The Science Behind the Supplements
These studies are provided to assist you in determining the health benefits of certain supplements. Both research studies and clinical trials are conducted based upon a specific study design. The design will specify a given protocol that includes administration of a given form of the supplement(s), its concentration, the amount to be administered and the frequency of supplementation. The study design may include diet restrictions and may incorporate exercise. The study may include participants based on gender, ethnicity, medical conditions, or age. These factors should be considered when interpreting study findings.
OMEGA 3 FATTY ACIDS
A study conducted on 126 adults at risk for Type 2 diabetes of the First Nations population in British Columbia found that participants who consumed more omega-3 fatty acids exhibited significantly lower levels of insulin resistance compared to those with higher saturated fatty acid intake and were therefore, at greater risk for diabetes (Paquet 2013). Similarly, a 2011 study demonstrated a similar result among participants who ingested one gram of either a placebo or concentrated omega-3 fatty acids three times a day with meals over the course of six months. Lower levels of insulin resistance are known to correlate with reduced risks for metabolic syndrome and diabetes (Derosa 2011).
A 2010 study demonstrated that administration of supplemental fish oil significantly increased lean mass and significantly reduced fat mass in healthy adults (Noreen 2010). These finding are in agreement with a previous study that observed a significant reduction in fat mass following three weeks of increased consumption of fish oil (Couet 1997).
A six-week study in which participants were given supplemental fish oil led to a reduction in salivary cortisol, the hormone linked to increased abdominal fat. Reduced cortisol levels were found to significantly correlate with increased lean mass and decreased fat mass (Noreen 2010). Since higher salivary cortisol levels are associated with higher mortality rates, the reduction in salivary cortisol levels observed following fish oil supplementation likely has significant implications beyond positive changes in body composition (Schoorlemmer 2009).
Fish oil (omega 3 fatty acids) has been shown to increase fatty acid oxidation in humans and is known to inhibit hepatic fat lipogenesis (fatty acid synthesis). These processes shift the balance of fatty acid metabolism towards oxidation rather than fat storage (Couet 1997).
EPA and DHA were shown to prevent excessive adiposity and insulin resistance in rodents. Mechanistically, this is related to the ability of these fatty acids to increase hepatic, skeletal muscle, and adipose tissue fatty acid oxidation and their ability to reduce lipogenesis (Nishan 2011).
Inuit Eskimos, who receive high amounts of omega-3 fatty acids from eating fatty fish tend to have increased HDL cholesterol and decreased triglycerides. Several studies have shown that fish oil supplements reduce triglyceride levels (Dewailley 2001).
The role of omega-3 fatty acids in cardiovascular disease is well established. Studies indicate that one of the best ways to help prevent heart disease is to consume a diet low in saturated fat and rich in monounsaturated and polyunsaturated fats including omega-3 fatty acids. Clinical evidence suggests that EPA and DHA found in fish oil help to reduce risk factors for heart disease, including high cholesterol and high blood pressure. Fish oil has been shown to lower triglycerides, thereby lowering the risk of death, heart attack, stroke, and abnormal heart rhythms in people who have already had a heart attack. Fish oil also appears to help prevent and treat atherosclerosis by slowing the development of plaque and blood clots (Lee 2009).
A 2006 landmark study found that the Western diet is dramatically deficient in omega-3 fatty acids. This study established that 3.5g of omega-3 fatty acids are required per day to achieve the low rates of heart disease, stroke, depression, homicide, and bipolar disorder observed in Japan, where fish represents a predominant source of fat intake (Hibbelin 2006).
Investigators conducted a 12 week, double-blind, placebo-controlled and randomized clinical trial in which 68 medical students were given either 2.5g/day of omega-3 polyunsaturated fatty acids (PUFAs) or placebo capsules containing the fatty acid profile of a typical American diet. Students receiving the omega-3 fatty acid capsules showed a 20% reduction in anxiety compared to the placebo group. The reduction in anxiety symptoms associated with omega-3 fatty acid supplementation provides the first evidence that omega-3 fatty acids may have potential anti-anxiety benefits for individuals without an anxiety disorder diagnosis (Kiecolt-Glaser 2011).
