1. Lose Weight
2. Get a Better Education
3. Get Fit
4. Eat Healthy Food
5. Manage Stress

Coming in to 2023, according to Statisa.com, America’s top New Year’s resolutions were¹:

What are your up coming New Year’s Resolutions going to be?

Lose Weight

Of course it’s easy to make resolutions, but hard to keep them. So what can you do to make it easier? While there is no substitute for willpower and commitment, this article will review some nutraceuticals which may actually help you be more effective at adhering to resolutions.

We all know that diet and exercise are necessary components for a successful weight loss program. In addition there are nutraceuticals which can also help. Two of these are L-carnitine and Garcinia cambogia.

L-carnitine
The amino acid L-carnitine plays an important role in energy production by chaperoning activated fatty acids into the mitochondrial matrix to be metabolized.² Unfortunately, research suggests that being overweight is associated with carnitine insufficiency, Studies have also shown that supplementation with L-carnitine is capable of promoting greater weight loss than with diet and exercise alone (500 mg-3 g/day),^4,5,6 and improving various measures of exercise performance and recovery (2 g/day).^{7,8,9,10,11,12,13,14}

Garcina cambogia
Garcina cambogia is a tropical plant that contains a compound known as (-)-hydroxycitric acid (HCA)—which has some interesting biological properties.¹⁵ Specifically, research indicates that HCA may help reduce the conversion of carbohydrates into fatty acids,^17,18 which could mean less fat stored in your fat cells. Also, research^{19,20,21,22,23,24} suggests that HCA may help reduce appetite and food intake. In one study with overweight men and women,²⁵ 300 mg HCA (as G. cambogia extract standardized for HCA), three times daily, 60 minutes before lunch and dinner, and 2 hours after dinner (to prevent snacking in the evening) resulted in 15–30 percent reduced calorie intake. Furthermore, human clinical research26 demonstrated that 440 mg HCA three times daily, 30 minutes prior to breakfast, lunch and dinner (as G. cambogia extract standardized for HCA) resulted in 14 lbs weight loss, compared to 8 lbs weight loss with diet and exercise alone (1200 calories/ day low fat diet, exercise 3 times/week). Other research has shown similar results.^27,28,29

GET A BETTER EDUCATION

Arguably, getting a better education will take more of a time commitment than any other resolution discussed in this article. Of course it’s also the resolution that is most likely to get you a better job and outlook for the future. Nevertheless, it will involve a great deal of reading and studying, which means that you need to have a good memory and good cognitive function. Phosphatidylserine (PS) may be able to help. PS is an integral component in the structure of the brain and spinal cord, and a significant amount of published clinical research has demonstrated that PS supplementation supports various cognitive parameters in adults and in children.³⁰ This is an important consideration if you’re a middle-aged adult going back to school, because that’s the time that age-related memory impairment can start to rear its ugly head. Luckily, research^31,32,33,34 has shown that 100–300 mg of PS daily has helped reduce memory complaints and improve memory difficulties (including learning and remembering written information) in age-related memory impairment. PS can also help young adult students. This was shown in a study³⁵ on 17–18 year old students who received 100 mg of PS daily. Supplementation with PS resulted in significant improvement in memory and improved cognitive performance in students.

GET FIT

Getting fit is primarily a function of a regular exercise program, as well as good nutrition. Naturally, anything that can help you achieve results more quickly or effectively is desirable— assuming that we’re talking about something healthy and legal. In this case, L-arginine, beta-alanine and branched-chain amino acids fit the bill exactly.

L-arginine
The amino acid L-arginine is a precursor to nitric oxide, a vasodilator produced by the body to facilitate circulation.³⁶ Consequently, supplementation with L-arginine has been shown to increase oxygen transport during exercise and improve aerobic exercise (6 g/day)^37,38 and increase circulating growth hormone levels in response to exercise (5–9 g/day, 30 minutes before exercise);³⁹ and growth hormone can help support the development of new muscle.

