consult a healthcare professional because concurrently taking a drug for mental health disorders and a dietary supplement could lead to adverse effects. They are just one part of an overall treatment plan for mental health issues.

It’s crucial to understand that although these supplements may provide relief for symptoms, they are usually regarded as complementary therapies.

Saffron (Crocus sativus L.)

Saffron is a spice derived from Crocus sativus L. and has traditionally been used as a food spice. It has gained scientific attention recently for its potential anti-depressant effects and is available in extract form as a dietary supplement.

A substantial body of evidence has been gathered, providing a strong basis for the assertion that saffron exhibits clear antidepressant effects, consistently surpassing the performance of placebos. Moreover, there is some indication that saffron may also possess anti-anxiety properties, taking into consideration that the supporting evidence in this regard is not as robust, and further research is necessary, especially in the context of specific anxiety disorders. Typically, clinical trials suggest that a standard dose of 30 mg daily of saffron extract is associated with minimal safety concerns, with no meaningful differences in adverse events compared to placebos. Saffron can be conveniently taken in supplement form, twice daily.

Taking 30 mg saffron extract daily (both petals and stigma) appears to be effective in reducing depression in persons with major depressive disorder, and the potency appears to be comparable to reference drugs (fluoxetine, citalopram, and imipramine). That’s not to say that the evidence is equivalent to those drugs, however. Other doses may also be effective but 30 mg of extract is the most common dose. Results of 31 studies done altogether on 1565 participants have shown moderate improvement in depression and a moderate decrease in depression symptoms which is a very promising result for supplement ingredients. Also, in 6 relevant studies targeting anxiety, symptoms decreased indicating a small improvement which is also a good result for a supplement.

 

Vitamin D’s connection with mental health

The aim of the meta-analysis done on Vitamin D deficiency and depressive symptoms was the identification and summary of studies examining the relationship between vitamin D levels and the risk of depression and depressive symptoms severity, published between January 2008 and January 2019.

Compared to the group with the highest vitamin D, the group with the lowest vitamin D group had 51% higher odds of depression, with negligible heterogeneity (differences in results due to differences in study methodologies) among the studies3.

Low levels of vitamin D have been associated with depression. The decrease in vitamin D production caused by reduced sunlight during the winter months may be a factor in seasonal affective disorder (SAD).

If vitamin D levels are not low, supplementation isn’t likely to benefit mood. If they are low, supplementation is more likely to help if a person is suffering from major depression.

 

Rhodiola (Rhodiola rosea)

Rhodiola rosea is a medicinal plant which has traditionally been used as an anti-fatigue agent and adaptogenic compound. The root contains a number of bioactive compounds, but the main two that are thought to mediate its effects are rosavin and salidroside. Rhodiola supplements are generally taken in the form of root powder or standardized extracts with 1–5% salidrosides. Although Rhodiola supplements are usually taken for their stress- and fatigue-reducing effects, they may also have antidepressant and antioxidant properties.

It is important to mention potential risks: interactions with other medicinal products and other forms of interaction: Rhodiola rosea may decrease the activity of CYP2C9. With simultaneous treatment, there is a risk of an increase in the plasma concentration of medicinal substances that are metabolized by CYP2C9 (e.g., warfarin and phenytoin). In case a drug is converted to its active metabolite via CYP2C9 (e.g., losartan) the effect may be decreased during simultaneous treatment with Rhodiola rosea4.

One sort of plant preparation was recorded in traditional use (Dry extract (DER 1.5-5:1), extraction solvent ethanol 67-70% (V/V)), the fixed dosage is: 144 to 200 mg in a single dose, 1 to 2 times per day; daily dose: 144 to 400 mg and the indications for traditional uses are defined: the relief of symptoms of stress, such as fatigue and exhaustion4.

Supplementation of Rhodiola rosea tends to refer to either the extract (standardized to 4 mg of salidroside (rhodioloside) per 144 mg tablet) or an equivalent extract.