The typical Western diet contains a significantly high ratio of inflammatory omega-6 fatty acids to anti-inflammatory omega-3 fatty acids. Omega-3 fatty acids have been shown to have a variety of health benefits including enhanced mood and reduced anxiety (Perica 2001; Hibbelin 2006; Appleton 2008). Many practitioners now recommend that the Omega-6 to Omega-3 ratio be kept below 4:1.
In a 2008 double-blind, placebo-controlled study, omega-3 fatty acid supplementation was given to participants experiencing substance abuse based upon the premise that low levels of omega-3 fatty acids play a role in the pathophysiology of some psychiatric disorders. The possibility of supplementation with omega-3 fatty acids to decrease anger levels was explored in a randomized 3-month trial. An anger scale was administered at baseline and each month thereafter. Those participants receiving omega-3 fatty acid supplementation experienced reduced anxiety, anger and aggression compared to the placebo group (Buydens-Branchey 2008).
A meta-analysis was conducted to evaluate the hypothesis that eicosapentaenoic acid (EPA) is the effective component in omega-3 fatty acid treatment of major depressive episodes. The search yielded 15 trials involving 916 participants. Studies were included if they had a prospective, randomized, double-blinded, placebo-controlled study design; if depressive episode was the primary complaint; if omega-3 fatty acid supplements were administered; and if appropriate outcome measures were used to assess depressed mood. The clinical outcome of interest was the standardized mean difference in the change from baseline to endpoint scores on a depression rating scale in participants taking the supplements compared to the placebo group. Investigators concluded that supplements containing EPA ≥ 60% of total EPA + DHA, in a dose range of 200 to 2,200 mg/d of EPA in excess of DHA, were effective against depression (Sublette 2011).
Japanese researchers studied the effects of L-theanine on psychological and physiological stress responses in a study that presented participants with a mental arithmetic task on four separate occasions with the intent to induce “math anxiety.” Participants receiving supplementation took L-theanine at the beginning of the test or halfway through the test. This short-term use of L-theanine had significant effects on manifestations of anxiety. Participants receiving supplementation experienced a reduction in heart rate compared with those receiving placebo. Analysis of heart-rate variability suggested that L-theanine modulated activation of the sympathetic nervous system that produces the “fight-or-flight” response. The ability to alter this system may help avert the deleterious long-term health consequences of stress (Kimura 2007).
In a 2004 double blind, controlled cross over study, researchers compared L-theanine with alprazolam (Xanax®), a commonly prescribed anti-anxiety drug. Sixteen healthy volunteers took 1 mg alprazolam, 200 mg theanine, or a placebo on separate occasions and each participant was tested with all three treatments. Following each dose, investigators obtained behavioral measures of anxiety in each participant before and after an artificially created state of anxiety. Only L-theanine effectively induced relaxing effects that were evident at the initial measurement of whether a person felt calm or anxious. The results are significant when the dose of alprazolam is taken into consideration since 1 mg is considered a high dose. Typically, doses of 0.25 to 0.5 mg of alprazolam are prescribed (Lu 2004).
A double-blind, randomized, placebo-controlled study was conducted based upon L-theanine’s neuroprotective, mood-enhancing, and relaxation properties. It was a first study designed to evaluate the efficacy and tolerability of L-theanine augmentation in antipsychotic treatment of patients with chronic schizophrenia and schizoaffective disorder. A dose of 400 mg L-theanine was added to the ongoing antipsychotic treatment. Forty participants completed the study protocol. Compared with placebo, L-theanine augmentation was shown to diminish anxiety symptoms in schizophrenia and schizoaffective disorder patients. General functioning, side effects, and quality of life measures were not affected by L-theanine augmentation. L-theanine was found to be safe and well tolerated (Ritsner 2011).