Beta-alanine
Research suggests that during high-intensity exercise and strength training, 2.4 grams to 6.4 grams daily of the amino acid beta-alanine improves some measures of physical performance (e.g. increases ventilatory threshold, time to onset of muscle fatigue, time to exhaustion, and total work). A meta-analysis of 15 studies demonstrated that beta-alanine significantly improved exercise measures compared to placebo.⁴⁰

Branched-chain amino acids
Leucine, isoleucine and valine are collectively referred to as the branched-chain amino acids (BCAAs). BCAAs have also been shown to significantly reduce the breakdown of skeletal muscle in normal and exercising Volunteers,^{41,42,43,45,46} decrease muscle soreness and muscle fatigue occurring for a few days after exercise,^47,48 and decrease lactic acid levels during exercise.^49,50,51,52 Doses of 1.3–5.7 g/day have been used.

EAT HEALTHY FOOD

If you think you need to eat a healthier diet, you’re in good company. According the USDA, only 10 percent of the American population eats a good diet.⁵³ So by all means, take every measure possible to eat healthier food. At the same time it’s important to realize that even when your diet improves, that doesn’t necessarily mean that you’ll be getting all of the vitamins and minerals you need. In fact, according to the goals of nutrient intake established by the USDA,⁵⁴ comparing the nutritional goals for Americans to the nutrient content of foods consumed in a 2000 calorie per day diet, there will be insufficient amounts of vitamin D, vitamin E, choline, magnesium (for men only) and potassium. So even if you follow dietary guidelines there is a good chance that you still won’t be reaching 100 percent of your nutrient intake goals.

This doesn’t mean that you shouldn’t bother eating a healthy diet; it just means that you need a nutrition insurance policy in the form of a good daily multivitamin. Not only will this help assure that you fill in the missing nutrient gaps,⁵⁵ but research suggests that a good daily multivitamin may offer other benefits as well, which include supporting better cardiovascular health,^{56,57,58,59,60,61} reducing the risk of certain types of cancer,⁶² improving stress and energy,^63,64,65 and maybe even help you live longer.⁶⁶

MANAGE STRESS

Given the many adverse effects that stress can have on our lives, it makes very good sense to try and manage it better. While this can and should include attempts to decrease external stressors, it can also include techniques like biofeedback to help you remain calmer in the face of stress. Another complementary approach is the use of L-theanine and lemon balm.
L-theanine
Asian cultures have often used teas for relaxation effects. The relaxing effect is, at least in part, caused by the presence of a neurologically active amino acid, L-theanine. In research, L-theanine was shown to significantly increase brain activity in the alpha frequency band (calming brain waves), and improve mental alertness while promoting relaxation,^67,68 L-theanine has also been shown to induce feelings of tranquility in subjects⁶⁹ and have a direct anti-stress effect via the inhibition of cortical neuron excitation (50–200 mg).⁷⁰

Lemon balm
The herb lemon balm is often used as a mild mood elevator and calming herb in people with anxiety. It has been shown to improve attention and calmness in healthy volunteers.⁷¹ In human clinical research,⁷² 600 mg lemon balm extract improved the negative mood effects of stress, with significantly increased self-ratings of calmness. Also, the European Scientific Cooperative on Phytotherapy (an umbrella organization representing national herbal medicine or phytotherapy [aka, herbal medicine] associations across Europe), lists tenseness, restlessness and irritability among the uses for lemon balm.⁷³ The use of lemon balm as a brewed herb offers the additional benefit of delivering the herb as a warm beverage, adding to its soothing qualities.

Conclusion
The use of the nutraceuticals discussed in this article won’t guarantee that you will stick to your New Year’s resolution. You still need willpower and commitment. That being said, these nutraceuticals will provide you with extra support, and they may help you be more effective at adhering to your resolutions.

References
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7-keto DHEA is a metabolite of DHEA and may prove to be a safer alternative. Unlike DHEA, 7-keto-DHEA is not converted to androgens and estrogens.^9,10,11 Oral or topical administration of 7-keto-DHEA does not affect plasma levels of steroid hormones.^12,13 Similarly to DHEA, 7-keto-DHEA is rapidly converted to the sulfated form, known as 7-keto-DHEAS¹⁴.

Areas Of Benefit
Clinical studies have been conducted on supplementation with both DHEA and 7-keto-DHEA. Based upon that research, DHEA offers potential benefits for adrenal support, youthful skin, sexual support, bone mineral density, mood support/ mental function, healthy inflammatory response in body tissues, fatigue reduction, menopause, weight loss, and insulin sensitivity. Clinical studies on 7-keto DHEA have identified three major areas of potential benefit, including weight loss, cognitive function, and immune function. Following is an overview of the research on each of these dietary supplement ingredients.