Usage of Rhodiola as a daily preventative against fatigue has been reported to be effective in doses as low as 50 mg. Rhodiola has two on-hold EFSA health claims related to stress and the nervous system (Table 1.).

In Poland, legislation for food supplements has set limits:

Root powder < 216 mg is the recommended daily dose of the product,

Extract (ratio 1.5-5:1) < 144 mg of the recommended daily dose of the product,

Extract standardised for rosavins and/or salidrosides: not more than 15 mg of rosavins per recommended daily dose of the extract, not more than 5 mg of salidrosides per recommended daily dose of the extract. It is recommended that the following warning be included on the label for dietary supplements containing Rhodiola rosea L.: “Not to be used by children, pregnant and breastfeeding women.”

In Croatia, in food supplements maximum daily dose is 50 mg of root and root extract.

In the Czech Republic: Standardized root extract with 4% of rosavin: maximum of 100mg/day.

Acute usage of Rhodiola for fatigue and anti-stress has been noted to be taken in the 288-680 mg range in studies.

The anti-stress effects of Rhodiola may occur in part due to it being able to blunt cortisol release under stressful conditions5.

In a randomized, double-blind, placebo-controlled trial, 60 participants with stress-related fatigue were allocated to take 576 mg of Rhodiola extract daily, or placebo for 28 days.

There were small statistically significant improvements in burnout on the Pines scale. Salivary cortisol was somewhat reduced in the morning6.

Rhodiola rosea also has on-hold claims targeting stress, and sleep. (Table 1.)

 

TABLE 1: on-hold EFSA claims for Rhodiola rosea

13-1 ID Wording Conditions
2659 EFSA Access Database: EXTRACT, 20 drops are equal to 95 mg dry root of rhodiola.
Helps organism to adapt for emotional stress, physical effort./Helps to stimulate the nervous system./Has beneficial effect in fatigue and headaches induced by stress./Beneficial for the sleep difficulties, poor appetite, decline in work performance./Helps to stimulate perception, improve state of mind./Helps to support potency,has beneficial effect on cardiovascular system because it helps to protect against stress and hypertension.
2829 EFSA Access Database: Extract: 30 mg./Used as part of a multibotanical product
As a natural antioxidant it helps strengthen the body against the harmful effects of external environment./Has antioxidant properties/helps reduce the negative impact of stress/helps protect the nervous system from the damage caused by free radicals./Helps reduce the negative impact of stress on the body./Promotes physical and mental resistance.

 

Zinc

The potential benefits of supplementation with zinc are largely dependent on the individual’s zinc status. Therefore, supplementation with zinc is unlikely to provide a benefit if zinc levels are already adequate and the person is not zinc deficient.

Multiple studies have explored the association between zinc deficiency and depression. Zinc deficiency is known to impair neurotransmitter function, particularly serotonin, which is closely linked to mood regulation. Furthermore, it may lead to neuroinflammatory processes, oxidative stress, and alterations in the hypothalamic-pituitary-adrenal (HPA) axis, all of which are implicated in depression. However, it is important to note that causation is not yet firmly established, and additional research is needed to delineate the exact mechanisms underlying this relationship.

The reduction in depression is notable only for treatment-resistant depression alongside a pharmaceutical antidepressant; there does not appear to be a benefit to persons who respond to antidepressants and the inherent anti-depressant effects without a pharmaceutical add-on are modest at best7.

it is important for healthcare providers to consider zinc status when evaluating patients with depressive symptoms, as addressing any underlying deficiencies may be a worthwhile component of a comprehensive treatment plan for depression.

Magnesium

Magnesium, an essential mineral, plays a crucial role in various physiological processes, and there is a growing body of scientific research exploring the relationship between magnesium levels and stress.

Stress can lead to the depletion of magnesium stores in the body. This depletion may occur due to several mechanisms, including increased urinary excretion of magnesium and altered cellular uptake. Reduced magnesium levels can, in turn, have far-reaching consequences for both the physiological and psychological aspects of stress.