L-theanine has been historically reported as a relaxing agent, prompting scientific research on its pharmacology. Animal neurochemistry studies suggest that L-theanine increases brain serotonin, dopamine, and GABA. GABA is considered to be the brain’s own tranquilizer. It helps to reduce excess adrenalin and controls the levels of noradrenalin, dopamine, and serotonin. Insufficient levels of GABA are associated with anxiety, tension, depression, and insomnia. L-theanine increases the secretion of GABA thus helping the brain to calm itself. L-theanine displays a neuropharmacology suggestive of a possible neuroprotective and cognitive enhancing agent (Nathan 2006).
L-theanine is proposed to act as a glutamate antagonist offsetting the harmful effects of glucocorticoids (stress hormones) that disrupt serotonin, dopamine, and other brain chemicals. Glucocorticoids disrupt brain chemistry and affect mood and memory. L-theanine blocks certain signals produced by glutamate and suppresses harmful effects of glucocorticoids helping to restore chemical balance in the brain. Studies in animals indicate that L-theanine may also have protective effects for the brain. L-theanine seems to protect the body from excess glutamate which can be toxic to nerve tissue if levels are not regulated. L-Theanine shows some protective effects on nerve cells when there is decreased blood flow. Protection of brain cells could play an important role in illnesses that cause anxiety, such as Alzheimer’s disease (Kakuda 2000; Nathan 2006).
In 2004, Japanese researchers investigated the components of green tea to determine how catechins, theanine, caffeine, and green tea powder affected weight gain in female mice. Researchers found that each of the components suppressed weight gain; however, green tea powder, catechins, and theanine also reduced triglyceride levels. The team concluded that L-theanine may prevent weight gain and fat accumulation (Zheng 2004).
A 2011 review article (Vuong 2011) discussed the benefits of L-theanine to promote weight loss in addition to boosting immune function, providing cardiovascular protection, and improving concentration and learning ability.
Studies using animal models have shown that supplementation with Rhodiola rosea promotes the breakdown of triglycerides and the reduction of perilipin proteins to speed up fat metabolism.Rhodiola rosea also plays a role in balancing the stress response that in turn regulates fat metabolism via the hypothalamic-pituitary-adrenal axis. Under chronic stress, the hypothalamic-pituitary-adrenal axis may function poorly to disrupt the balance of fat metabolism and lipolysis that can lead to abdominal fat deposition (Brown 2004). Researcher Richard Brown, MD, associate professor of clinical psychiatry at Columbia University College of Physicians and Surgeons and co-author of a comprehensive review of Rhodiola rosea and a book on the subject states “Many of our patients who take Rhodiola rosea for depression, anxiety or fatigue report a bonus benefit: as mood goes up, pounds go down.”
Rhodiola rosea extract was investigated for weight reduction and fat metabolism at Georgian State Hospital. Rhodiola rosea extract (300 mg) was administered three times daily before meals. Participants in control and placebo groups walked for 30 to 40 minutes after meals. Caloric intake and fast foods were restricted. Test subjects included 130 obese males and females aged 29 to 60 years old who were administered supplementation for a period of 90 days. The supplemented group lost an average 19 lbs. with 92% experiencing weight loss. The average body fat ratios decreased from 31% to 25%. The placebo group lost an average of 8 lbs. (Abidov 2003).
Rhodiola Rosea was examined for its effects as an appetite suppressant to curb binge eating. Investigators found that caloric deprivation followed by subsequent access to food prompted binge eating patterns in female rats. Rhodiola rosea supplementation promoted a significant reduction in binge eating and resulted in a decrease of stress-induced cortisol, the hormone associated with both elevated fat storage in the abdominal area and muscle loss when dieting (Cifani 2010).