DHEA: Adrenal Support
In individuals with suboptimal adrenal function, daily supplementation with 20–50 mg DHEA seems to improve feelings of well-being, skin and hair, and sexuality responsiveness.^15,16 DHEA also helps support healthy maturation of the adrenal glands in children with sub-optimal adrenal function.¹⁷

DHEA: Youthful Skin
As previously discussed. DHEA levels decline with age. In research with individuals 60–79 years old, taking 50 mg DHEA daily helped reverse certain parameters of aging skin. Subjects experienced an increase in epidermal thickness, sebum production, skin hydration, and decrease facial skin pigmentation.¹⁸

DHEA: Sexual Support
Aging males supplemented with 50 mg DHEA daily for six months experienced improvements in parameters of male performance, including erection, orgasmic function, sexual desire, and overall sexual satisfaction. DHEA helped improve male performance in men with sub-optimal blood pressure balance or whose performance was sub-optimal for unknown reasons, but did not improve performance in individuals with diabetes or neurological disorders.^19,20

In postmenopausal women, clinical evidence has demonstrated that a single 300 mg dose of DHEA improved sexual response, including significantly greater mental and physical sexual arousal.²¹ Furthermore, vaginal application of DHEA was found to be effective in reducing vaginal atrophy in elderly postmenopausal women.₂₂

DHEA: Bone Mineral Density
Loss of bone mineral density (BMD) is common with aging. Daily supplementation with 50–100 mg DHEA has been shown to improve BMD in older women and men with sub-optimal BMD._23,24 It also helps improve BMD in younger women with eating disorders.²⁵

DHEA: Mood Support / Mental Function
Experiencing moodiness or “the blues” is common during the lifecycle but can increase with age.²⁶ Some clinical research suggests that taking DHEA orally might improve symptoms of moodiness in elderly subjects.^27,28,29 Taking DHEA orally seems to improve healthy mental function in individuals with sub-optimal perception or expression of reality.³⁰

DHEA: Healthy Inflammatory Response In Body Tissues
Some individuals experience acute and chronic inflammation of various tissues of the body resulting from an attack by their body’s own immune system. Taking DHEA orally in conjunction with conventional treatment may help support a healthy inflammatory response in various tissues.^{31,32,33,34,35,36,37} It may also help promote the normalization of symptoms such as muscle ache.38 In addition, DHEA also seems to improve bone mineral density in such individuals whose conventional medications adversely affect bone mineral density.^39,40,41

DHEA: Fatigue Reduction
Some individuals, who experience a period of high physical and/or emotional stress, also experience the onset of fatigue of a chronic nature. DHEA may be able to help. In a clinical study, supplementation with DHEA led to a significant reduction in associated pain, fatigue, limitations in activities of daily living, helplessness, anxiety, difficulty thinking, poor memory, and sexual problems over the period of the study.⁴²

DHEA: Menopause
In a clinical study, 25 mg of DHEA daily increased the levels of all the hormones that derive from DHEA metabolism. It also increased neurosteroids and endorphin levels. The results were an improvement of vasomotor symptoms such as hot flashes, as well as psychological symptoms throughout 12 months of therapy.⁴³

DHEA: Weight Loss & Insulin Sensitivity
In a randomized, double-blind, placebo-controlled study, 56 elderly subjects took 50 mg DHEA daily for six months. Subjects taking the DHEA experienced a significant decrease in abdominal fat, and improvements in insulin sensitivity compared to those using the placebo.⁴⁴

7-keto: Weight Loss
7-keto-DHEA is thought to be beneficial in weight loss by increasing metabolism and thermogenesis. Early evidence in animals suggests 7-keto-DHEA can increase thermogenesis, possibly by stimulation of thermogenic enzymes in the liver⁴⁵ ; however this effect has not yet been reported in humans. Clinical evidence suggests 7-keto-DHEA might increase basal metabolism.

In obese patients, 7-keto-DHEA can significantly increase the thyroid hormone triiodothyronine (T3) when used over four weeks.⁴⁶ This effect on thyroid function may positively influence metabolism⁴⁷, helping patients reduce body weight and body fat. In fact, one clinical study seems to support the hypothesis that the supplement can enhance weight loss.

