Phytosterols include hundreds of plant-derived sterol compounds (including sterols and sterolins) that bear structural similarity to the cholesterol made in our bodies, but none of the artery-clogging effects. The most prevalent phytosterols in the diet are beta-sitosterol (BS), campesterol, and stigmasterol. Plant oils contain the highest concentration of phytosterols, so nuts and seeds have fairly high levels, and all fruits and vegetables generally contain some. Perhaps the best way to obtain phytosterols is to eat a diet rich in fruits, vegetables, nuts, and seeds—which obviously would bring numerous other benefits as well.
Phytosterols appear to help modulate immune function, inflammation, and pain levels through their effects on controlling the production of inflammatory cytokines. This modulation of cytokine production and activity may also help to control allergies and reduce prostate enlargement. In athletes competing in marathons and other stressful endurance events, phytosterols are known to reduce cortisol levels, maintain DHEA levels, and prevent the typical suppression of immune-system function seen after such events. From test-tube and animal studies, it appears that phytosterols such as beta-sitosterol can influence the structure and function of cell membranes in both healthy and cancerous tissue. This effect is known to alter cellular signaling pathways that regulate tumor growth and apoptosis (cell death); it provides a possible explanation for the stimulation of immune function observed following beta-sitosterol supplementation.
In several animal studies examining the effect of beta-sitosterol consumption on experimentally induced breast cancer, the animals fed phytosterols (including beta-sitosterol) showed a dramatic (30–80 percent) reduction in tumor size and a 10–30 percent lower incidence of metastases to the lymph nodes and lungs compared to a control group. From these animal studies, there is strong preliminary evidence that dietary phytosterols do indeed retard the growth and spread of breast cancer cells.
In terms of general immune function, beta-sitosterol has been shown in humans to normalize the function of T-helper lymphocytes and natural killer cells following stressful events, such as marathon running, that normally suppress immune-system function. In addition to alleviating much of the postexercise immune suppression that occurs following endurance competitions, beta-sitosterol has also been shown to normalize the ratio of catabolic stress hormones (i.e., those that break down tissue, such as cortisol) to anabolic (rebuilding) hormones such as DHEA.
In one small study, seventeen endurance runners completed a sixty-eight-kilometer run (about forty miles) and afterward received either 60 mg of beta-sitosterol (nine runners) or a placebo (eight runners) for four weeks. Those runners receiving the beta-sitosterol supplements showed a significant drop in their cortisol-to-DHEA ratio (indicating less stress) as well as reduced inflammation and a markedly lower immunosuppression. Using the ultramarathon as a model for overall stress, researchers concluded that beta-sitosterol is effective in modulating the stress response by managing cortisol levels within a more normal range.
Phytosterols are generally regarded as quite safe because of their widespread distribution in fruits and vegetables. No significant side effects or drug interactions have been reported in any of the studies investigating beta-sitosterol. The typical dosage recommended to achieve the best cortisol-control and immune-function benefits is 100–300 mg per day of a mixed phytosterol blend, including 60–120 mg per day of beta-sitosterol. A handful of roasted peanuts or a couple of tablespoons of peanut butter contain about 10–30 mg of beta-sitosterol, so a few handfuls of Planter's nuts or a scoop of Skippy will supply an effective dose of immune enhancement following exercise (but also a whopping dose of calories).
Because phytosterols afford other health benefits in addition to their role in cortisol control, they are often found in commercial supplements designed for lowering cholesterol, boosting immune function, and maintaining prostate health. Almost always, the phytosterols will be combined with additional ingredients to enhance the primary effect (for example, they might be blended with echinacea in immune-boosting products).
Phosphatidylserine (PS) is a phospholipid—meaning that it is composed of fatty acids (lipids) and phosphate. PS is concentrated in the brain cells, where it is thought to be related to brain-cell function, but it is also found in all cell membranes, where it is thought to play key roles in muscle metabolism and immune-system function. PS has also been shown to modulate many aspects of cortisol overproduction, especially following intense exercise.
There is ample scientific evidence that PS supplementation, in a dose of 100–300 mg per day, can help improve mental function and decrease feelings of depression, even in cases as severe as Alzheimer's disease and other forms of age-related mental decline. More recent studies from Italy have shown much larger doses of PS (400–800 mg per day) to reduce cortisol levels by 15–30 percent following heavy exercise. Because cortisol is catabolic toward muscle tissue (that is, it leads to protein breakdown and muscle loss), athletes frequently use PS supplements to help promote recovery from exercise and decrease slow muscle loss. And because of its benefits in improving cognitive function, PS could also be considered a general antistress nutrient, providing benefits not only for athletes subjected to the physical stress of exercise, but also for individuals who are under chronic emotional stress from hectic lifestyles, job deadlines, and many of the other stresses of a modern, Type C lifestyle.