A double blind, randomized placebo controlled study of 60 male and female volunteers, ages 20 to 55 was conducted to evaluate the efficacy of Rhodiola rosea root extract for its adaptogenic effects to treat individuals suffering from stress-related fatigue. One group of participants received a 576 mg extract/day), while the control group received a placebo. The 28 day study demonstrated that supplementation with R. rosea extract exerted a statistically significant anti-fatigue effect that increases mental performance, particularly concentration, and decreases cortisol response (Olsson 2009).
In a double bind, placebo controlled study Rhodiola rosea standardized to 3% rosarvins and 1% salidroside was shown to improve exercise performance and endurance in healthy young adults who consumed 200 mg of the extract one hour before exercise. Supplementation significantly increased their capacity for endurance exercise (De Bock 2004). Rhodiola appears to boost calorie-burning potential by at least 10%, and by as much as 70% during physical activity,” reports prominent physician and researcher Richard Brown, M.D.
Rhodiola rosea, has been reported to promote fatty acid utilization and to improve physical performance during strenuous exercise. A study was conducted to determine the effects of Rhodiola roseasupplementation in competitive athletes during endurance exercise. After receiving supplementation with Rhodiola rosea for 4 weeks, 14 trained male athletes underwent cardio-pulmonary exhaustion tests and blood sampling to compare biochemical parameters. Rhodiola rosea intake was shown to statistically reduce plasma free fatty acids levels, lactate levels and parameters of skeletal muscle damage after an exhaustive exercise session. Researchers contend this study confirms that Rhodiola rosea may increase adaptogenic ability to physical exercise while reducing fatty acid levels (Parisi 2010).
Rhodiola rosea (50 mg/kg) and Rhodiola crenulata (50 mg/kg) roots were investigated for their effect on the duration of exhaustive swimming and ATP energy content in mitochondria of skeletal muscles in rats. Supplementation with Rhodiola rosea extract significantly prolonged the duration of exhaustive swimming by 24% in comparison with control rats and R. crenulata supplemented rats.R. rosea extract was shown to activate the synthesis or re-synthesis of ATP in mitochondria and stimulate reparative energy processes after intense exercise to improve physical working capacity (Abidov 2003).
Rhodiola rosea has been used in the general population in Russia and elsewhere in the world for decades to alleviate everyday anxiety, depression, and insomnia. Based on this knowledge, investigators sought to evaluate whether Rhodiola rosea is effective in reducing symptoms of Generalized Anxiety Disorder (GAD). Participants experienced significant improvement in GAD symptoms following supplementation with R. rosea; results were similar to that found in clinical trials (Bystrisky 2007).
Richard P. Brown, MD, associate professor of clinical psychiatry at Columbia University College of Physicians and Surgeons, and a co-author of a comprehensive review of Rhodiola rosea and a book on the subject said, “two dose levels of Rhodiola rosea were found to significantly reduce symptoms of depression in patients with mild to moderate depression compared to placebo in this randomized clinical trial. In addition to mood elevation, evidence indicates that R. rosea has numerous other benefits, including enhancement of cognitive function, sexual function, and both mental and physical performance under stress. Additional studies are needed to explore and establish the potential applications of this herbal extract. In the meantime, phytomedicinal researchers and consumers can be encouraged by these findings.”
In a double-blind, 6-week, randomized, placebo-controlled study of Rhodiola rosea in patients diagnosed with depression, it was found that an extract of Rhodiola rosea roots and rhizomes demonstrated significant anti-depressive activity compared to the placebo group. Eighty-nine participants, aged 18 to 70, assessed with clinically significant depression were included in the study. One group received 340 mg daily; the second group received 680 mg daily, while the third group was given a placebo. At both dosages of Rhodiola rosea participants experienced statistically significant improvements in insomnia, emotional instability, and levels of somatization (the conversion of anxiety into physical symptoms) compared to insignificant changes in the placebo group. Researchers concluded that Rhodiola rosea demonstrates clear and significant anti-depressive activity in patients suffering from mild to moderate depression. They further noted that no adverse effects were noted in supplemented participants (Darbinyan 2007).