Thirty overweight adults were randomized into a prospective, double-blind, placebo controlled eight-week study.⁴⁸ Fifteen subjects received 100 mg 7-Keto DHEA twice per day whereas the other 15 subjects received a matching placebo. All subjects exercised three times per week, 60 minutes per session of cross-training (aerobic and anaerobic) under the supervision of an exercise physiologist. The exercise plus 7-Keto DHEA group lost a significant amount of body weight as compared with the exercise plus placebo group.

When analyzed per a four-week interval, the 7-Keto DHEA group lost 3.17 lbs per interval, whereas placebo lost 1.09 lbs. In terms of actual body composition changes, the exercise plus 7-Keto DHEA group lost 1.8 percent body fat as compared to 0.57 percent for the placebo group. When viewed as a change in body fat per four-week interval, the 7-Keto DHEA group lost 0.89 percent body fat per interval as compared to 0.29 percent for the placebo.

In a later randomized, double-blind, placebo-controlled, crossover trial⁴⁹, 7-Keto DHEA was tested in overweight adults maintained on a calorie-restricted diet to determine efficacy in increasing the resting metabolic rate (RMR). The results were that RMR increased significantly by 1.4 percent in the 7-Keto DHEA group, whereas RMR decreased by 3.9 percent in the placebo group. In this study, 7-Keto reversed the decrease in RMR normally associated with dieting and was generally well tolerated with no serious adverse events.

7-Keto: Cognitive Function
Research has indicated that that DHEA administration might be beneficial in terms of neuroprotection against age-related loss of brain functions like learning and memory.⁵⁰ Furthermore, DHEA showed insignificant effects on both learning/memory ability in aging rats.⁵¹ Higher DHEA-S levels are also independently and favorably associated with executive function, concentration, and working memory in humans.⁵² In addition, other research suggests that 7-keto-DHEA improves chemically-induced and age-related memory impairment.⁵³

7-Keto: Immune Function
7-keto DHEA has also been studied for its potential immune-boosting properties. This includes immunomodulatory effects by stimulating interleukin-2 production by human lymphocytes in-vitro.⁵⁴ Researchers think that it may also stimulate the activity and effectiveness of T-lymphocytes. These T-lymphocytes may in turn stimulate additional immune system functions.⁵⁵ Studies based on these observations suggest that 7-keto DHEA may have a future as an important immune system enhancer.^56,57 Thus, 7-keto DHEA could prove to be therapeutically useful in a wide range of conditions. Studies suggest that DHEA may reduce the replication of certain types of viruses.⁵⁸

References

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42. Genazzani AD, Stomati M, Bernardi F, et al. Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids. Fertil Steril 2003;80:1495–501.
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Resveratrol Background
Before jumping into a discussion about the fascinating human research, however, let’s take a moment to review just what resveratrol is, in case you’re unfamiliar with it. Resveratrol is a type of natural phenol by several plants in response to injury or attack by pathogens.^3,4 These plants include grapes, peanuts⁵ and Japanese Knotweed (Polygonum cuspidatum).⁶ Resveratrol helps provide protection to the plants, at least in part, due to its demonstrated antioxidant properties.⁷ These antioxidant properties benefit humans too, as shown in research where resveratrol provided a direct antioxidant effect against free radicals, and facilitated an increase in vitamin E⁸—another powerful antioxidant.

There are two primary isomers (i.e. two forms) of resveratrol, trans- and cis-. To be clear, trans-resveratrol has been unequivocally shown to have much greater activity than cis-resveratrol.⁹ Consequently, when purchasing a resveratrol product, make sure to check the supplement facts panel to verify that the product contains trans-resveratrol. If just”resveratrol” is listed, without the trans-designation, or if cis-resveratrol is listed, you would be better off choosing a different product that lists trans-resveratrol. In any case, for ease of reading, I will drop references to trans– in the rest of this article, although it can be assumed that any mention of resveratrol will actually refer to trans-resveratrol.