A double-blind randomized clinical trial was conducted on 46 depressed subjects. The participants were randomly allocated into the magnesium (MG) and the placebo (PG) group and received 500 mg of magnesium and placebo daily for 8 weeks. Beck’s test was conducted and blood samples were taken at baseline and after the intervention period for analysis of serum magnesium and BDNF. Daily intake of 500 mg magnesium oxide for at least 8 weeks improved Beck’s test score and serum magnesium in depressed patients but had no significant effect on BDNF levels between the two groups. Further research is recommended9.

 

S-Adenosylmethionine (SAMe)

S-Adenosylmethionine (SAMe) is a biochemical compound consisting of methionine linked to an adenosine triphosphate (ATP) molecule. SAMe naturally circulates in the bloodstream and serves as a methyl donor. In chemistry, a methyl group is essentially a carbon atom bonded to hydrogen atoms, and the act of donating this methyl group to other molecules plays a vital role in expediting or maintaining various metabolic processes within the body. Certain physiological conditions are linked to reduced levels of SAMe in the circulatory system, such as osteoarthritis and depression, where SAMe exhibits significant therapeutic potential.

Following an initial accumulation period lasting 1 to 2 months, the administration of supplemental SAMe at daily doses ranging from 800 to 1600 milligrams demonstrates efficacy comparable to certain pharmaceutical treatments for both osteoarthritis and depression. Furthermore, SAMe appears to enhance the effects of some antidepressant medications.

In conclusion, the results of the present study, which is the first randomized, double-blind, placebo-controlled trial of SAMe augmentation to be conducted in this patient population, provide preliminary evidence suggesting that SAMe can be an effective, relatively well-tolerated, and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder. Further studies are required to confirm whether oral SAMe should be added to the antidepressant treatment armamentarium10.

There are some challenges associated with SAMe:

  • Production and Stability: SAMe is a sensitive molecule that can degrade under various conditions. One challenge is to develop stable formulations and production methods to ensure the purity and longevity of SAMe supplements.
  • Bioavailability: SAMe’s bioavailability is a concern, as it is poorly absorbed when taken orally. Formulating SAMe to improve its absorption and efficacy is a significant challenge.

 

  • Dosing: Determining the appropriate dosing regimen for SAMe supplements can be challenging, as the optimal dosage may vary for different individuals and conditions. Achieving a balance between therapeutic effectiveness and avoiding potential side effects is crucial.

SAMe is an ingredient with great potential, but still, there are some uncertainties to be cleared.

 

L-theanine

L-theanine is a non-protein amino acid derived most commonly from tea (Camellia sinensis) leaves, which may be beneficial in the treatment of anxiety and sleep disturbance as suggested by preliminary evidence.

L-theanine, an amino acid contained in green tea leaves, is known to block the binding of L-glutamic acid to glutamate receptors in the brain and has been considered to cause anti-stress effects by inhibiting cortical neuron excitation. Both L-theanine and caffeine, which green tea contains, have been highlighted for their beneficial effects on cognition and mood.

The results after the mental tasks showed that L-theanine significantly inhibited the blood-pressure increases in a high-response group, which consisted of participants whose blood pressure increased more than average by a performance of a mental task after placebo intake. Caffeine tended to have a similar but smaller inhibition of the blood pressure increases caused by mental tasks. The result of the Profile of Mood States after the mental tasks also showed that L-theanine reduced the Tension-Anxiety scores as compared with placebo intake10.

Conclusions of the study findings denote that L-theanine reduces anxiety and attenuates the blood pressure increase in high-stress-response adults.