Rhodiola root extracts (100 mg/mL) were evaluated to test their inhibitory effects on monoamine oxidases (MAOs A and B) responsible for the breakdown of dopamine and serotonin. Water and methanol extracts of the supplement exhibited inhibitions of 92% and 84% on MAO A and 81% and 89% on MAO B, respectively. The most active compound, rosiridin promoted an inhibition over 80% on MAO B. The present investigation demonstrates that Rhodiola rosea roots have potent anti-depressant activity by inhibiting MAO A and may also find application in the control of senile dementia by their inhibition of MAO B (van Diermen 2009).
In a double-blind trial, 60 students were divided into experimental and control groups. The supplemental group received 100 mg of Rhodiola extract a day for 20 days and experienced significant improvements in physical work capacity, coordination, and general well-being with less mental fatigue and situational anxiety compared to the placebo group. The ability of these students to learn a language increased by 61% over the placebo group, while their relative fatigue levels decreased by 30%. Students receiving the supplement also scored higher on final exams (Spasov 2000).
“One of the great things about Rhodiola is that it is both calming and stimulating,” notes physician, researcher and author, Dr. Richard P. Brown. “Usually an herb or drug works only in one direction. Valium, for example, calms your brain but also makes it dull. Rhodiola, in contrast, calms the emotional system and yet is activating and energizing for the brain’s cognitive functions. To have these two benefits at the same time is quite unusual in nature. Rhodiola gets rid of the stress that often interferes with concentration and focus, but leaves your mind sharp and able to perform at its peak. Once people become aware of this herb, it will be very popular.”
Administration of Rhodiola rosea extract was studied for its effects on stress-induced cardiac damage. Rhodiola rosea was found to prevent stress-induced cardiac damage and determined to prevent stress-induced catecholamine release in the myocardium while lowering adrenal catecholamines (Maslova 1994).
VITAMINS AND MINERALS
A randomized, double-blind, placebo-controlled trial was conducted to evaluate the efficacy of a vitamin B complex nutritional supplement for improving depressive and anxiety symptoms according to the Beck Depression and Anxiety Inventories in 60 adults diagnosed with depressive disorders. Participants were assessed at baseline and at 30 and 60 days. Results of supplementation indicated significant and more continuous improvements in depressive and anxiety symptoms compared to placebo (Lewis 2013).
In a first time randomized, double-blind study investigators examined the efficacy of 3-months administration of two forms of high dose vitamin B complex on mood and psychological strain associated with chronic work stress. Sixty participants completed a trial in which personality, work demands, mood, anxiety, and strain were assessed. Results of the study indicated that the vitamin B complex supplemented groups reported significantly lower personal strain and a reduction in confusion and depressed mood after 12 weeks. The results of the study were consistent with a prior study that indicated decreased workplace stress after 90 days of supplementation with a B multivitamin. These findings may have important personal health, organizational and societal outcomes given the rising costs of healthcare and incidence of workplace stress (Stough 2011).
It is hypothesized that certain demographic groups may be at risk for inadequate micronutrient uptake leading to tiredness, fatigue and low energy levels. A number of vitamins and minerals participate in the metabolism of carbohydrates, proteins, and lipids to provide cellular energy in the form of adenosine triphosphate (ATP). Inadequate intake of vitamins and minerals can lead to diminished energy production and affect both general and exercise performance. Micronutrient supplementation can positively influence outcomes associated with inadequate intake or deficiency (Huskisson, 2007).
Free radicals adversely alter lipids, proteins, and DNA which are the cause many human diseases. Antioxidants have the capacity to cope with these oxidative stresses. Oxidative stress is believed to occur in atherosclerosis, inflammatory disease, some cancers, and the aging process. Oxidative stress is thought to significantly contribute to “all inflammatory diseases (arthritis, vasculitis, glomerulonephritis, lupus erythematous, adult respiratory diseases syndrome), ischemic diseases (heart diseases, stroke, intestinal ischema), hemochromatosis, acquired immunodeficiency syndrome, emphysema, organ transplantation, gastric ulcers, hypertension and preeclampsia, neurological disorder (Alzheimer’s disease, Parkinson’s disease, muscular dystrophy), alcoholism, smoking-related diseases, and many others”. Antioxidants known as vitamins A, C, and E have revolutionized research efforts and gained significance as important antioxidants in the physiology of living organisms. Antioxidants are able to prevent free radical induced tissue damage in several ways that include preventing the formation of free radicals or scavenging them or by enhancing their decomposition (Lobo 2010).