Cardiovascular Health
As its first claim to fame, resveratrol has been found to have activity that may have protective effects on the cardiovascular system. In both test-tube and animal research, resveratrol has been shown to inhibit platelet aggregation (i.e. the clumping together of blood platelets). This has value since excessive or inappropriate aggregation of platelets can lead to formation of blood clots and subsequent blockages in blood vessels that result in insufficient blood flow, heart attack or stroke.¹⁰ Resveratrol can also promote vasodilation (a relaxed and expanded state of the artery that accommodates increased blood flow) by enhancing the production of a naturally occurring substance in the body called nitric oxide.¹¹

More importantly, human clinical research¹² has demonstrated that 100 mg/day of resveratrol significantly reduced arterial stiffness (a major indicator of atherosclerosis) compared to placebo, and also lowered systolic blood pressure by 5.5 points in patients with type 2 diabetes. Another human study,¹³ which used a much higher dose (2.3 g) in older adults, found that resveratrol not only improved vascular function more than placebo, but also increased the number of mitochondria.those parts of the cells that help to generate energy for our body! Another interesting cardiovascular benefit is resveratrol’s effect on Apolipoprotein B (ApoB), a primary component of many lipoproteins such as LDL (the gbad cholesterolh) that are involved in atherosclerosis and cardiovascular disease. In human clinical research¹⁴ on overweight or obese individuals with mild hypertriglyceridemia, 1000 mg/day of resveratrol for one week followed by 2000 mg/day for two weeks reduced ApoB production rate by an impressive 22 percent. In addition, flow-mediated dilatation (a measure of arterial circulation and endothelial function) was increased in human studies^15,16,17 where 10 mg to 270 mg/day of resveratrol was given. In one of the studies,¹⁸ LDL cholesterol levels were also significantly decreased.

Inflammation
In addition to showing anti-inflammatory effects in in-vitro and animal studies, resveratrol has also been shown to comprehensively suppress oxidative and inflammatory stress with as little as 40 mg/day in normal human subjects.¹⁹ This included the reduction of inflammatory markers such as TNF-alpha, IL-6, and C-reactive protein, with no changes in the placebo group. Similarly, in postmenopausal women with osteoarthritis pain, 75 mg of resveratrol twice daily significantly reduced pain and improved total well-being.²⁰

Ulcerative colitis (UC), a chronic inflammatory bowel disease, has also responded to treatment with resveratrol. In one study²¹ with 56 UC patients, those receiving 500 mg/day of resveratrol had significant symptom improvement, reduced malondialdehyde (a highly reactive oxidative stress compound), and increased superoxide dismutase (SOD), and total antioxidant capacity. In another human study²² with 50 UC patients, 500 mg/day of resveratrol also reduced the activity of inflammatory compounds, including TNF-α, hs-CRP, and activity of NF-κB. Furthermore, in a study²³ of firefighters, supplementation with 100 mg/day resveratrol for 90 days, plasma biomarkers of inflammation were reduced after a physical fitness test, including IL-6 and TNF-α. This adds further credence to resveratrol’s anti-inflammatory effects.

Immune Health/Breast Cancer Prevention
Resveratrol’s effect on immune health can be as fundamental as increasing certain circulating immune cells, or as profound at reducing the risk of breast cancer. For example, human research²⁴ was conducted to assess the effects of repeated doses of resveratrol (1000 mg/day for 28 days) on circulating immune cells in healthy individuals. The results were that resveratrol was safe and well tolerated and was associated with significant increases in the numbers of circulating gamma delta T cells (functioning as a first line of defense and a bridge between innate and adaptive responses) and regulatory T cells—demonstrating that resveratrol has clear biological effects on human circulating immune cells.

With regard to breast cancer prevention, resveratrol may help in a couple of ways. First, resveratrol has been shown to have a dose-dependent effect on reducing the formation of mammary tumors in-vitro as a result of down-regulating DNA methyltransferases. To see if it had a similar effect in humans, a study²⁵ was conducted in which 39 adult women at increased breast cancer risk received a placebo, 5 or 50 mg of resveratrol twice daily for 12 weeks. Results were that there was indeed decrease in methylation of the tumor suppressor gene with increasing levels of resveratrol (P = .047).