In humans, L-theanine has been reported to modulate alpha activity and play a role in attentional tasks in electroencephalogram studies, as well as provide beneficial effects on mental state, including sleep quality. To our knowledge, however, only its acute effects have been investigated in healthy individuals. The anti-stress effects of L-theanine (200 mg/day) have been observed following once- and twice-daily administration, while its attention-improving effects have been observed in response to treatment of 100 mg/day on four separate days and 200 mg/day single administration, which was further supported by decreased responses in functional magnetic resonance imaging. Moreover, L-theanine has been suggested to have potential therapeutic effects in psychiatric disorders. In accordance with this, we have reported multiple favourable effects of four weeks of L-theanine administration (250 mg/day) in patients with major depressive disorder (MDD), although this was an open-label study. Stress-related symptom (i.e., depression, anxiety-trait, and sleep) scores decreased and cognitive function (i.e., verbal fluency and executive function) scores improved after four weeks of L-theanine administration. The reduction in sleep quality problems (disturbances in sleep latency, sleep disturbance, and use of sleep medication) was greater in the L-theanine administration compared to the placebo administration, while verbal fluency, especially letter fluency, was improved in the L-theanine administration among individuals who showed relatively low performance at pretreatment. Moreover, L-theanine administration was safe and well complied with. Therefore, L-theanine may be a suitable nutraceutical ingredient for improving mental conditions in a healthy population12.

 

 

*This estimate includes people living with schizophrenia, depressive disorders (including dysthymia), anxiety disorders, bipolar disorder, autism spectrum disorders, attention-deficit/hyperactivity disorder, conduct disorder, idiopathic developmental intellectual disability, eating disorders and other mental disorders, as covered in the GBD 201

References:

  • 1 https://www.who.int/news-room/fact-sheets/detail/mental-health-strengthening-our-response
    2 WHO Mental health report: https://iris.who.int/bitstream/handle/10665/356119/9789240049338-eng.pdf?isAllowed=y&sequence=1
    3 Wilczyński KM, Chęcińska K, Kulczyk K, Janas-Kozik M. Vitamin D deficiency and depressive symptoms: meta-analysis of studies . Witamina D i objawy depresji: meta-analiza badań. Psychiatr Pol. 2022;56(6):1327-1344. doi:10.12740/PP/OnlineFirst/130992
    4 https://www.ema.europa.eu/en/documents/herbal-monograph/draft-european-union-herbal-monograph-rhodiola-rosea-l-rhizoma-et-radix-revision-1_mo.pdf
    5 Panossian A, Hambardzumyan M, Hovhanissyan A, Wikman G. The adaptogens rhodiola and schizandra modify the response to immobilization stress in rabbits by suppressing the increase of phosphorylated stress-activated protein kinase, nitric oxide and cortisol. Drug Target Insights. 2007;2:39-54.
    6 Olsson EM, von Schéele B, Panossian AG. A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue. Planta Med. 2009;75(2):105-112. doi:10.1055/s-0028-1088346
    7 Ranjbar E, Shams J, Sabetkasaei M, et al. Effects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression. Nutr Neurosci. 2014;17(2):65-71. doi:10.1179/1476830513Y.0000000066
    8 Siwek M, Dudek D, Paul IA, et al. Zinc supplementation augments efficacy of imipramine in treatment resistant patients: a double blind, placebo-controlled study. J Affect Disord. 2009;118(1-3):187-195. doi:10.1016/j.jad.2009.02.014
    9 Afsharfar M, Shahraki M, Shakiba M, Asbaghi O, Dashipour A. The effects of magnesium supplementation on serum level of brain derived neurotrophic factor (BDNF) and depression status in patients with depression. Clin Nutr ESPEN. 2021;42:381-386. doi:10.1016/j.clnesp.2020.12.022
    10 Papakostas GI, Mischoulon D, Shyu I, Alpert JE, Fava M. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial. Am J Psychiatry. 2010;167(8):942-948. doi:10.1176/appi.ajp.2009.09081198
    11 Yoto A, Motoki M, Murao S, Yokogoshi H. Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses. J Physiol Anthropol. 2012;31(1):28. Published 2012 Oct 29. doi:10.1186/1880-6805-31-28
    12 Hidese S, Ogawa S, Ota M, et al. Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial. Nutrients. 2019;11(10):2362. Published 2019 Oct 3. doi:10.3390/nu11102362
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