The US population is deficient in several vitamins and minerals and does not meet the estimated average requirement (EAR) for the following: vitamin E (93%), magnesium (56%), vitamin A (44%), vitamin C (31%), vitamin B6 (14%), and zinc (12%) according to the National Health and Nutrition Examination Survey (NHANES) (Moshfegh 2005). According to the Institute of Medicine, EAR data is used to establish the recommended dietary allowance (RDA) for individuals in conjunction with other data (Institute of Medicine). Vitamin D deficiency poses a significant issue in the US and across the globe. It’s estimated that 1 billion people in the world do not have adequate vitamin D intake (Holick 2007).
A meta-analysis of studies was conducted to determine the relative risks (95% confidence intervals) for correlation between magnesium intake and incidence of type 2 diabetes involving more than 250,000 participants and more than 10,000 studies. All studies examined found an inverse relationship between magnesium intake and risk of type 2 diabetes when both dietary and supplemented magnesium were evaluated with the exception of one study. These findings suggest that increasing dietary or supplemented magnesium may reduce the risk of type 2 diabetes (Wolk 2010).
The Atherosclerosis Risk in Communities Study evaluated risk factors and serum magnesium (Mg) levels in over 14,000 participants 45 to 64-years old. Follow up continued for a period of 12 years. 264 cases of sudden coronary death (SCD) were observed. Proportional hazards regression was used to assess the correlation of serum Mg with risk of SCD. Those participants in the highest quartile of serum Mg were found to be at significantly lower risk (almost 40%) of SCD. This correlation persisted when adjusted for potential contributing variables. Researchers concluded that Mg supplementation should be considered for those individuals at high risk for SCD (Peacock 2010).
Magnesium is critical to the metabolism of carbohydrates and fats for energy production that relies upon numerous magnesium-dependent chemical reactions. Magnesium is an essential component in the adenosine triphosphate (ATP) synthesis in mitochondria, often referred to as the powerhouse of the cell. ATP is responsible for energy production for most metabolic processes. As such, it exists primarily as a complex with magnesium or MgATP (Rude 2006).
Researchers from the Center for Learning and Memory, School of Medicine at the University of Texas in Austin found that elevated brain levels of magnesium can assist with altering debilitating memories resulting from stressful experiences by helping to create new response patterns not influenced by fear or anxiety. Researchers gave supplemental magnesium to test subjects and found that elevated magnesium in the brain induced the production of brain-derived neurotrophic factor (BDNF), a compound used by the brain to rejuvenate cellular function. Scientists concluded that increased magnesium levels led to increased synaptic plasticity that allowed the learned fear response to become altered. Researchers concluded that the ability to alter the effects of intense fear and anxiety may improve quality of life, healthy cognition, and memory development (Nashat 2011; Barbagallo 2011; Byron 2010).
Multiple controlled, human trials have supported the link between magnesium deficiency and anxiety. In a thirty day randomized, double-blind study, 80 participants were given magnesium supplementation in combination with a multivitamin, zinc and calcium. Magnesium dramatically decreased symptoms of stress and anxiety compared to a placebo (Carroll 2000). Magnesium and vitamin B6 supplementation effectively reduced premenstrual related anxiety in 44 female volunteers in a randomized, double-blind crossover study (De Souza2000). In a randomized, controlled placebo based study in which 264 patients were provided dietary magnesium supplements, participants demonstrated clinical improvement in Generalized Anxiety Disorder (Hanus 2004).
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