In another study²⁶ of 34 overweight, postmenopausal women (BMI ≥ 25 kg/m2), the clinical effect of resveratrol on systemic sex steroid hormones were investigated, since high estrogen levels may contribute to breast cancer. The subjects received 1 g of resveratrol daily for 12 weeks. The results were that resveratrol supplementation led to an average of 73 percent increase in urinary 2-hydroxyestrone (the “good estrogen”) levels leading to a favorable change in estrogen ratios that are less conducive to the development of breast cancer. This research demonstrated that among overweight and obese postmenopausal women, a daily 1 g dose of resveratrol has favorable effects on estrogen metabolism.

Muscle Health
In a 12-week study,²⁷ older men and women (aged 65.80 years) exercised and took either a placebo or 500 mg/day of resveratrol to determine if resveratrol would have additive effects to those of exercise. Results showed that exercise added to resveratrol treatment increased the number of mitochondria, and improved muscle fatigue resistance more than placebo and exercise treatments. In addition, subjects treated with resveratrol had an increase in muscular torque and power after training, whereas exercise did not increase these parameters in the placebo-treated older subjects. Furthermore, exercise combined with resveratrol significantly improved muscle fiber. Together, these data suggest that resveratrol combined with exercise might provide a better approach for reversing sarcopenia than exercise alone.

Cognitive Health
Research suggests that resveratrol may have cognitive health benefits in people with and without dementia. For example, the ongoing dysfunction of small blood vessels in patients with type 2 diabetes mellitus (T2DM) may impair the ability of cerebral vessels to supply blood to various brain regions, thereby increasing risks of dementia. To determine if resveratrol could benefit cerebral circulation, a study²⁸ was conducted in which 36 dementia-free, non-insulin dependent T2DM older adults (49–78 years old) consumed single doses of resveratrol (0, 75, 150, and 300 mg) at weekly intervals. Results were that 75–300 mg of resveratrol enhanced vasodilator responsiveness in cerebral vessels.

In another study,²⁹ 80 post-menopausal women aged 45–85 years received resveratrol or placebo for 14 weeks to examine the effect on cognitive performance and other parameters. Results were that compared to placebo, significant improvements were observed in the performance of cognitive tasks in the domain of verbal memory (p = 0.041) and in overall cognitive performance (p = 0.020). Mood also tended to improve in multiple measures. These results indicate that regular consumption of a modest dose of resveratrol can enhance both cerebrovascular function and cognition in post-menopausal women, potentially reducing their heightened risk of accelerated cognitive decline and offering a promising therapeutic treatment for menopause-related cognitive decline.

To test³⁰ whether supplementation of resveratrol (200 mg/ day for 26 weeks) would enhance memory performance in older adults, 23 healthy overweight older individuals were pairwise matched to 23 participants that received placebo (total n = 46, 18 females, 50–75 years). Results showed a significant effect of resveratrol on retention of words over 30 min compared with placebo (p = 0.038), significant increases in hippocampal functional connectivity, decreases in glycated hemoglobin (HbA1c) and body fat, and increases in leptin compared with placebo (all p < 0.05). This study provides initial evidence that supplementary resveratrol improves memory performance in association with improved glucose metabolism in older adults, providing a basis for helping to maintain brain health during aging.

To determine the effects of oral resveratrol on localized cerebral blood flow, a study³¹ was conducted with which 22 healthy human adults received placebo and two doses (250 and 500 mg) of resveratrol in counterbalanced order on separate days. After a 45-min resting absorption period, the participants performed a selection of cognitive tasks. Resveratrol administration resulted in dose-dependent increases in cerebral blood flow during task performance, and enhanced oxygen extraction. These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables.

Finally, a clinical study³² was conducted to determine if up to 1 g of resveratrol twice daily could benefit Alzheimer’s disease (AD) patients. The results demonstrated that resveratrol decreased CSF MMP9 (a biomarker for confirmed AD), modulates neuro-inflammation, and induces adaptive immunity— suggesting that resveratrol may be a viable target for treatment or prevention of neurodegenerative disorders.

Weight Loss
One of the reasons that resveratrol has received widespread interest is because of its ability to mimic effects of calorie restriction. To gain more insight into this effect on adipose tissue, a study³³ was conducted in which healthy obese subjects were supplemented with 150 mg/day of resveratrol or placebo for 30 days. Results showed that resveratrol significantly decreased the size of adipocytes (fat cells), with a shift toward reducing the proportion of large and very-large adipocytes and an increase in small adipocytes. Furthermore, lysosomal/phagosomal pathway and transcription factor EB were up-regulated reflecting an alternative pathway of lipid breakdown by autophagy.