There do not appear to be any significant side effects associated with dietary supplements containing phosphatidylserine, but due to concerns about mad-cow disease, it is generally recommended to select PS supplements derived from soybeans versus those extracted from cows' brains.
Concentrated PS supplements are available in doses of 50–100 mg per day, and they are quite expensive. For brain and mental support, 100–500 mg per day of PS is recommended for a month or so, followed by a lower maintenance dose of approximately 50–100 mg per day. Athletes may need as much as 800 mg per day immediately before or after intense training to help suppress cortisol secretion and promote muscle recovery. This amount of PS would cost several hundred dollars per month, making these levels less than viable for the average consumer.
Ken was an avid runner, regularly competing in 10K races and occasional marathons. Frustrated with his apparent inability to fully recover between strenuous workouts and intense competitions, despite a regimen of active rest and balanced nutrition, Ken turned to a combination of supplements that included phosphatidylserine (PS) and beta-sitosterol (BS). Both PS and BS have been shown to help athletes reduce the rise in cortisol that is seen during intense exercise. Because elevated cortisol levels are catabolic toward connective tissues such as muscle, tendons, and ligaments—that is, they accelerate the breakdown of these tissues—keeping cortisol levels from rising too high during exercise can be an effective strategy for reducing tissue breakdown and enhancing the repair process.
The combination of PS (50 mg per day) with BS (200 mg per day), taken immediately following each workout, helped Ken's body to control cortisol levels and accelerate his postexercise recovery. The primary end benefit for Ken was a heightened ability to train intensely without getting injured and, thus, to improve his overall performance in his races.
Tyrosine is an amino acid that has been studied by the U.S. military as a potential antistress nutrient to help soldiers cope with the stress of battle. Findings from several studies suggest that dietary tyrosine supplements can help to reduce the acute effects of stress and fatigue on physical and mental performance. Chronic stress can reduce brain levels of neurotransmitters such as epinephrine, norepinephrine, and dopamine, a phenomenon thought to be related to some of the decline in mental and physical performance during stressful events. Because the brain uses tyrosine to synthesize these neurotransmitters, dietary tyrosine supplements can help slow their depletion and reduce the declines in performance that are often noted during stressful events. And because neurotransmitters play a role in overall brain function, including depression and other mood disorders, tyrosine supplementation has been studied for its effects on stress, mental function, and Alzheimer's disease.
In soldiers, this theory has been proven under conditions of combat training, sleep deprivation, cold exposure, and extremes of physical exercise. Studies of military cadets undergoing combat training showed that 2,000 mg of tyrosine aided memory and cognitive ability during stress. In other (nonsoldier) studies, tyrosine supplements (100–200 mg per day) were able to offset declines in performance and ability to concentrate in volunteers exposed to stressful situations such as shift work, sleep deprivation, and fatigue.
In animals, dietary tyrosine supplementation has been shown to improve learning ability and memory (ability to navigate a maze), while tyrosine depletion has led to decreased performance, probably via suppressed norepinephrine levels. Tyrosine and norepinephrine levels are often reduced in people with depression or under conditions of stress, and in some forms of obesity. In animal experiments, tyrosine supplementation leads to a slight elevation in oxygen consumption, suggesting an effect on increasing metabolic rate.
In one human study, 6–8 grams of tyrosine or a placebo was given to volunteers subjected to a cardiovascular stress test. Those receiving the tyrosine supplements showed improvements in attention and cognitive function compared to the placebo group. In another study, subjects were given either a placebo or 6–7 grams of tyrosine, in random order on two consecutive days. One hour later, subjects were asked to perform a number of stress-sensitive tasks while simultaneously being exposed to a stressor (loud noise). During the tyrosine supplementation, subjects showed improved performance and decreased blood pressure throughout the study period. In an additional double-blind, placebo-controlled crossover study, subjects receiving 6–7 grams of tyrosine showed a significant improvement in stress symptoms, mood disturbances, and performance impairments during exposure to extreme stress (four and a half hours of cold and low oxygen). Overall, these studies suggest that tyrosine is effective in modulating the stress response in a variety of stressful conditions.
Since tyrosine is relatively abundant in protein-containing foods, it is unlikely that tyrosine supplementation at the levels commonly available would cause significant side effects. Human studies have been conducted with 6–8 grams of tyrosine per day, with no adverse effects noted. (Because of the high cost of tyrosine supplements, commercially available products tend to provide no more than a few hundred milligrams—that is, less than 10 percent of the levels shown to be effective against stress in clinical studies.) Extremely high doses of any isolated amino acid are not recommended, however, as they may cause unpleasant gastrointestinal side effects such as diarrhea, nausea, and vomiting, as well as headaches and nervousness.
