Nutraceuticals For Treating Adrenocortical Dysfunction


Phosphatidylserine is an endogenous phospholipid found in high levels in the brain and is important in neuron function. Soy lecithin phosphatidylserine has been shown to have adap-togenic properties and modulates the HPA axis. Studies show that in the presence of a

Table 1-2. Nutraceuticals for Treating Adrenocortical Dysfunction


Mechanism of Action

Vitamin C

Pantothenic acid Vitamin B complex Phosphatidylserine


Zinc a-lipoic acid

Adrenal glandular support

1,QQQmg, 3 times per day

5QQ mg, 2 times per day

5Q-1QQ mg, per day

5QQmg, 2 times per day, 15 minutes prior to eating

15Q mg, 3 times per day

15 mg, 2 times per day, with food

150 mg, 3 times per day

4QQ-5QQ mg, per day or as directed by manufacturer

Acts as a reducing agent for the mixed function oxidase used in the synthesis of steroid hormones3 Increases corticosteroid production and normalizes response to ACTHb Helps to transfer methyl groups and regenerate methionine Orally, prescribed PS product has decreased plasma cortisol and ACTH levels in healthy research subjectsc A cofactor for most ATP-dependent reactions and activation of intracellular secondary messenger cAMP Zinc deficiency increases membrane susceptibility to oxygen free-radical damage

Cofactor for the citric-acid cycle; potent antioxidant; partially restores the hydrocortisone suppression of T-helper cell activityd Unknown; further research is needed aKodama M, Inoue F, Kodama T. Intraperitoneal administration of ascorbic acid delays the turnover of labeled cortisol in plasma of ODA rat, but not Wistar rat: Evidence in support of the cardinal role of vitamin C in the progression of glucocorticoid synthesis. In Vivo 1996;10:97-110

bPietrzik K, Ginta E. Response of hepatitis drug-metabolizing enzymes to immobilization stress in rats of various ages. Acta Physiol Hungarica 1993;81:29-35.

cMonteleone P, Maj M, Beinert L, et al. Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men. Eur J Clin Pharmacol 1992;41:385-388. dOhmori H, Yamauchi T, Yamamoto I. Augmentation of the antibody response by lipoic acid in mice. Jpn J Pharmacol 1986;42:275-280.

ACTH, adrenocoricotropic hormone; ATP, adenosine triphosphate; cAMP, cyclic adensosine monophosphate; PS, phosphatidylserine.

psychological stressor, phosphatidylserine supplementation blunts serum cortisol, ACTH, and salivary cortisol levels.107 Additionally, research has shown that phosphatidylserine supplementation in individuals with above-average neuroticism scores reported better moods and feeling less stressed.108 Results also indicate that phosphatidylserine improves cognitive function on tasks such as learning and memory skills in elderly individuals.109 In addition, studies demonstrate improvement in depression, cognition, and behavior in elderly individuals with phosphatidylserine.110

L-Tyrosine and L-Phenylalanine

Tyrosine is a nonessential amino acid synthesized from phenylalanine. It is the precursor used for the synthesis of thyroxine, catecholamines, norepinephrine, epinephrine, and dopamine. Studies have associated stress-induced impairment of performance with depletion of brain stores of norepinephrine. Tyrosine supplementation has been shown to improve stress-associated declines in both neural norepinephrine levels and performance.111 Also, individuals given tyrosine supplementation performed better on a memory and a tracking task under psychosocial and physical stress. In addition, the supplementation of tyrosine decreased systolic blood pressure in these individuals.112

Ascorbic Acid

Ascorbic acid, or vitamin C, is a water-soluble vitamin important for numerous physiological functions. In addition to antioxidant and immune-stimulating activity, it is also involved with tyrosine, tryptophan, norepinephrine, dopamine, thyroxine, and carnitine metabolism. A study was performed to evaluate the effect of ascorbic acid supplementation with psychological stress. The group given the ascorbic acid showed less increase in blood pressure, decreased subjective stress response, and a faster cortisol recovery.113 In one study, ascorbic acid supplementation was given to individuals undergoing prolonged exercise. Cortisol was significantly reduced immediately post-exercise, as well as epinephrine, interleukin-10, and interleukin-1 receptor antagonist.114 Evidence also shows that animals deficient in ascorbic acid have significantly higher serum and saliva cortisol levels.115

B Vitamins

B vitamins, such as pyridoxine, pantothenic acid, thiamine, and cobalamin, have been shown to improve aspects of the stress response and stress-related disease. Pyridoxine, or vitamin B6, is required for amino acid, carbohydrate, and lipid metabolism. Pyridoxine has been shown by numerous studies to modulate the stress response. Animal studies indicate that pyridoxine deficiency causes hypertension and increased sympathetic stimulation and decreased serotonin, gamma-aminobutyric acid (GABA) and pyridoxal phosphate. Pyridoxine supplementation in these animals reversed these finding demonstrating normal GABA, serotonin, epinephrine and norepinephrine levels.116 Vitamin B6 is associated with increased risk of cardiovascular disease. Low levels of pyridoxal 5°-phosphate, the active form of vitamin B6, is associated with elevation in the inflammatory marker CRP independent of homocysteine levels.117 Low levels of vitamin B6, B12, and folate are associated with increased homocysteine and risk for coronary heart disease.118 Thiamine, or vitamin B1, has also shown anti-stress activity in animals by protecting cardiac tissue from stress-induced ischemia.119 Deficiency of thiamine is also associated with memory and learning deficits.120

Omega-3 Fatty Acids

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are omega-3 fatty acids found in high concentration in fish, such as salmon, cod, mackerel, trout, sardines, and herring. Research has shown that supplementation with omega-3 fatty acids blunt the stress response elicited by mental stress. In fact, epinephrine, cortisol, plasma nonesterified fatty acids, and energy expenditure were all significantly decreased with dietary fish oil supplementation.121 Fish oil also has anti-inflammatory activity by inhibiting the pro-inflammatory cytokines in-terleukin-1 alpha and TNF-alpha as well as decrease COX-2 expression.122 Studies also show that omega-3 deficiency adversely affects learning and cognitive behavior.123 Evidence suggests that fish oil is beneficial for prevention of cardiovascular disease, type 2 diabetes, metabolic syndrome, hyperlipidemia, and depression.124

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