Similarly,³⁴ T2DM patients received 3 g resveratrol or placebo daily for 12 weeks. Results were that there was a significant increase in both SIRT1 expression and resting metabolic rate compared with the placebo group. In patients with T2DM, treatment with resveratrol helped regulate energy expenditure, suggesting that resveratrol may have beneficial exercise-mimetic effects.

Again,³⁵ healthy, obese subjects were treated with placebo and 150 mg/day resveratrol for 30 days. The results were that resveratrol increased SIRT1 and improved the muscle’s use of fatty acids as an energy fuel, demonstrating that 30 days of resveratrol supplementation induces metabolic changes in obese humans, mimicking the effects of calorie restriction. Given these results, one might think that resveratrol may aid in weight loss—and indeed this has been shown to be the case in clinical research.

Orlistat is an over-the-counter drug (also known as Alli®) designed to treat obesity by reducing the absorption of fats from the human diet. A study³⁶ was conducted to evaluate the efficacy of combining orlistat with resveratrol in 84 obese subjects over a 6-month period. The subjects consumed a diet with 500 fewer calories than their usual diet for two weeks, and were randomly assigned to four groups, placebo, resveratrol, orlistat, or the O-R combination, and they consumed the energy-reduced diet for 6-months. Results were significant weight loss of 15 lbs in the O-R group compared with 7.7 lbs in the placebo group. Significant decreases in BMI, waist circumference, fat mass, triglycerides, leptin, and leptin/adiponectin ratio were observed with the O-R combination, indicating that it was the most effective weight loss treatment.

In another study,³⁷ 24 patients with metabolic syndrome received resveratrol (500 mg) three times per day before meals for 90 days. Resveratrol administration resulted in significant differences in total weight (P=0.007), body mass index (BMI) (P=0.006), fat mass (P=0.001), and waist circumference (P=0.004). In conclusion, administration of resveratrol significantly decreased weight, BMI, and fat mass.

Blood Sugar/Insulin Resistance
A study³⁸ was conducted using 480 mg/day of resveratrol or placebo for four weeks on 43 patients with diabetes who also had chronic periodontitis (i.e. gum disease). Results were that serum levels of fasting insulin and insulin resistance were significantly lower in the resveratrol group compared with control group. With regard to periodontal disease, there was also a significant difference in the gum pocket depth between intervention and control groups with resveratrol. The researchers recommended that resveratrol supplementation might be beneficial as adjuvant therapy along with non-surgical periodontal treatment in insulin resistance and improving periodontal status among patients with diabetes with periodontal disease.

Another human clinical trial³⁹ was conducted in 32 over-weight, older adults (average age: 73 years). Participants received placebo, 300 mg/day of resveratrol, or 1000 mg/day of resveratrol for 90 days. Results were that, compared to placebo, glucose levels were significantly lower at after treatment among participants receiving either dose of resveratrol (P<0.05), and were well tolerated.

In this study,⁴⁰ 62 patients with T2DM received either an oral hypoglycemic medication, or an oral hypoglycemic medication along with 250 mg/day of resveratrol. Results were that supplementation with resveratrol for three months significantly improved the mean hemoglobin A1c (P<0.05), a measure of long-term glucose control, systolic blood pressure (P<0.05), total cholesterol (P<0.05), and total protein (P<0.05) in T2DM. The researchers concluded that oral supplementation with resveratrol was effective in improving glycemic control and may be a potential adjuvant for the treatment and management of diabetes.

In a pilot study,⁴¹ subjects with impaired glucose tolerance (aged 72 ± 3 years) received 1, 1.5, or 2 g/day of resveratrol for four weeks. After four weeks of resveratrol supplementation, results showed that post-meal (P=0.003) and 3-hour glucose levels (P=0.001) declined. Researchers concluded that, at doses between 1 and 2 g/day, resveratrol improves insulin sensitivity and post-meal plasma glucose in subjects with impaired glucose tolerance. Likewise, in a 4-week study,⁴² T2DM patients received 10 mg/day resveratrol or a placebo. Results showed that, after the fourth week, resveratrol significantly improved insulin sensitivity, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin-signaling pathway.