Branched-Chain Amino Acids
The group of amino acids referred to as the branched-chain amino acids (BCAAs) is comprised of three essential amino acids: valine, leucine, and isoleucine. The recommended intake for the BCAAs is about 3 grams per day, an amount that should be easily obtained from protein foods. Supplemental levels have been used at doses from 3 grams to more than 20 grams per day to increase endurance, reduce fatigue, improve mental performance, increase energy levels, prevent immune-system suppression, and counteract muscle catabolism following intense exercise.
In numerous studies of athletes, BCAAs have been shown to maintain blood levels of glutamine, an amino acid used as fuel by immune-system cells. During intense exercise, glutamine levels typically fall dramatically, removing the primary fuel source for immune cells and leading to a general suppression of immune-system activity (and an increased risk of infections) following the exercise. By supplementing with either glutamine or BCAAs, a person can maintain blood levels of glutamine and thereby avoid suppression of immune-cell activity due to a lack of fuel.
In related studies, BCAA supplements have been shown to bear a beneficial effect on counteracting the rise in cortisol and the drop in testosterone that is often seen in endurance athletes undergoing stressful training. In these studies, intense exercise is used as a model for high stress, so the increased cortisol levels and the reduced testosterone levels are exactly what happen in the rest of us when we experience a stressful situation at work, at home, or while standing in line at the grocery store.
Supplemental intakes of the BCAAs (3–20 grams per day) have been studied in tablet and liquid form with no reported adverse side effects, aside from minor gastrointestinal complaints. Higher intakes should be avoided due to the possibility of blocking the absorption of other amino acids from the diet and the risk of more severe gastrointestinal distress. Unfortunately, because purified sources of the BCAAs are so expensive, commercial products typically provide only a small fraction of the multigram doses that have been studied for performance and recovery.
Summary: Cortisol Controllers
The seven supplements discussed in this section—magnolia bark, theanine, epimedium, phytosterols, phosphatidylserine, tyrosine, and BCAAs—represent the most promising natural compounds for directly controlling stress and modulating cortisol levels. But which of them should you choose? One? Three? All seven?
As discussed in Chapter 4, HSD (11-beta-hydroxysteroid-dehydrogenase-1) is an enzyme within fat cells that is responsible for converting inactive cortisol into active cortisol, which can then serve as a potent fat-storage signal. As such, you do not want to have an overactive HSD enzyme sabotaging your weight-loss efforts. Remember, too much HSD means too much cortisol inside your fat cells and too much fat stored in your belly region.
Every major pharmaceutical company in the world is aggressively developing (and patenting) synthetic molecules to inhibit the activity of HSD and treat obesity and diabetes—but those drugs are still five to ten years away from reaching the market. Luckily, a number of natural flavonoids are known to inhibit HSD, including those from grapefruit juice (naringenin), licorice (glycyrrhizin), soybeans (daidzein and genistein), apples (quercetin), and Chinese medicinal herbs (magnolia/magnolol, Perillae frutescens, Zizyphus vulgaris, and Scutellaria baicalensis).
A very unique class of flavonoids, known as polymethoxylated flavones (PMFs), particularly tangeritin, sinensetin, and nobilitin, represent a class of "super flavonoids," extracted from citrus peels, that exhibit approximately threefold potency compared to other flavonoids. Polymethoxylated flavones are just what they sound like—flavonoid compounds with extra methoxy groups compared to "regular" flavones. Like all flavonoids, the PMFs deliver potent antioxidant and anti-inflammatory activity, but the PMF version is about three times more potent in its ability to reduce both HSD activity and cholesterol levels (clinical studies show a 20–30 percent reduction).
PMFs are wonderfully safe—and at the effective dose of 300 mg daily (see below), users will benefit from the antioxidant and anti-inflammatory effects in addition to the HSD- and cholesterol-reducing effects. Unlike some flavonoids, such as naringin from grapefruit, there are no known risks of drug interactions with citrus-derived PMFs. (Certain grapefruit flavonoids can interfere with the liver enzymes needed to metabolize many prescription drugs.)
Our lab was the first in the world to use PMFs for inhibiting the activity of HSD, and thus also reducing systemic and local cortisol concentrations (in the liver and adipose tissue), while also promoting blood-sugar control and weight loss. As part of the SENSE Lifestyle Program, we provided supplements of PMFs (with Eurycoma root extract—see below in the section on testosterone) to a group of moderately overweight subjects. The PMFs (300 mg of citrus peel extract/day) reduced cortisol levels by 20 percent, body weight by 5 percent, body fat by 6 percent, and waist circumference by 8 percent over a period of six weeks. A longer twelve-week study showed even better results, with additional beneficial effects on reducing cholesterol (–20 percent), boosting mood (+25 percent), reducing fatigue (–48 percent), and maintaining normal testosterone levels and resting metabolic rate.