Non-Alcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of fat in the liver of people who drink little or no alcohol. Unfortunately, NAFLD is common—with easily one-third of all American adults being affected⁴³—and often causes no signs and symptoms, and sometimes no complications. In more serious cases, however, the fat that accumulates in NAFLD can cause liver inflammation and scarring.⁴⁴ In addition, NAFLD is usually associated with insulin resistance, central obesity, reduced glucose tolerance, T2DM and high triglyceride levels.

In a clinical study,⁴⁵ 50 NAFLD patients received either a 500 mg/day of resveratrol or a placebo for 12 weeks. Both groups were advised to follow an energy-balanced diet and physical activity recommendations. Results were that resveratrol supplementation reduced alanine aminotransferase (a marker for NAFLD) and hepatic steatosis (fatty liver) significantly more than placebo (P<0E05).

In another study,⁴⁶ 60 NAFLD patients received two 150 mg resveratrol capsules twice daily for three months. Results were that, compared with the placebo group, resveratrol significantly decreased aspartate aminotransferase, glucose and low-density lipoprotein cholesterol (P.0.001) alanine aminotransferase, total cholesterol (P=0.002), and insulin resistance (P=0.016). The researchers concluded that resveratrol supplementation might benefit patients with NAFLD.

Other Resveratrol Benefits
In addition to the aforementioned applications for resveratrol, there are additional benefits for this nutraceutical as well. Two such benefits are related to bone health, and for those who are smokers.

In a clinical study,⁴⁷ 66 middle-aged, obese subjects with metabolic syndrome (average age: 49.3 } 6.3 years) received oral treatment with 1,000 mg or 150 mg of resveratrol, or a placebo daily for 16 weeks to assess changes in the bone turnover marker bone alkaline phosphatase (BAP), and bone mineral density (BMD). Results were that BAP increased dose dependently with resveratrol (P<0.001), compared with placebo. Lumbar spine trabecular volumetric bone mineral density also increased dose dependently with resveratrol (P=0.036), with a significant increase of 2.6 percent in the 1,000 mg resveratrol group compared with placebo (P=0.043). In addition, changes in BAP and bone mineral density were positively correlated (P=0.027).

Smokers typically experience a state of low-grade systemic inflammation and oxidant-antioxidant imbalance. To determine whether resveratrol has beneficial effects on markers of inflammation and oxidative stress, a study⁴⁸ was conducted with 50 healthy adult smokers who alternatively were given 500 mg/ day of resveratrol and placebo. Results were that resveratrol significantly reduced the inflammatory marker C-reactive protein (CRP), triglyceride concentrations, and increased Total Antioxidant Status (TAS) values. The researchers concluded that, because resveratrol has anti-inflammatory, anti-oxidant, and hypotriglyceridemic effects, its supplementation might beneficially affect the increased cardiovascular risk of healthy smokers.

Improving The Bioavailability And Efficacy Of Resveratrol

Now that we’ve reviewed some of the many benefits associated with resveratrol supplementation, let’s briefly consider ways to improve the bioavailability and efficacy of this valuable nutraceutical. First, take resveratrol on an empty stomach. The reason for this recommendation is a study showing that the absorption rate of resveratrol following an oral 400 mg single dose was significantly delayed by the presence of food.⁴⁹

Second, resveratrol may work better when taken together with pterostilbene (a related antioxidant) and quercetin (a flavonoid). In this study,⁵⁰ the antioxidant activities of resveratrol, pterostilbene and quercetin, and the effect of their combination were investigated in human blood cells in-vitro. When used together, the combination protected the blood cells against destruction and against depletion of the important antioxidant, glutathione. Also, the combination of resveratrol with quercetin or pterostilbene synergistically inhibited oxidative injury of membrane lipids. These protective effects may partially explain the health benefit of these bioactive micro-components when together in the diet.

Conclusion
The value of supplementation with resveratrol has moved beyond the “French paradox” and the activation of the SIRT 1 gene, associated with longevity. Human clinical research has demonstrated efficacy of resveratrol for inflammation, immune health/breast cancer prevention, muscle health, cognitive health, weight loss, blood sugar/insulin resistance, non-alcoholic fatty liver disease, and more.

Endnotes

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